A Dose Escalation Study of BIBF 1120 Together With Paclitaxel and Carboplatin in Patients With Advanced Stage Non-small-cell Lung Cancer

Carcinoma, Non-Small-Cell Lung Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02182232
• Other study ID #: 1199.5
• Status: Completed
• Phase: Phase 1
• First received: July 2, 2014
• Last updated: July 17, 2014
• Start date: June 2005

Study information

• Verified date: July 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• BIBF 1120

• Paclitaxel

• Carboplatin

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and intensity of adverse events according to Common Terminology Criteria for Adverse Events (version 3.0) associated with increasing doses of BIBF 1120		up to day 126	No
Primary	Maximum tolerated dose (MTD) of BIBF 1120 in combination with carboplatin and paclitaxel		up to day 21	No
Secondary	Pre-dose plasma concentration (Cpre)		up to day 42	No
Secondary	Objective tumor response according to response evaluation criteria in solid tumors (RECIST)		up to 12 months	No
Secondary	Time from best response to onset of tumor progression		Up to 12 months	No
Secondary	Time from start of treatment to time of documented tumor progression		Up to 12 months	No
Secondary	area under the curve (AUC) from 0 to 12 hours (AUC0-12)		up to day 42	No
Secondary	AUC from 0 to the last quantifiable drug concentration (AUC0-tz)		up to day 42	No
Secondary	Maximum plasma concentration (Cmax)		up to day 42	No
Secondary	Time to maximum plasma concentration (tmax)		up to day 42	No
Secondary	Rate constant (?z) for BIBF 1120		up to day 42	No
Secondary	AUC from 0 to 24 hours (AUC0-24) for paclitaxel		up to day 42	No
Secondary	AUC from 0 extrapolated to 48 hours (AUC0-48) for paclitaxel		up to day 42	No
Secondary	AUC from 0 extrapolated to infinity (AUC0-8)		up to day 42	No
Secondary	Percentage of AUC0-8 that is obtained by extrapolation (% AUCtz-8)		up to day 42	No
Secondary	Terminal half-life (t1/2)		up to day 42	No
Secondary	Mean residence time after intravenous administration (MRTiv) for paclitaxel and carboplatin		up to day 42	No
Secondary	Total Clearance (CL/F)		up to day 42	No
Secondary	Volume of distribution during the terminal phase (Vz)		up to day 42	No
Secondary	AUC from 0 to 24 hours (AUC0-24) for carboplatin		Day 1 and 22 in the treatment time	No
Secondary	Plasma concentration 21 hours after start of infusion (C21) for carboplatin		up to day 42	No
Secondary	Plasma concentration 24 hours after start of infusion (C24) for paclitaxel		up to day 42	No

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