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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
43
BIBF 1120 Medium dose bid + docetaxel 60 mg/m2
BIBF 1120 Medium dose bid + docetaxel 75mg/m2
BIBF 1120 HIgh dose bid + docetaxel 75 mg/m2
1199.29.002 Boehringer Ingelheim Investigational Site
Fukuoka, Fukuoka, Japan
1199.29.001 Boehringer Ingelheim Investigational Site
Osaka-Sayamashi, Osaka, Japan
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
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
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)
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)
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BIBF 1120 Low dose bid + docetaxel 60 mg/m2
BIBF 1120 HIgh dose bid + docetaxel 60 mg/m2
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)
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)
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
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
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
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
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
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
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