A Phase 1b Study With Volociximab in Combination With Carboplatin and Paclitaxel in First-line, Advanced Non-Small Cell Lung Cancer (NSCLC)

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase 1b Trial to Evaluate the Safety and Pharmacokinetics of Volociximab (M200) in Combination With Carboplatin and Paclitaxel in Subjects With Previously Untreated Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00654758
• Other study ID #: M200-1211
• Secondary ID: 2007-003396-39
• Status: Completed
• Phase: Phase 1
• First received: April 4, 2008
• Last updated: November 17, 2017
• Start date: December 2007
• Est. completion date: May 2010

Study information

• Verified date: April 2012
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to examine the safety of volociximab in combination with a standard treatment of carboplatin and paclitaxel in subjects previously untreated with chemotherapy for advanced stage (IIIB/IV) non-small cell lung cancer (NSCLC).

Description:

This Phase 1b, multicenter, open-label, dose-escalation study will evaluate the safety and pharmacokinetics (PK) of volociximab in combination with carboplatin and paclitaxel (C/P) as first-line treatment in subjects with Stage IIIB or IV non-small cell lung cancer (NSCLC). Volociximab doses of 10, 20, and 30 mg/kg (or 15 mg/kg if 20 mg/kg is not tolerable) with carboplatin/paclitaxel chemotherapy will be tested for determining the maximum tolerated dose (MTD). Subjects will be dosed once very 3 weeks for up to 6 cycles.

Volociximab is a high-affinity, chimeric monoclonal antibody that specifically binds to α5β1 integrin, a cell-surface receptor for fibronectin. Volociximab blocks the binding of α5β1 to fibronectin, thereby inhibiting a pivotal interaction required for angiogenesis.

More than 170 subjects with various solid tumor types have received volociximab in Phase 1 and Phase 2 single and combination studies. At the doses tested, there has not been a dose limiting toxicity (DLT) or a maximum tolerated dose (MTD) defined.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria

1. Males and females at least 18 years of age.

2. Stage IIIB or IV or recurrent NSCLC.

3. Measurable and/or evaluable disease according to RECIST.

4. No prior chemotherapy, biological therapy or immunotherapy for Stage IIIB/IV disease. Adjuvant therapy for early stage disease must have been completed > or = 6 months prior to Cycle 1, Day 1 of this study.

5. Eastern Cooperative Oncology Group (ECOG) performance status < or =1.

6. A negative pregnancy test (serum or urine) in women of childbearing potential at screening.

Exclusion Criteria

1. Known allergy or sensitivity to murine proteins, chimeric antibodies or other components of the product, Cremophor EL (polyoxyethylated castor oil), cisplatin, or other platinum-containing compounds.

2. Absolute neutrophil count (ANC) <1500/mm3, hemoglobin level <9 g/dL, or a platelet count <100,000/mm3.

3. Aspartate transaminase (AST), alanine transaminase (ALT), or alkaline phosphatase values of .2.5 of the upper limits of normal values (ULN) (>5 ULN for subjects with liver metastases) or alkaline phosphatase values >2.5 ULN (unless documented bone metastases are responsible for the increase of alkaline phosphatase); total bilirubin >1.5 mg/dL, or serum creatinine >1.8 mg/dL.

4. Radiation therapy within 1 month before Cycle 1, Day 1.

5. Documented symptomatic central nervous system (CNS) tumor or CNS metastases.

6. History of thromboembolic events, including cardiovascular or cerebrovascular events (ie, acute myocardial infarction [AMI], stroke) within 1 year prior to Cycle 1, Day 1.

7. History of known bleeding disorders and coagulation defects.

8. History of significant hemoptysis (ie, > or =1/2 teaspoon red blood per event) or gastrointestinal bleeding within 1 year prior to Cycle 1, Day 1.

9. Major surgery (eg, exploratory laparotomy) within 4 weeks prior to Cycle 1, Day 1 of the study.

10. Clinically significant or unstable medical conditions including, but not limited to, uncontrolled diabetes mellitus requiring insulin, uncontrolled hypertension, or uncontrolled or symptomatic orthostatic hypotension.

11. Oxygen-dependent chronic obstructive pulmonary disease.

12. Known active infections requiring intravenous (IV) antibiotics, antivirals, or antifungals, including but not limited to chronic human immunodeficiency virus, hepatitis B, or hepatitis C infection.

13. Prior bone marrow or stem cell transplant.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• M200 (Volociximab), Carboplatin, Paclitaxel
Volociximab will be administered via IV infusion at 10, 20, and 15 or 30 mg/kg with an additional loading dose in the 10, 20, and 15 mg/kg dose levels during the first cycle. Volociximab will be given for at least 6 cycles (3 weeks/cycle) and subjects who have stable disease at the end of 6 cycles may continue to receive volociximab alone until disease progression. Carboplatin is administered via IV infusion and dosed based on the Calvert formula (with a target area AUC of 6 mg/mL/min) for up to 6 cycles (3 weeks/cycle). Paclitaxel is administered via IV infusion and dosed at 200 mg/m2 for up to 6 cycles (3 weeks/cycle). All three drugs, when given in combination, will be infused on the same day in the following sequence: volociximab, paclitaxel, carboplatin.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

References & Publications (1)

Besse B, Tsao LC, Chao DT, Fang Y, Soria JC, Almokadem S, Belani CP. Phase Ib safety and pharmacokinetic study of volociximab, an anti-a5ß1 integrin antibody, in combination with carboplatin and paclitaxel in advanced non-small-cell lung cancer. Ann Oncol — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the maximum tolerated dose (MTD) of volociximab given at different doses in combination with carboplatin and paclitaxel		Dose escalation phase of the trial
Secondary	Pharmacokinetics of volociximab		Approximately 2.5 years
Secondary	Efficacy of volociximab in combination with carboplatin/paclitaxel		Approximately 2.5 years