Clinical trial NCT02182232: A Dose Escalation Study of BIBF 1120 Together With Paclitaxel and Carboplatin in Patients With Advanced Stage Non-small-cell Lung Cancer
Official title: A Phase I Open Label Dose Escalation Study of Continuous Oral Treatment With BIBF 1120 Together With Paclitaxel and Carboplatin in Patients With Advanced Stage Non-small-cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-07-08
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objectives of this trial were to determine the MTD of BIBF 1120 in combination with carboplatin and paclitaxel, pharmacokinetics and objective response of treatment


Eligibility criteria: Inclusion Criteria:

1. Male or female patients with histologically or cytologically confirmed Stage IIIB (including pleural effusion), IV or recurrent NSCLC
2. Bi-dimensionally measurable disease by one or more techniques (CT, MRI, X-ray)
3. Age 18 years or older
4. Life expectancy of at least three (3) months
5. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1
6. Written informed consent that is consistent with ICH-GCP guidelines

Exclusion Criteria:

1. Prior treatment for NSCLC including chemotherapy, biologic response modifier therapy, or any investigational drug
2. Participation in another clinical study within the past four weeks before start of therapy or concomitantly with this study
3. Active brain metastases (stable for \<28 days, symptomatic, or requiring concurrent steroids or antiepileptic therapy)
4. Centrally located tumors with radiologic evidence (CT or MRI) of local invasion of major blood vessels
5. Cavitary or necrotic tumors
6. Sanguinous pleural effusion due to disease or pericardial effusion suspicious for disease
7. Radiotherapy to an area of measurable disease (unless disease progression had been documented following completion of therapy)
8. Radiotherapy within 4 weeks preceding Day 0
9. Other active malignancy diagnosed within the past 3 years (other than non-melanomatous skin cancer)
10. Gastrointestinal abnormalities that would interfere with intake or absorption of the study drug, such as a requirement for intravenous alimentation, prior surgical procedures affecting absorption, treatment for peptic ulcer disease within the last 6 months, active gastrointestinal bleeding unrelated to cancer (as evidenced by either hematemesis, hematochezia, or melena in the past 3 months and without endoscopic documented resolution), or malabsorption syndromes
11. Significant cardiovascular disease (i.e., uncontrolled hypertension, myocardial infarction within 6 months, unstable angina, serious cardiac arrhythmia, ≥NYHA Grade 2 congestive heart failure)
12. History of hemorrhagic or thrombotic event (including transient ischemic attacks) in the past 12 months
13. Clinically significant hemoptysis (1 teaspoon or more) in the past 3 months
14. Concurrent therapeutic anticoagulation (except heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except chronic low-dose daily aspirin \<325 mg)
15. Known hypersensitivity to paclitaxel, carboplatin, or any of their excipients including Cremophor® (polyoxyethylated castor oil)
16. Absolute neutrophil count (ANC) ≤1,500/μl, platelet count ≤100,000/μl, or hemoglobin \<9 gm/dL
17. Total bilirubin \>1.5 mg/dL (26 μmol/L, SI Unit equivalent), alanine amino transferase (ALT) and/or aspartate amino transferase (AST) ≥1.5 X ULN,
18. Serum creatinine \>1.5 mg/dL (\>132 μmol/L, SI Unit equivalent)
19. Persistent hematuria or proteinuria (more than trace)
20. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
21. Pregnancy or breastfeeding
22. Known or suspected active alcohol or drug abuse
23. Patients unable to comply with the protocol

Primary outcomes:
measure: Incidence and intensity of adverse events according to Common Terminology Criteria for Adverse Events (version 3.0) associated with increasing doses of BIBF 1120
timeFrame: up to day 126
measure: Maximum tolerated dose (MTD) of BIBF 1120 in combination with carboplatin and paclitaxel
timeFrame: up to day 21
Secondary outcomes:
measure: Pre-dose plasma concentration (Cpre)
timeFrame: up to day 42
measure: Objective tumor response according to response evaluation criteria in solid tumors (RECIST)
timeFrame: up to 12 months
measure: Time from best response to onset of tumor progression
timeFrame: Up to 12 months
measure: Time from start of treatment to time of documented tumor progression
timeFrame: Up to 12 months
measure: area under the curve (AUC) from 0 to 12 hours (AUC0-12)
timeFrame: up to day 42
measure: AUC from 0 to the last quantifiable drug concentration (AUC0-tz)
timeFrame: up to day 42
measure: Maximum plasma concentration (Cmax)
timeFrame: up to day 42
measure: Time to maximum plasma concentration (tmax)
timeFrame: up to day 42
measure: Rate constant (λz) for BIBF 1120
timeFrame: up to day 42
measure: AUC from 0 to 24 hours (AUC0-24) for paclitaxel
timeFrame: up to day 42
measure: AUC from 0 extrapolated to 48 hours (AUC0-48) for paclitaxel
timeFrame: up to day 42
measure: AUC from 0 extrapolated to infinity (AUC0-∞)
timeFrame: up to day 42
measure: Percentage of AUC0-∞ that is obtained by extrapolation (% AUCtz-∞)
timeFrame: up to day 42
measure: Terminal half-life (t1/2)
timeFrame: up to day 42
measure: Mean residence time after intravenous administration (MRTiv) for paclitaxel and carboplatin
timeFrame: up to day 42
measure: Total Clearance (CL/F)
timeFrame: up to day 42
measure: Volume of distribution during the terminal phase (Vz)
timeFrame: up to day 42
measure: AUC from 0 to 24 hours (AUC0-24) for carboplatin
timeFrame: Day 1 and 22 in the treatment time
measure: Plasma concentration 21 hours after start of infusion (C21) for carboplatin
timeFrame: up to day 42
measure: Plasma concentration 24 hours after start of infusion (C24) for paclitaxel
timeFrame: up to day 42
Other outcomes:
Locations:
Study officials:
References: