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

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 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Paclitaxel Carboplatin

U.S. FDA Resources

Further study details as provided by Abbott:

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 escalation phase of the trial ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Pharmacokinetics of volociximab [ Time Frame: Approximately 2.5 years ] [ Designated as safety issue: No ]
Efficacy of volociximab in combination with carboplatin/paclitaxel [ Time Frame: Approximately 2.5 years ] [ Designated as safety issue: No ]

Enrollment:	33
Study Start Date:	December 2007
Study Completion Date:	May 2010
Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 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. Other Name: Volociximab (M200)

Arms

Assigned Interventions

Experimental: 1

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.

Other Name: Volociximab (M200)

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

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 > or = 6 months prior to Cycle 1, Day 1 of this study.
Eastern Cooperative Oncology Group (ECOG) performance status < or =1.
A negative pregnancy test (serum or urine) in women of childbearing potential at screening.

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, > or =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
Site Reference ID/Investigator# 70404
Hershey, Pennsylvania, United States, 17033-0850
France
Site Reference ID/Investigator# 70403
Villejuif, France, 94805

Sponsors and Collaborators

Abbott

Investigators

Study Director:

Mihail Obrocea, MD

Abbott

More Information

No publications provided

Responsible Party:	Abbott
ClinicalTrials.gov Identifier:	NCT00654758 History of Changes
Other Study ID Numbers:	M200-1211, 2007-003396-39
Study First Received:	April 4, 2008
Last Updated:	April 25, 2012
Health Authority:	United States: Food and Drug Administration France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) France: Institutional Ethical Committee

Keywords provided by Abbott:

cancer
carcinoma
chemotherapy
monoclonal antibody therapy
anti-angiogenesis

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carboplatin
Paclitaxel

Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 17, 2013