Neoplasms
Conditions
Brief summary
The aim of the Phase Ia (dose escalation) part of this trial is to assess the maximum tolerated dose (MTD) of BI 847325 administered at escalating doses in 2 treatment arms. In the Phase Ib expansion part of the trial, the aim is to further evaluate the safety profile of BI 847325 at the recommended dose and schedule and to assess target modulation and the potential antitumour efficacy in patients with selected tumour types.
Interventions
DRUGday 1 to day 5
low to high dose
DRUGday 1 to day 14
low to high dose
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with a histologically or cytologically confirmed diagnosis of an advanced unresectable and/or metastatic solid tumour, and who have failed conventional treatment or for whom no therapy of proven efficacy exists or who are not amenable to standard therapies. 2. Age 18 years and older 3. Written informed consent consistent with International conference on harmonization - Good clinical practice (ICH-GCP) and local legislation 4. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1. 5. Recovery of therapy-related toxicities from previous anti-tumour therapies to Common Terminology Criteria for Adverse Events (CTCAE) = grade 1 (with the exception of alopecia). 6. Written informed consent to the use of archival tumour sample for determination of the BRAF/Tat sarcoma viral oncogene homolog (RAS) mutational status. 7. Life expectancy of at least 12 weeks. 8. In escalation phase, when pharmacokinetic (PK) close to predicted Cmax or when signs of progressive disease (PD) modulation present, optional tumour biopsies (at same timepoints as in expansion phase) for the patients who consented to it. In addition, all patients included in the expansion phase (part Ib) must: 9. have been diagnosed with one of the following tumours: melanoma, colorectal carcinoma, Non Small Cell Lung Cancer (NSCLC) or exocrine pancreas adenocarcinoma, and have been shown on their archival tumour sample to have KRAS or BRAF mutation. 10. have a measurable disease. 11. have documented/proven progressive disease within the last 6 months, according to Response Evaluation Criteria In Solid Tumours (RECIST) criteria 11\. have a tumour lesion accessible for biopsies (pre- and post-treatment): this is mandatory for patients with colorectal carcinoma or melanoma, optional for patients with NSCLC or exocrine pancreas adenocarcinoma.
Exclusion criteria
1. Inability to swallow tablets. 2. Additional other serious illness , concomitant non-oncological disease (e.g. active infectious disease or known chronic Hepatitis B/Hepatitis C infection and HIV), or ongoing toxicity from prior therapies considered by the investigator to potentially compromise patient's safety in this trial. 3. Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the last 28 days. 4. Second malignancy currently requiring another anti-cancer therapy. 5. Absolute neutrophil count less than 1500/mm3. 6. Platelet count less than 100 000/mm3. 7. Bilirubin greater than 1.5 mg/dL (\>26 µmol/L, Système international (SI) unit equivalent) (except known Gilbert's syndrome). 8. Aspartate amino transferase (AST) and/or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (if related to liver metastases, greater than five times the upper limit of normal). 9. Serum creatinine greater than 1.5 mg/dL (\>132 µmol/L, SI unit equivalent). 10. Previous episode of QT prolongation due to a medication which, as a result of it, had to be discontinued; or long QT syndrome; or corrected QT interval (QTc) with Fridericia's correction \>480 msec on screening ECG. 11. Pregnancy or breastfeeding. 12. Women or men who are sexually active and unwilling to use a medically acceptable method of contraception. 13. Treatment with other investigational drugs or participation in another clinical interventional trial within the past four weeks before start of therapy or concomitant with this trial. 14. Systemic anti-cancer therapy or radiotherapy within the past four weeks before start of therapy or concomitantly with this trial. This restriction does not apply to Luteinizing hormone-releasing hormone (LHRH) agonists, steroids and bisphosphonates. 15. Patients unable to comply with the protocol. 16. Active alcohol or drug abuse. 17. history or presence of cardiovascular abnormalities deemed clinically relevant by the investigator. Myocardial infarction within 6 months prior to study. 18. Cardiac left ventricular ejection fraction \<50% or less than institutional lower limit of normal by Multiple Gated Acquisition scan (MUGA) or echocardiography
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 3 weeks | Occurrence of dose limiting toxicity (DLT) during the first treatment cycle for the treatment Schedules A and B. Some patients excluded from Treated Set (TS) as they were not evaluable for determination of maximum tolerated dose. Thus the number of evaluable TS patients are not the same as the number of original TS patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response | From the start of treatment until the last evaluable assessment. The data cut-off date is 29-Nov-2013 | Best overall response was the best response a patient experienced during their time on study from the start of treatment until: disease progression, the last evaluable assessment in the absence of progression, or the start of subsequent anti-cancer therapy. Death was not considered as progressive disease when determining best overall response; patients who died prior to an evaluable imaging assessment were reported as not evaluable. Some patients were excluded from TS as they were not evaluable for determination of maximum tolerated dose. Thus the number of evaluable TS patients are not the same as the number of original TS patients. |
| Objective Response | From the start of treatment and the earliest of disease progression, death, or the end of treatment. The data cut-off date is 29-Nov-2013. | Objective response was a best overall response of complete or partial response, recorded between the start of treatment and the earliest of disease progression, death, or the end of treatment. Some patients excluded from TS as they were not evaluable for determination of maximum tolerated dose. Thus the number of evaluable TS patients are not the same as the number of original TS patients. |
| Disease Control | From the start of treatment to the earliest of disease progression, death, or the end of treatment. The data cut-off date is 29-Nov-2013. | Disease control was a best overall response of complete response, partial response or stable disease, recorded between the start of treatment and the earliest of disease progression, death, or the end of treatment. Some patients excluded from TS as they were not evaluable for determination of maximum tolerated dose. Thus the number of evaluable TS patients are not the same as the number of original TS patients. |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Schedule A BI 847325 6 mg (A1) Schedule A BI 847325 6 mg/day group. Schedule A: 2 weeks on treatment, 1 week off treatment, repeated every 3 weeks. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 3 |
| Schedule A BI 847325 9 mg (A2) Schedule A BI 847325 9 mg/day group. Schedule A: 2 weeks on treatment, 1 week off treatment, repeated every 3 weeks. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 3 |
| Schedule A BI 847325 13 mg (A3) Schedule A BI 847325 13 mg/day group. Schedule A: 2 weeks on treatment, 1 week off treatment, repeated every 3 weeks. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 3 |
| Schedule A BI 847325 19 mg (A4) Schedule A BI 847325 19 mg/day group. Schedule A: 2 weeks on treatment, 1 week off treatment, repeated every 3 weeks. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 3 |
| Schedule A BI 847325 26 mg (A5) Schedule A BI 847325 26 mg/day group. Schedule A: 2 weeks on treatment, 1 week off treatment, repeated every 3 weeks. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 7 |
| Schedule A BI 847325 33 mg (A6) Schedule A BI 847325 33 mg/day group. Schedule A: 2 weeks on treatment, 1 week off treatment, repeated every 3 weeks. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 7 |
| Schedule A BI 847325 46 mg (A7) Schedule A BI 847325 46 mg/day group. Schedule A: 2 weeks on treatment, 1 week off treatment, repeated every 3 weeks. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 3 |
| Schedule A BI 847325 63 mg (A8) Schedule A BI 847325 63 mg/day group. Schedule A: 2 weeks on treatment, 1 week off treatment, repeated every 3 weeks. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 3 |
| Schedule A BI 847325 86 mg (A9) Schedule A BI 847325 86 mg/day group. Schedule A: 2 weeks on treatment, 1 week off treatment, repeated every 3 weeks. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 5 |
| Schedule A BI 847325 120 mg (A10) Schedule A BI 847325 120 mg/day group. Schedule A: 2 weeks on treatment, 1 week off treatment, repeated every 3 weeks. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 6 |
| Schedule A BI 847325 160 mg (A11) Schedule A BI 847325 160 mg/day group. Schedule A: 2 weeks on treatment, 1 week off treatment, repeated every 3 weeks. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 4 |
| Schedule B BI 847325 6 mg (B1) Schedule B BI 847325 6 mg/day group. Schedule B: 5 days on treatment, 2 days off treatment, repeated every week, in 3-week cycles. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 1 |
| Schedule B BI 847325 12 mg (B2) Schedule B BI 847325 12 mg/day group. Schedule B: 5 days on treatment, 2 days off treatment, repeated every week, in 3-week cycles. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 1 |
| Schedule B BI 847325 23 mg (B3) Schedule B BI 847325 23 mg/day group. Schedule B: 5 days on treatment, 2 days off treatment, repeated every week, in 3-week cycles. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 1 |
| Schedule B BI 847325 46 mg (B4) Schedule B BI 847325 46 mg/day group. Schedule B: 5 days on treatment, 2 days off treatment, repeated every week, in 3-week cycles. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 1 |
| Schedule B BI 847325 90 mg (B5) Schedule B BI 847325 90 mg/day group. Schedule B: 5 days on treatment, 2 days off treatment, repeated every week, in 3-week cycles. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 3 |
| Schedule B BI 847325 180 mg (B6) Schedule B BI 847325 180 mg/day group. Schedule B: 5 days on treatment, 2 days off treatment, repeated every week, in 3-week cycles. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 3 |
| Schedule B BI 847325 130 mg (B7) Schedule B BI 847325 130 mg/day group. Schedule B: 5 days on treatment, 2 days off treatment, repeated every week, in 3-week cycles. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 6 |
| Schedule B BI 847325 150 mg (B8) Schedule B BI 847325 150 mg/day group. Schedule B: 5 days on treatment, 2 days off treatment, repeated every week, in 3-week cycles. BI 847325 tablet(s) administered once daily in the morning 1 hour before breakfast and taken with at least 250 mL of water. | 6 |
| Total | 69 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event, non-fatal | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Adverse Event, serious fatal | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Dose limiting toxicity | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 |
| Overall Study | Progressive Disease | 3 | 2 | 3 | 3 | 6 | 6 | 3 | 3 | 3 | 6 | 2 | 1 | 1 | 1 | 1 | 3 | 2 | 3 | 4 |
| Overall Study | Reason not mentioned above | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Schedule A BI 847325 6 mg (A1) | Schedule A BI 847325 9 mg (A2) | Schedule A BI 847325 13 mg (A3) | Schedule A BI 847325 19 mg (A4) | Schedule A BI 847325 26 mg (A5) | Schedule A BI 847325 33 mg (A6) | Schedule A BI 847325 46 mg (A7) | Schedule A BI 847325 63 mg (A8) | Schedule A BI 847325 86 mg (A9) | Schedule A BI 847325 120 mg (A10) | Schedule A BI 847325 160 mg (A11) | Schedule B BI 847325 6 mg (B1) | Schedule B BI 847325 12 mg (B2) | Schedule B BI 847325 23 mg (B3) | Schedule B BI 847325 46 mg (B4) | Schedule B BI 847325 90 mg (B5) | Schedule B BI 847325 180 mg (B6) | Schedule B BI 847325 130 mg (B7) | Schedule B BI 847325 150 mg (B8) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.7 Years STANDARD_DEVIATION 8.1 | 62.7 Years STANDARD_DEVIATION 3.5 | 58.7 Years STANDARD_DEVIATION 4.2 | 57.7 Years STANDARD_DEVIATION 12.2 | 58.9 Years STANDARD_DEVIATION 9.8 | 55.3 Years STANDARD_DEVIATION 14.1 | 66 Years STANDARD_DEVIATION 10.4 | 55.3 Years STANDARD_DEVIATION 5.1 | 58.6 Years STANDARD_DEVIATION 9.9 | 59.3 Years STANDARD_DEVIATION 8.2 | 55 Years STANDARD_DEVIATION 7.4 | 60 Years STANDARD_DEVIATION 0 | 49 Years STANDARD_DEVIATION 0 | 44 Years STANDARD_DEVIATION 0 | 62 Years STANDARD_DEVIATION 0 | 49.3 Years STANDARD_DEVIATION 15.3 | 42.7 Years STANDARD_DEVIATION 3.5 | 62.2 Years STANDARD_DEVIATION 13.5 | 51.7 Years STANDARD_DEVIATION 13.4 | 56.8 Years STANDARD_DEVIATION 10.6 |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants | 1 Participants | 5 Participants | 3 Participants | 2 Participants | 0 Participants | 3 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants | 4 Participants | 36 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 1 Participants | 3 Participants | 2 Participants | 5 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 33 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 | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 2 / 3 | 7 / 7 | 7 / 7 | 3 / 3 | 3 / 3 | 5 / 5 | 6 / 6 | 4 / 4 | 46 / 47 | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 3 / 3 | 3 / 3 | 6 / 6 | 6 / 6 | 22 / 22 | 68 / 69 |
| serious Total, serious adverse events | 1 / 3 | 1 / 3 | 0 / 3 | 1 / 3 | 5 / 7 | 3 / 7 | 1 / 3 | 0 / 3 | 4 / 5 | 2 / 6 | 4 / 4 | 22 / 47 | 1 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 1 / 3 | 2 / 3 | 4 / 6 | 1 / 6 | 9 / 22 | 31 / 69 |
Outcome results
Primary
Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study
Occurrence of dose limiting toxicity (DLT) during the first treatment cycle for the treatment Schedules A and B. Some patients excluded from Treated Set (TS) as they were not evaluable for determination of maximum tolerated dose. Thus the number of evaluable TS patients are not the same as the number of original TS patients.
Time frame: 3 weeks
Population: Treated Set (TS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Schedule A BI 847325 6 mg (A1) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 0 Percentage of participants |
| Schedule A BI 847325 9 mg (A2) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 0 Percentage of participants |
| Schedule A BI 847325 13 mg (A3) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 0 Percentage of participants |
| Schedule A BI 847325 19 mg (A4) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 0 Percentage of participants |
| Schedule A BI 847325 26 mg (A5) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 16.7 Percentage of participants |
| Schedule A BI 847325 33 mg (A6) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 16.7 Percentage of participants |
| Schedule A BI 847325 46 mg (A7) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 0 Percentage of participants |
| Schedule A BI 847325 63 mg (A8) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 0 Percentage of participants |
| Schedule A BI 847325 86 mg (A9) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 0 Percentage of participants |
| Schedule A BI 847325 120 mg (A10) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 16.7 Percentage of participants |
| Schedule A BI 847325 160 mg (A11) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 66.7 Percentage of participants |
| Schedule B BI 847325 6 mg (B1) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 0 Percentage of participants |
| Schedule B BI 847325 12 mg (B2) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 0 Percentage of participants |
| Schedule B BI 847325 23 mg (B3) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 0 Percentage of participants |
| Schedule B BI 847325 46 mg (B4) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 0 Percentage of participants |
| Schedule B BI 847325 90 mg (B5) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 0 Percentage of participants |
| Schedule B BI 847325 180 mg (B6) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 66.7 Percentage of participants |
| Schedule B BI 847325 130 mg (B7) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 16.7 Percentage of participants |
| Schedule B BI 847325 150 mg (B8) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 16.7 Percentage of participants |
| Schedule A Total (Total A) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 11.9 Percentage of participants |
| Schedule B Total (Total B) | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 18.2 Percentage of participants |
| Total Patients | Percentage of Patients With Dose Limiting Toxicity During the First Treatment Cycle in Phase Ia Part of the Study | 14.1 Percentage of participants |
Secondary
Best Overall Response
Best overall response was the best response a patient experienced during their time on study from the start of treatment until: disease progression, the last evaluable assessment in the absence of progression, or the start of subsequent anti-cancer therapy. Death was not considered as progressive disease when determining best overall response; patients who died prior to an evaluable imaging assessment were reported as not evaluable. Some patients were excluded from TS as they were not evaluable for determination of maximum tolerated dose. Thus the number of evaluable TS patients are not the same as the number of original TS patients.
Time frame: From the start of treatment until the last evaluable assessment. The data cut-off date is 29-Nov-2013
Population: TS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Schedule A BI 847325 6 mg (A1) | Best Overall Response | stable disease | 0 Participants |
| Schedule A BI 847325 6 mg (A1) | Best Overall Response | not evaluable | 0 Participants |
| Schedule A BI 847325 6 mg (A1) | Best Overall Response | progressive disease | 3 Participants |
| Schedule A BI 847325 6 mg (A1) | Best Overall Response | complete response | 0 Participants |
| Schedule A BI 847325 6 mg (A1) | Best Overall Response | partial response | 0 Participants |
| Schedule A BI 847325 9 mg (A2) | Best Overall Response | stable disease | 0 Participants |
| Schedule A BI 847325 9 mg (A2) | Best Overall Response | complete response | 0 Participants |
| Schedule A BI 847325 9 mg (A2) | Best Overall Response | partial response | 0 Participants |
| Schedule A BI 847325 9 mg (A2) | Best Overall Response | not evaluable | 1 Participants |
| Schedule A BI 847325 9 mg (A2) | Best Overall Response | progressive disease | 2 Participants |
| Schedule A BI 847325 13 mg (A3) | Best Overall Response | not evaluable | 0 Participants |
| Schedule A BI 847325 13 mg (A3) | Best Overall Response | stable disease | 1 Participants |
| Schedule A BI 847325 13 mg (A3) | Best Overall Response | progressive disease | 2 Participants |
| Schedule A BI 847325 13 mg (A3) | Best Overall Response | complete response | 0 Participants |
| Schedule A BI 847325 13 mg (A3) | Best Overall Response | partial response | 0 Participants |
| Schedule A BI 847325 19 mg (A4) | Best Overall Response | partial response | 0 Participants |
| Schedule A BI 847325 19 mg (A4) | Best Overall Response | not evaluable | 0 Participants |
| Schedule A BI 847325 19 mg (A4) | Best Overall Response | stable disease | 1 Participants |
| Schedule A BI 847325 19 mg (A4) | Best Overall Response | progressive disease | 2 Participants |
| Schedule A BI 847325 19 mg (A4) | Best Overall Response | complete response | 0 Participants |
| Schedule A BI 847325 26 mg (A5) | Best Overall Response | stable disease | 3 Participants |
| Schedule A BI 847325 26 mg (A5) | Best Overall Response | complete response | 0 Participants |
| Schedule A BI 847325 26 mg (A5) | Best Overall Response | not evaluable | 2 Participants |
| Schedule A BI 847325 26 mg (A5) | Best Overall Response | partial response | 0 Participants |
| Schedule A BI 847325 26 mg (A5) | Best Overall Response | progressive disease | 2 Participants |
| Schedule A BI 847325 33 mg (A6) | Best Overall Response | complete response | 0 Participants |
| Schedule A BI 847325 33 mg (A6) | Best Overall Response | progressive disease | 4 Participants |
| Schedule A BI 847325 33 mg (A6) | Best Overall Response | partial response | 0 Participants |
| Schedule A BI 847325 33 mg (A6) | Best Overall Response | not evaluable | 2 Participants |
| Schedule A BI 847325 33 mg (A6) | Best Overall Response | stable disease | 1 Participants |
| Schedule A BI 847325 46 mg (A7) | Best Overall Response | not evaluable | 0 Participants |
| Schedule A BI 847325 46 mg (A7) | Best Overall Response | partial response | 0 Participants |
| Schedule A BI 847325 46 mg (A7) | Best Overall Response | progressive disease | 3 Participants |
| Schedule A BI 847325 46 mg (A7) | Best Overall Response | complete response | 0 Participants |
| Schedule A BI 847325 46 mg (A7) | Best Overall Response | stable disease | 0 Participants |
| Schedule A BI 847325 63 mg (A8) | Best Overall Response | complete response | 0 Participants |
| Schedule A BI 847325 63 mg (A8) | Best Overall Response | partial response | 0 Participants |
| Schedule A BI 847325 63 mg (A8) | Best Overall Response | stable disease | 1 Participants |
| Schedule A BI 847325 63 mg (A8) | Best Overall Response | not evaluable | 1 Participants |
| Schedule A BI 847325 63 mg (A8) | Best Overall Response | progressive disease | 1 Participants |
| Schedule A BI 847325 86 mg (A9) | Best Overall Response | progressive disease | 2 Participants |
| Schedule A BI 847325 86 mg (A9) | Best Overall Response | stable disease | 1 Participants |
| Schedule A BI 847325 86 mg (A9) | Best Overall Response | partial response | 0 Participants |
| Schedule A BI 847325 86 mg (A9) | Best Overall Response | complete response | 0 Participants |
| Schedule A BI 847325 86 mg (A9) | Best Overall Response | not evaluable | 2 Participants |
| Schedule A BI 847325 120 mg (A10) | Best Overall Response | not evaluable | 1 Participants |
| Schedule A BI 847325 120 mg (A10) | Best Overall Response | progressive disease | 3 Participants |
| Schedule A BI 847325 120 mg (A10) | Best Overall Response | partial response | 0 Participants |
| Schedule A BI 847325 120 mg (A10) | Best Overall Response | complete response | 0 Participants |
| Schedule A BI 847325 120 mg (A10) | Best Overall Response | stable disease | 2 Participants |
| Schedule A BI 847325 160 mg (A11) | Best Overall Response | complete response | 0 Participants |
| Schedule A BI 847325 160 mg (A11) | Best Overall Response | not evaluable | 2 Participants |
| Schedule A BI 847325 160 mg (A11) | Best Overall Response | partial response | 1 Participants |
| Schedule A BI 847325 160 mg (A11) | Best Overall Response | stable disease | 1 Participants |
| Schedule A BI 847325 160 mg (A11) | Best Overall Response | progressive disease | 0 Participants |
| Schedule B BI 847325 6 mg (B1) | Best Overall Response | stable disease | 0 Participants |
| Schedule B BI 847325 6 mg (B1) | Best Overall Response | complete response | 0 Participants |
| Schedule B BI 847325 6 mg (B1) | Best Overall Response | partial response | 0 Participants |
| Schedule B BI 847325 6 mg (B1) | Best Overall Response | progressive disease | 1 Participants |
| Schedule B BI 847325 6 mg (B1) | Best Overall Response | not evaluable | 0 Participants |
| Schedule B BI 847325 12 mg (B2) | Best Overall Response | progressive disease | 1 Participants |
| Schedule B BI 847325 12 mg (B2) | Best Overall Response | partial response | 0 Participants |
| Schedule B BI 847325 12 mg (B2) | Best Overall Response | stable disease | 0 Participants |
| Schedule B BI 847325 12 mg (B2) | Best Overall Response | complete response | 0 Participants |
| Schedule B BI 847325 12 mg (B2) | Best Overall Response | not evaluable | 0 Participants |
| Schedule B BI 847325 23 mg (B3) | Best Overall Response | progressive disease | 1 Participants |
| Schedule B BI 847325 23 mg (B3) | Best Overall Response | not evaluable | 0 Participants |
| Schedule B BI 847325 23 mg (B3) | Best Overall Response | stable disease | 0 Participants |
| Schedule B BI 847325 23 mg (B3) | Best Overall Response | complete response | 0 Participants |
| Schedule B BI 847325 23 mg (B3) | Best Overall Response | partial response | 0 Participants |
| Schedule B BI 847325 46 mg (B4) | Best Overall Response | partial response | 0 Participants |
| Schedule B BI 847325 46 mg (B4) | Best Overall Response | progressive disease | 1 Participants |
| Schedule B BI 847325 46 mg (B4) | Best Overall Response | stable disease | 0 Participants |
| Schedule B BI 847325 46 mg (B4) | Best Overall Response | not evaluable | 0 Participants |
| Schedule B BI 847325 46 mg (B4) | Best Overall Response | complete response | 0 Participants |
| Schedule B BI 847325 90 mg (B5) | Best Overall Response | not evaluable | 0 Participants |
| Schedule B BI 847325 90 mg (B5) | Best Overall Response | complete response | 0 Participants |
| Schedule B BI 847325 90 mg (B5) | Best Overall Response | stable disease | 2 Participants |
| Schedule B BI 847325 90 mg (B5) | Best Overall Response | partial response | 0 Participants |
| Schedule B BI 847325 90 mg (B5) | Best Overall Response | progressive disease | 1 Participants |
| Schedule B BI 847325 180 mg (B6) | Best Overall Response | stable disease | 2 Participants |
| Schedule B BI 847325 180 mg (B6) | Best Overall Response | partial response | 0 Participants |
| Schedule B BI 847325 180 mg (B6) | Best Overall Response | progressive disease | 0 Participants |
| Schedule B BI 847325 180 mg (B6) | Best Overall Response | complete response | 0 Participants |
| Schedule B BI 847325 180 mg (B6) | Best Overall Response | not evaluable | 1 Participants |
| Schedule B BI 847325 130 mg (B7) | Best Overall Response | partial response | 0 Participants |
| Schedule B BI 847325 130 mg (B7) | Best Overall Response | progressive disease | 1 Participants |
| Schedule B BI 847325 130 mg (B7) | Best Overall Response | not evaluable | 1 Participants |
| Schedule B BI 847325 130 mg (B7) | Best Overall Response | stable disease | 4 Participants |
| Schedule B BI 847325 130 mg (B7) | Best Overall Response | complete response | 0 Participants |
| Schedule B BI 847325 150 mg (B8) | Best Overall Response | stable disease | 2 Participants |
| Schedule B BI 847325 150 mg (B8) | Best Overall Response | partial response | 0 Participants |
| Schedule B BI 847325 150 mg (B8) | Best Overall Response | progressive disease | 4 Participants |
| Schedule B BI 847325 150 mg (B8) | Best Overall Response | not evaluable | 0 Participants |
| Schedule B BI 847325 150 mg (B8) | Best Overall Response | complete response | 0 Participants |
| Schedule A Total (Total A) | Best Overall Response | partial response | 1 Participants |
| Schedule A Total (Total A) | Best Overall Response | complete response | 0 Participants |
| Schedule A Total (Total A) | Best Overall Response | progressive disease | 24 Participants |
| Schedule A Total (Total A) | Best Overall Response | stable disease | 11 Participants |
| Schedule A Total (Total A) | Best Overall Response | not evaluable | 11 Participants |
| Schedule B Total (Total B) | Best Overall Response | stable disease | 10 Participants |
| Schedule B Total (Total B) | Best Overall Response | not evaluable | 2 Participants |
| Schedule B Total (Total B) | Best Overall Response | progressive disease | 10 Participants |
| Schedule B Total (Total B) | Best Overall Response | partial response | 0 Participants |
| Schedule B Total (Total B) | Best Overall Response | complete response | 0 Participants |
| Total Patients | Best Overall Response | not evaluable | 13 Participants |
| Total Patients | Best Overall Response | stable disease | 21 Participants |
| Total Patients | Best Overall Response | progressive disease | 34 Participants |
| Total Patients | Best Overall Response | complete response | 0 Participants |
| Total Patients | Best Overall Response | partial response | 1 Participants |
Secondary
Disease Control
Disease control was a best overall response of complete response, partial response or stable disease, recorded between the start of treatment and the earliest of disease progression, death, or the end of treatment. Some patients excluded from TS as they were not evaluable for determination of maximum tolerated dose. Thus the number of evaluable TS patients are not the same as the number of original TS patients.
Time frame: From the start of treatment to the earliest of disease progression, death, or the end of treatment. The data cut-off date is 29-Nov-2013.
Population: TS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Schedule A BI 847325 6 mg (A1) | Disease Control | Disease control: Yes | 0 Participants |
| Schedule A BI 847325 6 mg (A1) | Disease Control | Disease control: No | 3 Participants |
| Schedule A BI 847325 9 mg (A2) | Disease Control | Disease control: Yes | 0 Participants |
| Schedule A BI 847325 9 mg (A2) | Disease Control | Disease control: No | 3 Participants |
| Schedule A BI 847325 13 mg (A3) | Disease Control | Disease control: No | 2 Participants |
| Schedule A BI 847325 13 mg (A3) | Disease Control | Disease control: Yes | 1 Participants |
| Schedule A BI 847325 19 mg (A4) | Disease Control | Disease control: Yes | 1 Participants |
| Schedule A BI 847325 19 mg (A4) | Disease Control | Disease control: No | 2 Participants |
| Schedule A BI 847325 26 mg (A5) | Disease Control | Disease control: Yes | 3 Participants |
| Schedule A BI 847325 26 mg (A5) | Disease Control | Disease control: No | 4 Participants |
| Schedule A BI 847325 33 mg (A6) | Disease Control | Disease control: No | 6 Participants |
| Schedule A BI 847325 33 mg (A6) | Disease Control | Disease control: Yes | 1 Participants |
| Schedule A BI 847325 46 mg (A7) | Disease Control | Disease control: No | 3 Participants |
| Schedule A BI 847325 46 mg (A7) | Disease Control | Disease control: Yes | 0 Participants |
| Schedule A BI 847325 63 mg (A8) | Disease Control | Disease control: No | 2 Participants |
| Schedule A BI 847325 63 mg (A8) | Disease Control | Disease control: Yes | 1 Participants |
| Schedule A BI 847325 86 mg (A9) | Disease Control | Disease control: No | 4 Participants |
| Schedule A BI 847325 86 mg (A9) | Disease Control | Disease control: Yes | 1 Participants |
| Schedule A BI 847325 120 mg (A10) | Disease Control | Disease control: No | 4 Participants |
| Schedule A BI 847325 120 mg (A10) | Disease Control | Disease control: Yes | 2 Participants |
| Schedule A BI 847325 160 mg (A11) | Disease Control | Disease control: Yes | 2 Participants |
| Schedule A BI 847325 160 mg (A11) | Disease Control | Disease control: No | 2 Participants |
| Schedule B BI 847325 6 mg (B1) | Disease Control | Disease control: No | 1 Participants |
| Schedule B BI 847325 6 mg (B1) | Disease Control | Disease control: Yes | 0 Participants |
| Schedule B BI 847325 12 mg (B2) | Disease Control | Disease control: Yes | 0 Participants |
| Schedule B BI 847325 12 mg (B2) | Disease Control | Disease control: No | 1 Participants |
| Schedule B BI 847325 23 mg (B3) | Disease Control | Disease control: Yes | 0 Participants |
| Schedule B BI 847325 23 mg (B3) | Disease Control | Disease control: No | 1 Participants |
| Schedule B BI 847325 46 mg (B4) | Disease Control | Disease control: Yes | 0 Participants |
| Schedule B BI 847325 46 mg (B4) | Disease Control | Disease control: No | 1 Participants |
| Schedule B BI 847325 90 mg (B5) | Disease Control | Disease control: No | 1 Participants |
| Schedule B BI 847325 90 mg (B5) | Disease Control | Disease control: Yes | 2 Participants |
| Schedule B BI 847325 180 mg (B6) | Disease Control | Disease control: No | 1 Participants |
| Schedule B BI 847325 180 mg (B6) | Disease Control | Disease control: Yes | 2 Participants |
| Schedule B BI 847325 130 mg (B7) | Disease Control | Disease control: Yes | 4 Participants |
| Schedule B BI 847325 130 mg (B7) | Disease Control | Disease control: No | 2 Participants |
| Schedule B BI 847325 150 mg (B8) | Disease Control | Disease control: No | 4 Participants |
| Schedule B BI 847325 150 mg (B8) | Disease Control | Disease control: Yes | 2 Participants |
| Schedule A Total (Total A) | Disease Control | Disease control: Yes | 12 Participants |
| Schedule A Total (Total A) | Disease Control | Disease control: No | 35 Participants |
| Schedule B Total (Total B) | Disease Control | Disease control: No | 12 Participants |
| Schedule B Total (Total B) | Disease Control | Disease control: Yes | 10 Participants |
| Total Patients | Disease Control | Disease control: No | 47 Participants |
| Total Patients | Disease Control | Disease control: Yes | 22 Participants |
Secondary
Objective Response
Objective response was a best overall response of complete or partial response, recorded between the start of treatment and the earliest of disease progression, death, or the end of treatment. Some patients excluded from TS as they were not evaluable for determination of maximum tolerated dose. Thus the number of evaluable TS patients are not the same as the number of original TS patients.
Time frame: From the start of treatment and the earliest of disease progression, death, or the end of treatment. The data cut-off date is 29-Nov-2013.
Population: TS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Schedule A BI 847325 6 mg (A1) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule A BI 847325 6 mg (A1) | Objective Response | Objective response: No | 3 Participants |
| Schedule A BI 847325 9 mg (A2) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule A BI 847325 9 mg (A2) | Objective Response | Objective response: No | 3 Participants |
| Schedule A BI 847325 13 mg (A3) | Objective Response | Objective response: No | 3 Participants |
| Schedule A BI 847325 13 mg (A3) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule A BI 847325 19 mg (A4) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule A BI 847325 19 mg (A4) | Objective Response | Objective response: No | 3 Participants |
| Schedule A BI 847325 26 mg (A5) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule A BI 847325 26 mg (A5) | Objective Response | Objective response: No | 7 Participants |
| Schedule A BI 847325 33 mg (A6) | Objective Response | Objective response: No | 7 Participants |
| Schedule A BI 847325 33 mg (A6) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule A BI 847325 46 mg (A7) | Objective Response | Objective response: No | 3 Participants |
| Schedule A BI 847325 46 mg (A7) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule A BI 847325 63 mg (A8) | Objective Response | Objective response: No | 3 Participants |
| Schedule A BI 847325 63 mg (A8) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule A BI 847325 86 mg (A9) | Objective Response | Objective response: No | 5 Participants |
| Schedule A BI 847325 86 mg (A9) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule A BI 847325 120 mg (A10) | Objective Response | Objective response: No | 6 Participants |
| Schedule A BI 847325 120 mg (A10) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule A BI 847325 160 mg (A11) | Objective Response | Objective response: Yes | 1 Participants |
| Schedule A BI 847325 160 mg (A11) | Objective Response | Objective response: No | 3 Participants |
| Schedule B BI 847325 6 mg (B1) | Objective Response | Objective response: No | 1 Participants |
| Schedule B BI 847325 6 mg (B1) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule B BI 847325 12 mg (B2) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule B BI 847325 12 mg (B2) | Objective Response | Objective response: No | 1 Participants |
| Schedule B BI 847325 23 mg (B3) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule B BI 847325 23 mg (B3) | Objective Response | Objective response: No | 1 Participants |
| Schedule B BI 847325 46 mg (B4) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule B BI 847325 46 mg (B4) | Objective Response | Objective response: No | 1 Participants |
| Schedule B BI 847325 90 mg (B5) | Objective Response | Objective response: No | 3 Participants |
| Schedule B BI 847325 90 mg (B5) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule B BI 847325 180 mg (B6) | Objective Response | Objective response: No | 3 Participants |
| Schedule B BI 847325 180 mg (B6) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule B BI 847325 130 mg (B7) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule B BI 847325 130 mg (B7) | Objective Response | Objective response: No | 6 Participants |
| Schedule B BI 847325 150 mg (B8) | Objective Response | Objective response: No | 6 Participants |
| Schedule B BI 847325 150 mg (B8) | Objective Response | Objective response: Yes | 0 Participants |
| Schedule A Total (Total A) | Objective Response | Objective response: Yes | 1 Participants |
| Schedule A Total (Total A) | Objective Response | Objective response: No | 46 Participants |
| Schedule B Total (Total B) | Objective Response | Objective response: No | 22 Participants |
| Schedule B Total (Total B) | Objective Response | Objective response: Yes | 0 Participants |
| Total Patients | Objective Response | Objective response: No | 68 Participants |
| Total Patients | Objective Response | Objective response: Yes | 1 Participants |