Neoplasms
Conditions
Brief summary
The primary objective of the current study is to investigate the Maximum Tolerated Dose (MTD) in terms of safety and tolerability of the combination of BI 6727 with BIBW 2992, in patients with advanced or metastatic solid tumours. Dosages of both BI 6727 and BIBW 2992 will be varied to establish the MTD of the combination. Two combination treatment schedules will be tested, the MTD of each combination will be determined. Secondary objectives are the exploration of pharmacokinetics, overall safety and preliminary efficacy.
Interventions
DRUGBI 6727 + BIBW 2992
BI 6727 administered i.v. every 21 days + BIBW 2992 given orally once a day
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with histologically or cytologically confirmed diagnosis of advanced, non resectable and/or metastatic, relapsed or refractory solid tumours not amenable to standard therapy and for whom no therapy of proven efficacy exists * Eastern Cooperative Oncology Group performance score 0 - 2 * Recovery from clinically significant toxicities from previous systemic anti-cancer therapies or radiotherapy
Exclusion criteria
* Serious illness, concomitant non-oncological disease or mental problem considered by the investigator to be incompatible with participation to the trial * Known hypersensitivity to the trial drugs or their excipients * Treatment with any other investigational drug or active participation in any other interventional trial within 28 days before first administration of trial drug(s) or concomitantly with this trial * Major surgery or radiotherapy within 28 days before start of therapy or concomitantly with this trial * Systemic anti-cancer therapy within 28 days before start of therapy or concomitantly with this trial * Requirements for treatment with any of the prohibited concomitant medications * Active infectious disease or known HIV I/II infection * Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhoea * Active brain metastases * History or presence of cardiovascular abnormalities deemed clinically relevant by the investigator * Cardial left ventricular function with resting ejection fraction \< 50% * Inadequate hepatic, renal and haematologic organ function * QT prolongation deemed clinically relevant by the investigator * Active alcohol or drug abuse * Women of childbearing potential and men who are able to father a child unwilling to use a medically acceptable method of contraception during the trial and 28 days thereafter * Pregnancy or breast-feeding * Patients unable to comply with the protocol * Patients with known pre-existing interstitial lung disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLT) | 22 Days | MTD was defined on the basis of DLTs occuring during Cycle 1 of the dose escalation part in each of the 2 treatment schedules. DLTs were defined as drug related based on Common Terminology Criteria for AE's (CTCAE) Grade(G) :1) G4 neutropenia (ANC, including bands, \<500/mm³) for more than 7 days, 2) G3 or 4 neutropenia associated with fever \>38.5° C (febrile neutropenia),3) Neutropenic infection G ≥3, 4) G4 thrombocytopenia or G3 thrombocytopenia associated with bleeding requiring whole blood transfusion.5) Non-haematological G ≥3 toxicity excluding: (a) untreated G3 diarrhoea, (b) untreated G3 nausea and/or vomiting, (c) untreated G3 rash. 6) G2 increase in AST and/or ALT in conjunction with an elevated bilirubin level of G ≥2, 7) G2 nausea and/or vomiting despite optimal supportive/antiemetic treatment for at least 7consecutive days. 8) G2 diarrhoea for 2 or more consecutive days despite antidiarrhoeal medication/hydration, 9) Decrease in left ventricular function G ≥2. |
| Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib. | MTD was assessed during the first cycle of combination of Volasertib and Afatinib therapy (22 days) | Maximum Tolerable Dose (MTD) was determined by dose escalation for volasertib and afatinib. The 3 + 3 design with de-escalation for both the Schedules A and B. Patients were sequentially allocated to the dose cohorts. Apart from allocation to the treatment schedules, escalation and/or de-escalation to determine the MTD occurred independently within the 2 dose schedules. Cohorts of 3 patients were to be treated at the starting dose levels according to the treatment schedule. Before entering patients at a higher dose level, all patients at the previous dose level combination had to complete at least the initial cycle of 21 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0 | After the first drug administration until 28 days after the last drug administration, up to 413 days. | Number of patients with investigator defined drug-related adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) criteria v 3.0 |
| Number of Patients With Objective Response (OR) | Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment). | Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.1. OR is defined as complete response (CR) or partial response (PR). As Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions. |
| Number of Patients With Best Overall Response. | Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment). | Best overall response based on response evaluation criteria in solid tumors (RECIST) version 1.1. Best overall response is defined as complete response, partial response, stable disease, progressive disease or not evaluable. As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. |
| Number of Patients With Disease Control | Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment). | Disease control based on response evaluation criteria in solid tumors (RECIST) version 1.1. Patients who had a best overall tumour response of complete response (CR), partial response (PR) or stable disease (SD) were assessed to show disease control. As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. |
Countries
Belgium
Participant flow
Recruitment details
Aspartate amino transferase (AST) ; Alanine amino transferase (ALT) and Eastern Cooperative Oncology Group (ECOG).
Pre-assignment details
This is a Phase 1, open label, non randomised and dose escalation trial. There was no control group. The Combination of Volasertib and Afatinib to be investigated in two treatment schedules (A & B). In Schedule B the starting doses will be depend on the outcome of the MTD determination from treatment schedule A.
Participants by arm
| Arm | Count |
|---|---|
| Volasertib150 mg+Afatinib 30 mg (Schedule A) Schedule A : Volasertib (Vol) 150 mg on Day 1 and afatinib (aftb) 30 mg from Day 2 to Day 21.
Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion. | 3 |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) Schedule A : Volasertib 225 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21.
Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion. | 3 |
| Volasertib 300 mg+Afatinib 30 mg (Schedule A) Schedule A : Volasertib 300 mg on Day 1 and afatinib 30 mg from Day 2 to Day 21.
Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion. | 20 |
| Volasertib 300 mg+Afatinib 40 mg (Schedule A) Schedule A : Volasertib 300 mg on Day 1 and afatinib 40 mg from Day 2 to Day 21.
Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion. | 3 |
| Volasertib 300 mg+Afatinib 50 mg (Schedule B) Schedule B: Volasertib 300 mg on Day 1 and afatinib 50 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21).
Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion. | 3 |
| Volasertib 300 mg+Afatinib 70 mg (Schedule B) Schedule B: Volasertib 300 mg on Day 1 and afatinib 70 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21).
Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion. | 19 |
| Volasertib 300 mg+Afatinib 90 mg (Schedule B) Schedule B : Volasertib 300 mg on Day 1 and afatinib 90 mg pulsed from Day 2 to Day 6 (no administration of afatinib from Day 7 to 21).
Cycle 1 was completed after 21 days on Day 22. All subsequent cycles lasted 21 days. Patients that started a second cycle were to be co-administered with volasertib and afatinib on Day 1 of the second cycle. Afatinib was to be taken before the start of the volasertib infusion. | 6 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Other AE | 0 | 0 | 4 | 0 | 0 | 3 | 2 |
| Overall Study | other than stated above | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Progressive disease | 3 | 3 | 13 | 3 | 3 | 16 | 3 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Volasertib150 mg+Afatinib 30 mg (Schedule A) | Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Volasertib 300 mg+Afatinib 30 mg (Schedule A) | Volasertib 300 mg+Afatinib 40 mg (Schedule A) | Volasertib 300 mg+Afatinib 50 mg (Schedule B) | Volasertib 300 mg+Afatinib 70 mg (Schedule B) | Volasertib 300 mg+Afatinib 90 mg (Schedule B) |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.3 years STANDARD_DEVIATION 9.4 | 57.0 years STANDARD_DEVIATION 18.7 | 48.7 years STANDARD_DEVIATION 6.1 | 54.5 years STANDARD_DEVIATION 7.6 | 57.0 years STANDARD_DEVIATION 10.8 | 62.3 years STANDARD_DEVIATION 4.9 | 61.9 years STANDARD_DEVIATION 9.3 | 64.2 years STANDARD_DEVIATION 6 |
| ECOG at screening 0 | 20 Participants | 1 Participants | 2 Participants | 8 Participants | 1 Participants | 1 Participants | 5 Participants | 2 Participants |
| ECOG at screening 1 | 34 Participants | 2 Participants | 1 Participants | 11 Participants | 2 Participants | 2 Participants | 13 Participants | 3 Participants |
| ECOG at screening 2 | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 28 Participants | 2 Participants | 1 Participants | 10 Participants | 2 Participants | 0 Participants | 10 Participants | 3 Participants |
| Sex: Female, Male Male | 29 Participants | 1 Participants | 2 Participants | 10 Participants | 1 Participants | 3 Participants | 9 Participants | 3 Participants |
| Tumour classification Anal region | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Tumour classification Biliary tree | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Tumour classification Cancers of breast | 5 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Tumour classification Colorectal (col/rec) | 23 Participants | 1 Participants | 0 Participants | 6 Participants | 0 Participants | 2 Participants | 12 Participants | 2 Participants |
| Tumour classification Gastrointest. tract | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Tumour classification Genitourinary system | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Tumour classification Gynecologic cancers | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Tumour classification Head & neck cancers | 9 Participants | 0 Participants | 1 Participants | 6 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Tumour classification Missing | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Tumour classification Non small cell lung | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Tumour classification Other | 4 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Tumour classification Pancreas | 5 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants |
| Tumour classification Soft tissue/oss sarc | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Tumour classification Ureter | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 18 / 20 | 3 / 3 | 3 / 3 | 19 / 19 | 6 / 6 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 11 / 20 | 2 / 3 | 1 / 3 | 12 / 19 | 3 / 6 |
Outcome results
Primary
Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib.
Maximum Tolerable Dose (MTD) was determined by dose escalation for volasertib and afatinib. The 3 + 3 design with de-escalation for both the Schedules A and B. Patients were sequentially allocated to the dose cohorts. Apart from allocation to the treatment schedules, escalation and/or de-escalation to determine the MTD occurred independently within the 2 dose schedules. Cohorts of 3 patients were to be treated at the starting dose levels according to the treatment schedule. Before entering patients at a higher dose level, all patients at the previous dose level combination had to complete at least the initial cycle of 21 days.
Time frame: MTD was assessed during the first cycle of combination of Volasertib and Afatinib therapy (22 days)
Population: Treated Set (TS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib. | Volasertib | 300 mg |
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib. | Afatinib | 30 mg |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib. | Volasertib | 300 mg |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib. | Afatinib | 70 mg |
Primary
Number of Participants With Dose Limiting Toxicities (DLT)
MTD was defined on the basis of DLTs occuring during Cycle 1 of the dose escalation part in each of the 2 treatment schedules. DLTs were defined as drug related based on Common Terminology Criteria for AE's (CTCAE) Grade(G) :1) G4 neutropenia (ANC, including bands, \<500/mm³) for more than 7 days, 2) G3 or 4 neutropenia associated with fever \>38.5° C (febrile neutropenia),3) Neutropenic infection G ≥3, 4) G4 thrombocytopenia or G3 thrombocytopenia associated with bleeding requiring whole blood transfusion.5) Non-haematological G ≥3 toxicity excluding: (a) untreated G3 diarrhoea, (b) untreated G3 nausea and/or vomiting, (c) untreated G3 rash. 6) G2 increase in AST and/or ALT in conjunction with an elevated bilirubin level of G ≥2, 7) G2 nausea and/or vomiting despite optimal supportive/antiemetic treatment for at least 7consecutive days. 8) G2 diarrhoea for 2 or more consecutive days despite antidiarrhoeal medication/hydration, 9) Decrease in left ventricular function G ≥2.
Time frame: 22 Days
Population: Treated Set (TS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Number of Participants With Dose Limiting Toxicities (DLT) | 0 participants |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Number of Participants With Dose Limiting Toxicities (DLT) | 0 participants |
| Volasertib 300 mg+Afatinib 30 mg (Schedule A) | Number of Participants With Dose Limiting Toxicities (DLT) | 3 participants |
| Volasertib 300 mg+Afatinib 40 mg (Schedule A) | Number of Participants With Dose Limiting Toxicities (DLT) | 2 participants |
| Volasertib 300 mg+Afatinib 50 mg (Schedule B) | Number of Participants With Dose Limiting Toxicities (DLT) | 0 participants |
| Volasertib 300 mg+Afatinib 70 mg (Schedule B) | Number of Participants With Dose Limiting Toxicities (DLT) | 5 participants |
| Volasertib 300 mg+Afatinib 90 mg (Schedule B) | Number of Participants With Dose Limiting Toxicities (DLT) | 2 participants |
Secondary
Number of Patients With Best Overall Response.
Best overall response based on response evaluation criteria in solid tumors (RECIST) version 1.1. Best overall response is defined as complete response, partial response, stable disease, progressive disease or not evaluable. As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Time frame: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).
Population: Treated Set (TS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Not evaluable | 0 participants |
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Unknown | 0 participants |
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Partial response | 1 participants |
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Stable disease | 0 participants |
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Progressive disease | 2 participants |
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Complete response | 0 participants |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Complete response | 0 participants |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Not evaluable | 0 participants |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Stable disease | 0 participants |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Progressive disease | 3 participants |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Unknown | 0 participants |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Partial response | 0 participants |
| Volasertib 300 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Stable disease | 8 participants |
| Volasertib 300 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Progressive disease | 8 participants |
| Volasertib 300 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Unknown | 2 participants |
| Volasertib 300 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Partial response | 1 participants |
| Volasertib 300 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Not evaluable | 1 participants |
| Volasertib 300 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Best Overall Response. | Complete response | 0 participants |
| Volasertib 300 mg+Afatinib 40 mg (Schedule A) | Number of Patients With Best Overall Response. | Not evaluable | 0 participants |
| Volasertib 300 mg+Afatinib 40 mg (Schedule A) | Number of Patients With Best Overall Response. | Complete response | 0 participants |
| Volasertib 300 mg+Afatinib 40 mg (Schedule A) | Number of Patients With Best Overall Response. | Partial response | 0 participants |
| Volasertib 300 mg+Afatinib 40 mg (Schedule A) | Number of Patients With Best Overall Response. | Stable disease | 0 participants |
| Volasertib 300 mg+Afatinib 40 mg (Schedule A) | Number of Patients With Best Overall Response. | Progressive disease | 3 participants |
| Volasertib 300 mg+Afatinib 40 mg (Schedule A) | Number of Patients With Best Overall Response. | Unknown | 0 participants |
| Volasertib 300 mg+Afatinib 50 mg (Schedule B) | Number of Patients With Best Overall Response. | Partial response | 0 participants |
| Volasertib 300 mg+Afatinib 50 mg (Schedule B) | Number of Patients With Best Overall Response. | Complete response | 0 participants |
| Volasertib 300 mg+Afatinib 50 mg (Schedule B) | Number of Patients With Best Overall Response. | Not evaluable | 0 participants |
| Volasertib 300 mg+Afatinib 50 mg (Schedule B) | Number of Patients With Best Overall Response. | Stable disease | 1 participants |
| Volasertib 300 mg+Afatinib 50 mg (Schedule B) | Number of Patients With Best Overall Response. | Unknown | 0 participants |
| Volasertib 300 mg+Afatinib 50 mg (Schedule B) | Number of Patients With Best Overall Response. | Progressive disease | 2 participants |
| Volasertib 300 mg+Afatinib 70 mg (Schedule B) | Number of Patients With Best Overall Response. | Not evaluable | 0 participants |
| Volasertib 300 mg+Afatinib 70 mg (Schedule B) | Number of Patients With Best Overall Response. | Progressive disease | 10 participants |
| Volasertib 300 mg+Afatinib 70 mg (Schedule B) | Number of Patients With Best Overall Response. | Partial response | 0 participants |
| Volasertib 300 mg+Afatinib 70 mg (Schedule B) | Number of Patients With Best Overall Response. | Unknown | 4 participants |
| Volasertib 300 mg+Afatinib 70 mg (Schedule B) | Number of Patients With Best Overall Response. | Complete response | 0 participants |
| Volasertib 300 mg+Afatinib 70 mg (Schedule B) | Number of Patients With Best Overall Response. | Stable disease | 5 participants |
| Volasertib 300 mg+Afatinib 90 mg (Schedule B) | Number of Patients With Best Overall Response. | Progressive disease | 4 participants |
| Volasertib 300 mg+Afatinib 90 mg (Schedule B) | Number of Patients With Best Overall Response. | Stable disease | 2 participants |
| Volasertib 300 mg+Afatinib 90 mg (Schedule B) | Number of Patients With Best Overall Response. | Unknown | 0 participants |
| Volasertib 300 mg+Afatinib 90 mg (Schedule B) | Number of Patients With Best Overall Response. | Partial response | 0 participants |
| Volasertib 300 mg+Afatinib 90 mg (Schedule B) | Number of Patients With Best Overall Response. | Not evaluable | 0 participants |
| Volasertib 300 mg+Afatinib 90 mg (Schedule B) | Number of Patients With Best Overall Response. | Complete response | 0 participants |
Secondary
Number of Patients With Disease Control
Disease control based on response evaluation criteria in solid tumors (RECIST) version 1.1. Patients who had a best overall tumour response of complete response (CR), partial response (PR) or stable disease (SD) were assessed to show disease control. As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Time frame: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).
Population: Treated Set (TS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Disease Control | NO | 2 participants |
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Disease Control | YES | 1 participants |
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Disease Control | Unknown | 0 participants |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Disease Control | YES | 0 participants |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Disease Control | Unknown | 0 participants |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Disease Control | NO | 3 participants |
| Volasertib 300 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Disease Control | YES | 9 participants |
| Volasertib 300 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Disease Control | Unknown | 2 participants |
| Volasertib 300 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Disease Control | NO | 9 participants |
| Volasertib 300 mg+Afatinib 40 mg (Schedule A) | Number of Patients With Disease Control | Unknown | 0 participants |
| Volasertib 300 mg+Afatinib 40 mg (Schedule A) | Number of Patients With Disease Control | YES | 0 participants |
| Volasertib 300 mg+Afatinib 40 mg (Schedule A) | Number of Patients With Disease Control | NO | 3 participants |
| Volasertib 300 mg+Afatinib 50 mg (Schedule B) | Number of Patients With Disease Control | Unknown | 0 participants |
| Volasertib 300 mg+Afatinib 50 mg (Schedule B) | Number of Patients With Disease Control | NO | 2 participants |
| Volasertib 300 mg+Afatinib 50 mg (Schedule B) | Number of Patients With Disease Control | YES | 1 participants |
| Volasertib 300 mg+Afatinib 70 mg (Schedule B) | Number of Patients With Disease Control | NO | 10 participants |
| Volasertib 300 mg+Afatinib 70 mg (Schedule B) | Number of Patients With Disease Control | Unknown | 4 participants |
| Volasertib 300 mg+Afatinib 70 mg (Schedule B) | Number of Patients With Disease Control | YES | 5 participants |
| Volasertib 300 mg+Afatinib 90 mg (Schedule B) | Number of Patients With Disease Control | Unknown | 0 participants |
| Volasertib 300 mg+Afatinib 90 mg (Schedule B) | Number of Patients With Disease Control | YES | 2 participants |
| Volasertib 300 mg+Afatinib 90 mg (Schedule B) | Number of Patients With Disease Control | NO | 4 participants |
Secondary
Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0
Number of patients with investigator defined drug-related adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) criteria v 3.0
Time frame: After the first drug administration until 28 days after the last drug administration, up to 413 days.
Population: Treated Set (TS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0 | 3 participants |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0 | 3 participants |
| Volasertib 300 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0 | 18 participants |
| Volasertib 300 mg+Afatinib 40 mg (Schedule A) | Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0 | 3 participants |
| Volasertib 300 mg+Afatinib 50 mg (Schedule B) | Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0 | 3 participants |
| Volasertib 300 mg+Afatinib 70 mg (Schedule B) | Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0 | 19 participants |
| Volasertib 300 mg+Afatinib 90 mg (Schedule B) | Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0 | 6 participants |
Secondary
Number of Patients With Objective Response (OR)
Objective tumor response based on response evaluation criteria in solid tumors (RECIST) version 1.1. OR is defined as complete response (CR) or partial response (PR). As Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by using appropriate radiology techniques: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.
Time frame: Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).
Population: Treated Set (TS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Objective Response (OR) | Yes | 1 participants |
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Objective Response (OR) | Unknown | 0 participants |
| Volasertib150 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Objective Response (OR) | No | 2 participants |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Objective Response (OR) | No | 3 participants |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Objective Response (OR) | Unknown | 0 participants |
| Volasertib 225 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Objective Response (OR) | Yes | 0 participants |
| Volasertib 300 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Objective Response (OR) | Yes | 1 participants |
| Volasertib 300 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Objective Response (OR) | No | 17 participants |
| Volasertib 300 mg+Afatinib 30 mg (Schedule A) | Number of Patients With Objective Response (OR) | Unknown | 2 participants |
| Volasertib 300 mg+Afatinib 40 mg (Schedule A) | Number of Patients With Objective Response (OR) | No | 3 participants |
| Volasertib 300 mg+Afatinib 40 mg (Schedule A) | Number of Patients With Objective Response (OR) | Yes | 0 participants |
| Volasertib 300 mg+Afatinib 40 mg (Schedule A) | Number of Patients With Objective Response (OR) | Unknown | 0 participants |
| Volasertib 300 mg+Afatinib 50 mg (Schedule B) | Number of Patients With Objective Response (OR) | No | 3 participants |
| Volasertib 300 mg+Afatinib 50 mg (Schedule B) | Number of Patients With Objective Response (OR) | Yes | 0 participants |
| Volasertib 300 mg+Afatinib 50 mg (Schedule B) | Number of Patients With Objective Response (OR) | Unknown | 0 participants |
| Volasertib 300 mg+Afatinib 70 mg (Schedule B) | Number of Patients With Objective Response (OR) | Yes | 0 participants |
| Volasertib 300 mg+Afatinib 70 mg (Schedule B) | Number of Patients With Objective Response (OR) | Unknown | 4 participants |
| Volasertib 300 mg+Afatinib 70 mg (Schedule B) | Number of Patients With Objective Response (OR) | No | 15 participants |
| Volasertib 300 mg+Afatinib 90 mg (Schedule B) | Number of Patients With Objective Response (OR) | Unknown | 0 participants |
| Volasertib 300 mg+Afatinib 90 mg (Schedule B) | Number of Patients With Objective Response (OR) | No | 6 participants |
| Volasertib 300 mg+Afatinib 90 mg (Schedule B) | Number of Patients With Objective Response (OR) | Yes | 0 participants |