Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
To confirm the safety of BIBF 1120 at a dose level up to 200 mg x 2/day (i.e., overseas recommended Phase III dose for combination treatment) with standard therapy of docetaxel (60 mg/m2 and 75 mg/m2) in Japanese advanced non small cell lung cancer (NSCLC) patients with stage IIIB/IV or recurrent after failure of first line chemotherapy and to determine the recommended dose for the Phase II trial.
Interventions
DRUGBIBF 1120 M + docetaxel M
BIBF 1120 Medium dose bid + docetaxel 60 mg/m2
DRUGBIBF 1120 M + docetaxel H
BIBF 1120 Medium dose bid + docetaxel 75mg/m2
DRUGBIBF 1120 H + docetaxel H
BIBF 1120 HIgh dose bid + docetaxel 75 mg/m2
DRUGBIBF 1120 L + docetaxel M
BIBF 1120 Low dose bid + docetaxel 60 mg/m2
DRUGBIBF 1120 H + docetaxel M
BIBF 1120 HIgh dose bid + docetaxel 60 mg/m2
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically/cytologically confirmed, locally advanced/metastatic NSCLC of stage IIIB/IV or recurrent NSCLC (all histologies. Existence or nonexistence of measurable lesion according to RECIST is no object.) 2. Patients with one prior chemotherapy regimen including platinum-containing drug. In case of recurrent disease, one additional prior regimen is allowed for adjuvant and/or neoadjuvant therapy. However monotherapy of EGFR-TKI (i.e. erlotinib/Tarceva® and gefitinib/Iressa®) is not counted as 'one regimen'. 3. Male or female patients age \>=20 years and =\<74 years at the enrolment. 4. Life expectancy of at least three (3) months after the start of administration of the investigational drug. 5. Eastern Cooperative Oncology Group (ECOG) \[R01-0787\] performance Score 0 or 1. 6. Patients retaining a significant physiological compensatory function and patients with sufficient baseline organ function as follows: * Haemoglobin count more than 9.0g/dL * Absolute neutrophil count more than 1500/mm3 * Platelet count more than 100 000/mm3 * Serum creatinine less than or equal to1.5x upper limit of normal range at the investigator site * Aspartate aminotransferase (AST) and / or alanine aminotransferase (ALT) less than or equal to 1.5x upper limit of normal range at the investigator site (It is the same if patients have liver metastases) * PaO2 or SpO2 more than 60torr or 92% 7. Written informed consent that is consistent with ICH-GCP guidelines.
Exclusion criteria
1. Patients who have received chemotherapy (including other investigational drug), hormonal therapy and immune therapy =\<4 weeks prior to registration or who have not recovered from side effects of such therapy. 2. Patients who have received radiotherapy =\<4 weeks (limited field (e.g brain or bone metastasis) radiation =\<2 weeks) prior to registration. 3. Patients who have active brain metastases. (Patients who have no symptoms and is not needed to receive therapy in the registration may participate in this trial) 4. Patients with active double cancer. (Patients who have skin cancer that is not malignant melanoma and carcinoma in situ of uterine cervix may participate in this trial) 5. Patients with distinct / suspected pulmonary fibrosis or interstitial lung disease by the chest radiographic findings, or patients with a previous history of. 6. History of clinically significant haemoptysis within the past 3 months (more than one tea spoon of fresh blood per day) 7. Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except for chronic low-dose therapy with acetylsalicylic acid =\<325 mg per day) 8. History of major thrombotic or clinically relevant major bleeding event in the past 6 months prior to registration. 9. Known inherited predisposition to bleeding or thrombosis. 10. Significant cardiovascular diseases. (i.e. hypertension not controlled by medical therapy, unstable angina, history of myocardial infarction within the past 6 months, congestive heart failure \> NYHA II, serious cardiac arrhythmia, pericardial effusion) 11. Significant weight loss (\> 10 %) within the past 6 weeks prior to registration in the this trial 12. Current peripheral neuropathy \>= CTCAE grade 2 except due to trauma. 13. Accumulation of coelomic fluid (e.g. pleural effusion, ascites fluid, cardiac effusion) requiring treatment 14. Major injuries and/or surgery within the past 10 days prior to registration with incomplete wound healing. 15. Serious infections requiring systemic antibiotic (e.g antiviral, antimicrobial, antifungal) therapy. 16. Decompensated diabetes mellitus or other contraindication to high dose corticosteroid therapy. 17. Gastrointestinal disorders or abnormalities (e.g Crohn's disease, Colitis ulcerosa and extensive gastrectomy) that would interfere with absorption of the study drug. 18. Patients with difficulty in swallowing study medication 19. Patients with positive HBs antigen, HCV antibody, or HIV antibody test 20. Serious illness or concomitant non-oncological disease such as neurologic-, psychiatric-, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or investigational drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the trial. 21. Patients who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during the trial and for at least 12 months after end of active therapy 22. Female patients who are pregnant, breast feeding and may become pregnant. 23. Patients who have or is suspected of having active alcohol or drug abuse. 24. Patient with clinically meaningful drug hypersensitivities. 25. Patients with auto immune disease. 26. Patients unable to comply with the protocol. 27. Other patients judged ineligible for enrolment in the study by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Dose Limited Toxicity in Combination Therapy of Nintedanib and Docetaxel | During the first treatment course, up to 3 weeks | Number of participants experienced Dose Limited Toxicity (DLT) in combination therapy of nintedanib and docetaxel. Maximum tolerated dose (MTD) of nintedanib combination with docetaxel were to be determined separately in the patient groups of body surface area (BSA) \<1.5 m2 and BSA ≥1.5 m2. The MTD were to be determined as a combination of a dose equal to or less than 200 mg b.i.d. of nintedanib and 60 mg/m2 and 75 mg/m2 every 3 weeks of docetaxel at which either 0 out of 3, 1 out of 6, or 2 out of 6 patients experienced DLT. |
| Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Between the first administration of docetaxel and 28 days after last administration of docetaxel and/or nintedanib, up to 1367 days | Number of participants with adverse events according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 for all courses. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Pre-treatment, every 6 weeks from treatment course 3, end of treatment (up to 1367 days) | For participants with known date of progression or death (of any cause): PFS \[days\] = earlier of date of progression or death - date the study treatment started + 1. For participants known to be alive without progression by the end of trial or follow-up visit: PFS (censored) \[days\] = date of last imaging when the participant is known to be progression-free and alive - date the study treatment started + 1. Progression is assessed according to RECIST version 1.0. |
| Time to Treatment Failure (TTF) | Pre-treatment, every 6 weeks from treatment course 3, end of treatment (up to 1367 days) | For participants with known date of discontinuation of the study treatment (or progression \[not necessarily confirmed by tumour imaging; can also be based on any clinical sign of tumour progression\] or death): TTF \[days\] = earlier of date of discontinuation of the study treatment, progression, or death - date the study treatment started + 1. For participants known to be alive without progression by the end of trial or follow-up visit: TTF (censored) \[days\] = date when the patient is known to be progression-free and alive - date the study treatment started + 1. Progression is assessed according to RECIST version 1.0. |
| Clinical Relevant Abnormalities in Laboratory Parameters | Between the first administration of docetaxel and 28 days after last administration of docetaxel and/or nintedanib, up to 1367 days | Number of participants with clinically relevant abnormalities in laboratory parameters reported as adverse events |
| AUC0-inf of Nintedanib in Course 1 | -0:05 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 7h, 10h and 23:55h after drug administration in course 1 | AUC0-inf (area under the plasma concentration-time curve over the time interval from 0 extrapolated to infinity) after the first administration of nintedanib in course 1 |
| Objective Tumor Response | Pre-treatment, every 6 weeks from treatment course 3, end of treatment (up to 1367 days) | Number of participants with objective response defined as complete response (CR) or partial response (PR) according to the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 |
| AUC0-inf of Docetaxel in Course 1 | -0:05h before drug administration and 1h, 1.5h, 2h, 3h, 4h, 7h, 23:55h and 47:55h after drug administration | AUC0-inf (area under the plasma concentration-time curve over the time interval from 0 extrapolated to infinity) after the first administration of docetaxel in course 1 |
| Cmax of Docetaxel in Course 1 | -0:05h before drug administration and 1h, 1.5h, 2h, 3h, 4h, 7h, 23:55h and 47:55h after drug administration | Cmax (maximum measured plasma concentration) after the first administration of docetaxel in course 1 |
| AUC0-inf of Docetaxel in Course 2 | -0:05h before drug administration and 1h, 1.5h, 2h, 3h, 4h, 7h, 23:55h and 47:55h after drug administration | AUC0-inf (area under the plasma concentration-time curve over the time interval from 0 extrapolated to infinity) after the first administration of docetaxel in course 2. Docetaxel 50 mg/m2 patients were assigned to Docetaxel 60 mg/m2 in Cycle 1, but the dose was reduced to 50 mg/m2 in Cycle 2 as defined in the Clinical Trial Protocol. |
| Cmax of Docetaxel in Course 2 | -0:05h before drug administration and 1h, 1.5h, 2h, 3h, 4h, 7h, 23:55h and 47:55h after drug administration | Cmax (maximum measured plasma concentration) after the first administration of docetaxel in course 2. Docetaxel 50 mg/m2 patients were assigned to Docetaxel 60 mg/m2 in Cycle 1, but the dose was reduced to 50 mg/m2 in Cycle 2 as defined in the Clinical Trial Protocol. |
| Cmax of Nintedanib in Course 1 | -0:05h before drug administration and 1h, 2h, 3h, 4h, 6h, 7h, 10h and 23:55h after drug administration in course 1 | Cmax (maximum measured plasma concentration) after the first administration of nintedanib in course 1 |
| Disease Control | Pre-treatment, every 6 weeks from treatment course 3, end of treatment (up to 1367 days) | Number of participants with disease control, defined as complete response (CR) or partial response (PR) or stable disease (SD) according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 |
Countries
Japan
Participant flow
Recruitment details
43 patients entered.1 patient was replaced because he did not take any nintedanib(Nin) due to new brain metastasis after completion of first administration of docetaxel. Accordingly,42 patients treated with at least 1 dose of Nin in combination with docetaxel.Patients started mono therapy phase after discontinued from combination therapy phase .
Pre-assignment details
In case a patient had to discontinue docetaxel for reasons other than progression disease, the patient could continue therapy with nintedanib if the patient had been treated with combination therapy with docetaxel during at least 4 treatment courses.
Participants by arm
| Arm | Count |
|---|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 Patients administered a soft gelatin capsule of nintedanib 100 mg, orally, twice daily (b.i.d.) from day 2 in combination with docetaxel 60 mg/m2 injection once every three weeks administered via intravenous infusion over one hour. Nintedanib was not taken when docetaxel was administered. | 3 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) Patients with body surface area (BSA) \<1.5 m\^2 administered a soft gelatin capsule of nintedanib 150 mg, orally, b.i.d. from day 2 in combination with docetaxel 60 mg/m2, injection once every three weeks administered via intravenous infusion over one hour. Nintedanib was not taken when docetaxel was administered. | 7 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) Patients with body surface area ≥1.5 m\^2 administered a soft gelatin capsule of nintedanib 150 mg, orally, b.i.d. from day 2 in combination with docetaxel 60 mg/m2, injection once every three weeks administered via intravenous infusion over one hour. Nintedanib was not taken when docetaxel was administered. | 3 |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) Patients with body surface area \<1.5 m\^2 administered a soft gelatin capsule of nintedanib 150 mg, orally, b.i.d. from day 2 in combination with docetaxel 75 mg/m2 injection once every three weeks administered via intravenous infusion over one hour. Nintedanib was not taken when docetaxel was administered. | 6 |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) Patients with body surface area ≥1.5 m\^2 administered a soft gelatin capsule of nintedanib 150 mg, orally, b.i.d. from day 2 in combination with docetaxel 75 mg/m2 injection once every three weeks administered via intravenous infusion over one hour. Nintedanib was not taken when docetaxel was administered. | 7 |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) Patients with body surface area \<1.5 m\^2 administered a soft gelatin capsule of nintedanib 200 mg, orally, b.i.d. from day 2 in combination with docetaxel 60 mg/m2 injection once every three weeks administered via intravenous infusion over one hour. Nintedanib was not taken when docetaxel was administered. | 3 |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) Patients with body surface area ≥1.5 m\^2 administered a soft gelatin capsule of nintedanib 200 mg, orally, b.i.d. from day 2 in combination with docetaxel 60 mg/m2 injection once every three weeks administered via intravenous infusion over one hour. Nintedanib was not taken when docetaxel was administered. | 7 |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) Patients with body surface area ≥1.5 m\^2 administered a soft gelatin capsule of nintedanib 200 mg, orally, b.i.d. from day 2 in combination with docetaxel 75 mg/m2 injection once every three weeks administered via intravenous infusion over one hour. Nintedanib was not taken when docetaxel was administered. | 6 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Combination Therapy Phase | Adverse Event | 0 | 2 | 0 | 2 | 2 | 0 | 3 | 2 |
| Combination Therapy Phase | Dose limiting toxicity | 0 | 1 | 0 | 1 | 1 | 2 | 2 | 1 |
| Combination Therapy Phase | Not treated | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Combination Therapy Phase | Other reason not defined above | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 |
| Combination Therapy Phase | Progressive disease | 2 | 3 | 3 | 3 | 3 | 1 | 1 | 1 |
| Combination Therapy Phase | Withdrawal by Subject | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
| Mono Therapy Phase | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Mono Therapy Phase | Progressive disease | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 3 |
| Mono Therapy Phase | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Nintedanib 100 mg + Docetaxel 60 mg/m2 | Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.0 years | 68.0 years | 64.0 years | 65.0 years | 63.0 years | 62.0 years | 64.0 years | 61.5 years | 63.5 years |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 0 Participants | 4 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 13 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 3 Participants | 2 Participants | 6 Participants | 0 Participants | 6 Participants | 6 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 7 / 7 | 3 / 3 | 6 / 6 | 7 / 7 | 3 / 3 | 7 / 7 | 6 / 6 |
| serious Total, serious adverse events | 1 / 3 | 4 / 7 | 0 / 3 | 2 / 6 | 4 / 7 | 0 / 3 | 3 / 7 | 1 / 6 |
Outcome results
Primary
Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses
Number of participants with adverse events according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 for all courses. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
Time frame: Between the first administration of docetaxel and 28 days after last administration of docetaxel and/or nintedanib, up to 1367 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 3 | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 4 | 3 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 2 | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 1 | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 5 | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 1 | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 2 | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 3 | 1 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 4 | 6 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 5 | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 1 | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 5 | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 4 | 1 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 2 | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 3 | 2 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 3 | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 2 | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 4 | 5 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 5 | 1 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 1 | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 3 | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 1 | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 2 | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 4 | 7 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 5 | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 3 | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 4 | 3 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 2 | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 1 | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 5 | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 3 | 1 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 1 | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 2 | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 5 | 1 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 4 | 5 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 5 | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 4 | 6 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 1 | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 3 | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses | Grade 2 | 0 Participants |
Primary
Number of Participants Who Experienced Dose Limited Toxicity in Combination Therapy of Nintedanib and Docetaxel
Number of participants experienced Dose Limited Toxicity (DLT) in combination therapy of nintedanib and docetaxel. Maximum tolerated dose (MTD) of nintedanib combination with docetaxel were to be determined separately in the patient groups of body surface area (BSA) \<1.5 m2 and BSA ≥1.5 m2. The MTD were to be determined as a combination of a dose equal to or less than 200 mg b.i.d. of nintedanib and 60 mg/m2 and 75 mg/m2 every 3 weeks of docetaxel at which either 0 out of 3, 1 out of 6, or 2 out of 6 patients experienced DLT.
Time frame: During the first treatment course, up to 3 weeks
Population: Treated set (Patients eligible for DLT confirmation)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Number of Participants Who Experienced Dose Limited Toxicity in Combination Therapy of Nintedanib and Docetaxel | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Number of Participants Who Experienced Dose Limited Toxicity in Combination Therapy of Nintedanib and Docetaxel | 2 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Number of Participants Who Experienced Dose Limited Toxicity in Combination Therapy of Nintedanib and Docetaxel | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Number of Participants Who Experienced Dose Limited Toxicity in Combination Therapy of Nintedanib and Docetaxel | 1 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Number of Participants Who Experienced Dose Limited Toxicity in Combination Therapy of Nintedanib and Docetaxel | 2 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Number of Participants Who Experienced Dose Limited Toxicity in Combination Therapy of Nintedanib and Docetaxel | 3 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Number of Participants Who Experienced Dose Limited Toxicity in Combination Therapy of Nintedanib and Docetaxel | 2 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Number of Participants Who Experienced Dose Limited Toxicity in Combination Therapy of Nintedanib and Docetaxel | 2 Participants |
Secondary
AUC0-inf of Docetaxel in Course 1
AUC0-inf (area under the plasma concentration-time curve over the time interval from 0 extrapolated to infinity) after the first administration of docetaxel in course 1
Time frame: -0:05h before drug administration and 1h, 1.5h, 2h, 3h, 4h, 7h, 23:55h and 47:55h after drug administration
Population: Treated set (1 patient was replaced after completion of first administration of docetaxel and before any nintedanib intake. Pharmacokinetic (PK) sampling of docetaxel for this patient was done and included in PK analysis.)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | AUC0-inf of Docetaxel in Course 1 | 3270 ng*h/mL | Geometric Coefficient of Variation 35.6 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | AUC0-inf of Docetaxel in Course 1 | 3810 ng*h/mL | Geometric Coefficient of Variation 22.7 |
Secondary
AUC0-inf of Docetaxel in Course 2
AUC0-inf (area under the plasma concentration-time curve over the time interval from 0 extrapolated to infinity) after the first administration of docetaxel in course 2. Docetaxel 50 mg/m2 patients were assigned to Docetaxel 60 mg/m2 in Cycle 1, but the dose was reduced to 50 mg/m2 in Cycle 2 as defined in the Clinical Trial Protocol.
Time frame: -0:05h before drug administration and 1h, 1.5h, 2h, 3h, 4h, 7h, 23:55h and 47:55h after drug administration
Population: Treated set (AUC0-inf could not be calculated in 1 patient because the elimination phase was not observed in plasma concentration-time profile in this patient.)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | AUC0-inf of Docetaxel in Course 2 | 2320 ng*h/mL | Geometric Coefficient of Variation 14.9 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | AUC0-inf of Docetaxel in Course 2 | 3750 ng*h/mL | Geometric Coefficient of Variation 31.1 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | AUC0-inf of Docetaxel in Course 2 | 4270 ng*h/mL | Geometric Coefficient of Variation 34.2 |
Secondary
AUC0-inf of Nintedanib in Course 1
AUC0-inf (area under the plasma concentration-time curve over the time interval from 0 extrapolated to infinity) after the first administration of nintedanib in course 1
Time frame: -0:05 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 7h, 10h and 23:55h after drug administration in course 1
Population: Treated set (AUC0-inf could not be calculated in 5 patients because the elimination phase was not observed in plasma concentration-time profiles in these patients.)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | AUC0-inf of Nintedanib in Course 1 | 169 ng*h/mL | Geometric Coefficient of Variation 56.1 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | AUC0-inf of Nintedanib in Course 1 | 260 ng*h/mL | Geometric Coefficient of Variation 50.1 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | AUC0-inf of Nintedanib in Course 1 | 349 ng*h/mL | Geometric Coefficient of Variation 25.6 |
Secondary
Clinical Relevant Abnormalities in Laboratory Parameters
Number of participants with clinically relevant abnormalities in laboratory parameters reported as adverse events
Time frame: Between the first administration of docetaxel and 28 days after last administration of docetaxel and/or nintedanib, up to 1367 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Aspartate aminotransferase increased | 2 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Blood uric acid increased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Blood alkaline phosphatase increased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Blood calcium decreased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Platelet count decreased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Blood bilirubin increased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase increased | 1 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Neutrophil count decreased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Haemoglobin decreased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | C-reactive protein increased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Prothrombin level decreased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Blood thyroid stimulating hormone increased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Tri-iodothyronine free decreased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Blood chloride decreased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine present | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Lymphocyte count decreased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Blood albumin decreased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urea increased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Electrocardiogram QT prolonged | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Alanine aminotransferase increased | 2 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | White blood cell count decreased | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Clinical Relevant Abnormalities in Laboratory Parameters | Blood potassium decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Prothrombin level decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood uric acid increased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urea increased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood alkaline phosphatase increased | 3 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood chloride decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Electrocardiogram QT prolonged | 1 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood bilirubin increased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Lymphocyte count decreased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | White blood cell count decreased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood potassium decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Aspartate aminotransferase increased | 4 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase increased | 4 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | C-reactive protein increased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Platelet count decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Neutrophil count decreased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine present | 1 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood calcium decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Alanine aminotransferase increased | 4 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood thyroid stimulating hormone increased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Haemoglobin decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood albumin decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Tri-iodothyronine free decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood thyroid stimulating hormone increased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Haemoglobin decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Lymphocyte count decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood calcium decreased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Neutrophil count decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urea increased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Tri-iodothyronine free decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine present | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood uric acid increased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Alanine aminotransferase increased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Aspartate aminotransferase increased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Electrocardiogram QT prolonged | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood alkaline phosphatase increased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase increased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood potassium decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood bilirubin increased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Platelet count decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood albumin decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | White blood cell count decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood chloride decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Prothrombin level decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | C-reactive protein increased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood alkaline phosphatase increased | 4 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Neutrophil count decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Platelet count decreased | 3 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Aspartate aminotransferase increased | 5 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | White blood cell count decreased | 3 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood calcium decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood albumin decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Alanine aminotransferase increased | 5 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood uric acid increased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase | 2 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Haemoglobin decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine present | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Electrocardiogram QT prolonged | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | C-reactive protein increased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood chloride decreased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Tri-iodothyronine free decreased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urea increased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood thyroid stimulating hormone increased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Prothrombin level decreased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase increased | 4 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Lymphocyte count decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood potassium decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood bilirubin increased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | C-reactive protein increased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Aspartate aminotransferase increased | 4 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Lymphocyte count decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood chloride decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Platelet count decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Electrocardiogram QT prolonged | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood albumin decreased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Tri-iodothyronine free decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | White blood cell count decreased | 2 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Prothrombin level decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood calcium decreased | 2 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Alanine aminotransferase increased | 4 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase increased | 4 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Neutrophil count decreased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urea increased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood potassium decreased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Haemoglobin decreased | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood alkaline phosphatase increased | 4 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood thyroid stimulating hormone increased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine present | 0 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine | 1 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood uric acid increased | 1 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood bilirubin increased | 1 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Aspartate aminotransferase increased | 3 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | White blood cell count decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Tri-iodothyronine free decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine present | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Alanine aminotransferase increased | 3 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood alkaline phosphatase increased | 3 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase increased | 3 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood bilirubin increased | 2 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Platelet count decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood calcium decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood chloride decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood thyroid stimulating hormone increased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urea increased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | C-reactive protein increased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Haemoglobin decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Lymphocyte count decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Neutrophil count decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Prothrombin level decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood albumin decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood potassium decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood uric acid increased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Electrocardiogram QT prolonged | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood potassium decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urea increased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood calcium decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Aspartate aminotransferase increased | 4 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Platelet count decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine present | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood chloride decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood albumin decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood uric acid increased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood thyroid stimulating hormone increased | 1 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Tri-iodothyronine free decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood bilirubin increased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | C-reactive protein increased | 1 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Prothrombin level decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | White blood cell count decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Electrocardiogram QT prolonged | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase increased | 4 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Lymphocyte count decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Haemoglobin decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood alkaline phosphatase increased | 2 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Neutrophil count decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Alanine aminotransferase increased | 4 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Neutrophil count decreased | 1 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood thyroid stimulating hormone increased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood chloride decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood bilirubin increased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Prothrombin level decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Tri-iodothyronine free decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase | 2 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood calcium decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Alanine aminotransferase increased | 5 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood albumin decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Gamma-glutamyltransferase increased | 4 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood alkaline phosphatase increased | 3 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood potassium decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Aspartate aminotransferase increased | 5 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine present | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urine | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Electrocardiogram QT prolonged | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood uric acid increased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | C-reactive protein increased | 1 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | White blood cell count decreased | 2 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Lymphocyte count decreased | 1 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Haemoglobin decreased | 1 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Platelet count decreased | 0 Participants |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Clinical Relevant Abnormalities in Laboratory Parameters | Blood urea increased | 0 Participants |
Secondary
Cmax of Docetaxel in Course 1
Cmax (maximum measured plasma concentration) after the first administration of docetaxel in course 1
Time frame: -0:05h before drug administration and 1h, 1.5h, 2h, 3h, 4h, 7h, 23:55h and 47:55h after drug administration
Population: Treated set (1 patient was replaced after completion of first administration of docetaxel and before any nintedanib intake. PK sampling of docetaxel for this patient was done and included in PK analysis.)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Cmax of Docetaxel in Course 1 | 3150 ng/mL | Geometric Coefficient of Variation 42.8 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Cmax of Docetaxel in Course 1 | 3550 ng/mL | Geometric Coefficient of Variation 32.2 |
Secondary
Cmax of Docetaxel in Course 2
Cmax (maximum measured plasma concentration) after the first administration of docetaxel in course 2. Docetaxel 50 mg/m2 patients were assigned to Docetaxel 60 mg/m2 in Cycle 1, but the dose was reduced to 50 mg/m2 in Cycle 2 as defined in the Clinical Trial Protocol.
Time frame: -0:05h before drug administration and 1h, 1.5h, 2h, 3h, 4h, 7h, 23:55h and 47:55h after drug administration
Population: Treated set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Cmax of Docetaxel in Course 2 | 1870 ng/mL | Geometric Coefficient of Variation 33.9 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Cmax of Docetaxel in Course 2 | 3740 ng/mL | Geometric Coefficient of Variation 33.7 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Cmax of Docetaxel in Course 2 | 4070 ng/mL | Geometric Coefficient of Variation 56.7 |
Secondary
Cmax of Nintedanib in Course 1
Cmax (maximum measured plasma concentration) after the first administration of nintedanib in course 1
Time frame: -0:05h before drug administration and 1h, 2h, 3h, 4h, 6h, 7h, 10h and 23:55h after drug administration in course 1
Population: Treated set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Cmax of Nintedanib in Course 1 | 29.3 ng/mL | Geometric Coefficient of Variation 60 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Cmax of Nintedanib in Course 1 | 33.4 ng/mL | Geometric Coefficient of Variation 91.1 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Cmax of Nintedanib in Course 1 | 59.9 ng/mL | Geometric Coefficient of Variation 43.9 |
Secondary
Disease Control
Number of participants with disease control, defined as complete response (CR) or partial response (PR) or stable disease (SD) according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.0
Time frame: Pre-treatment, every 6 weeks from treatment course 3, end of treatment (up to 1367 days)
Population: Patients who treated with nintedanib and had both baseline and at least one post-treated tumour measurement by computed tomography (CT) image
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Disease Control | Yes | 2 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Disease Control | No | 1 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Disease Control | No | 4 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Disease Control | Yes | 5 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Disease Control | No | 0 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Disease Control | Yes | 12 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Disease Control | Yes | 5 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Disease Control | No | 3 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Disease Control | No | 2 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Disease Control | Yes | 4 Participants |
Secondary
Objective Tumor Response
Number of participants with objective response defined as complete response (CR) or partial response (PR) according to the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0
Time frame: Pre-treatment, every 6 weeks from treatment course 3, end of treatment (up to 1367 days)
Population: Patients who were treated with nintedanib and had both baseline and at least one post-treatment tumour measurement by computed tomography (CT) image
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Objective Tumor Response | Yes | 0 Participants |
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Objective Tumor Response | No | 3 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Objective Tumor Response | Yes | 2 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Objective Tumor Response | No | 7 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Objective Tumor Response | Yes | 5 Participants |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Objective Tumor Response | No | 7 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Objective Tumor Response | No | 6 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Objective Tumor Response | Yes | 2 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Objective Tumor Response | Yes | 1 Participants |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Objective Tumor Response | No | 5 Participants |
Secondary
Progression-Free Survival (PFS)
For participants with known date of progression or death (of any cause): PFS \[days\] = earlier of date of progression or death - date the study treatment started + 1. For participants known to be alive without progression by the end of trial or follow-up visit: PFS (censored) \[days\] = date of last imaging when the participant is known to be progression-free and alive - date the study treatment started + 1. Progression is assessed according to RECIST version 1.0.
Time frame: Pre-treatment, every 6 weeks from treatment course 3, end of treatment (up to 1367 days)
Population: Treated set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Progression-Free Survival (PFS) | 229.5 Days |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Progression-Free Survival (PFS) | 117.0 Days |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Progression-Free Survival (PFS) | 139.0 Days |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Progression-Free Survival (PFS) | 351.0 Days |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Progression-Free Survival (PFS) | 184.0 Days |
Secondary
Time to Treatment Failure (TTF)
For participants with known date of discontinuation of the study treatment (or progression \[not necessarily confirmed by tumour imaging; can also be based on any clinical sign of tumour progression\] or death): TTF \[days\] = earlier of date of discontinuation of the study treatment, progression, or death - date the study treatment started + 1. For participants known to be alive without progression by the end of trial or follow-up visit: TTF (censored) \[days\] = date when the patient is known to be progression-free and alive - date the study treatment started + 1. Progression is assessed according to RECIST version 1.0.
Time frame: Pre-treatment, every 6 weeks from treatment course 3, end of treatment (up to 1367 days)
Population: Treated set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | Time to Treatment Failure (TTF) | 200.0 Days |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | Time to Treatment Failure (TTF) | 83.5 Days |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | Time to Treatment Failure (TTF) | 134.0 Days |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | Time to Treatment Failure (TTF) | 87.0 Days |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | Time to Treatment Failure (TTF) | 176.0 Days |