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

Sponsors and Collaborators:	PDL BioPharma, Inc. Biogen Idec
Information provided by:	PDL BioPharma, Inc.
ClinicalTrials.gov Identifier:	NCT00654758

Purpose

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).

Condition	Intervention	Phase
Non-Small Cell Lung Cancer	Drug: M200 (Volociximab), Carboplatin, Paclitaxel	Phase I

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Carboplatin Paclitaxel Immunoglobulins Globulin, Immune

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety Study
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)

Further study details as provided by PDL BioPharma, Inc.:

Primary Outcome Measures:

To determine the maximum tolerated dose (MTD) of volociximab given at different doses in combination with carboplatin and paclitaxel [ Time Frame: Dose Limiting Toxicities (DLT) will be assessed during the first treatment cycle for each cohort ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Pharmacokinetics of volociximab [ Time Frame: Throughout study period ] [ Designated as safety issue: No ]
Efficacy of volociximab in combination with carboplatin/paclitaxel [ Time Frame: Throughout study period ] [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	December 2007
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	September 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Escalating doses of volociximab at 10, 20, and 30 (or 15) mg/kg with carboplatin and paclitaxel.	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.

Arms

Assigned Interventions

1: Experimental

Escalating doses of volociximab at 10, 20, and 30 (or 15) mg/kg with carboplatin and paclitaxel.

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.

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Key Inclusion Criteria:

Males and females at least 18 years of age.
Stage IIIB or IV or recurrent NSCLC.
Measurable and/or evaluable disease according to RECIST.
No prior chemotherapy, biological therapy or immunotherapy for Stage IIIB/IV disease. Adjuvant therapy for early stage disease must have been completed ≥6 months prior to Cycle 1, Day 1 of this study.
Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
A negative pregnancy test (serum or urine) in women of childbearing potential at screening.

Key Exclusion Criteria:

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.
Absolute neutrophil count (ANC) <1500/mm3, hemoglobin level <9 g/dL, or a platelet count <100,000/mm3.
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.
Radiation therapy within 1 month before Cycle 1, Day 1.
Documented symptomatic central nervous system (CNS) tumor or CNS metastases.
History of thromboembolic events, including cardiovascular or cerebrovascular events (ie, acute myocardial infarction [AMI], stroke) within 1 year prior to Cycle 1, Day 1.
History of known bleeding disorders and coagulation defects.
History of significant hemoptysis (ie, ≥1/2 teaspoon red blood per event) or gastrointestinal bleeding within 1 year prior to Cycle 1, Day 1.
Major surgery (eg, exploratory laparotomy) within 4 weeks prior to Cycle 1, Day 1 of the study.
Clinically significant or unstable medical conditions including, but not limited to, uncontrolled diabetes mellitus requiring insulin, uncontrolled hypertension, or uncontrolled or symptomatic orthostatic hypotension.
Oxygen-dependent chronic obstructive pulmonary disease.
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.
Prior bone marrow or stem cell transplant.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00654758

Locations

United States, Pennsylvania
Penn State Milton S. Hershey Medical Center	Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Becky Miller 717-531-1003 rmiller13@hmc.psu.edu
Principal Investigator: Chandra P Belani, MD
France
Institut de cancerologie Gustave Roussy	Recruiting
Villejuif cedex, France, 94805
Contact: Maud Martin +33 1 42 11 61 73 maud.martin@igr.fr
Principal Investigator: Benjamin Besse, MD

Sponsors and Collaborators

PDL BioPharma, Inc.

Biogen Idec

Investigators

Principal Investigator:	Chandra P Belani, MD	Milton S. Hershey Medical Center
Principal Investigator:	Benjamin Besse, MD	Institut de cancerologie Gustave Roussy

More Information

Responsible Party:	PDL BioPharma, Inc. ( Jill Henrich, Executive Director, Regulatory Affairs )
Study ID Numbers:	M200-1211
Study First Received:	April 4, 2008
Last Updated:	August 11, 2008
ClinicalTrials.gov Identifier:	NCT00654758
Health Authority:	United States: Food and Drug Administration; France: Afssaps - French Health Products Safety Agency; France: Institutional Ethical Committee

Keywords provided by PDL BioPharma, Inc.:

cancer
carcinoma
chemotherapy
monoclonal antibody therapy
anti-angiogenesis

Study placed in the following topic categories:

Thoracic Neoplasms
Non-small cell lung cancer
Carboplatin
Carcinoma
Antibodies, Monoclonal
Antibodies
Respiratory Tract Diseases

Lung Neoplasms
Paclitaxel
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Immunoglobulins

Additional relevant MeSH terms:

Respiratory Tract Neoplasms
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

Therapeutic Uses
Mitosis Modulators
Tubulin Modulators
Antimitotic Agents
Antineoplastic Agents, Phytogenic
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009