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

NCT00666692 | Completed Phase 1 DMC

• 1 other identifier: M200-1212
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Non-small Cell Lung Cancer

Keywords

cancer; carcinoma; monoclonal antibody therapy; anti-angiogenesis

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated dose (MTD) of volociximab given at different doses in combination with carboplatin, paclitaxel, and bevacizumab.

  Dose Limiting Toxicities (DLT) will be assessed during the first treatment cycle for each cohort

Secondary Outcomes (1)

• 1) Pharmacokinetics of volociximab 2) Efficacy of volociximab in combination with carboplatin/paclitaxel and bevacizumab.

  Throughout study period

Study Arms (1)

1

EXPERIMENTAL

Escalating doses of volociximab at 10, 20, and 30 mg/kg with carboplatin, paclitaxel, and bevacizumab

Drug: M200 (Volociximab), Carboplatin, Paclitaxel, Bevacizumab

Interventions

M200 (Volociximab), Carboplatin, Paclitaxel, Bevacizumab DRUG

Volociximab will be administered via IV infusion once every three week at 10, 20, and 15 or 30 mg/kg with an additional loading dose in the 10, 20, and 15 mg/kg dose levels on Day 8 of the first cycle. Volociximab will be given for up to 6 cycles (3 weeks/cycle). Subjects who have stable disease or better and subjects who have disease that is not progressing 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 four drugs, when given in combination, will be infused on the same day in the following sequence: volociximab, paclitaxel, carboplatin.

Also known as: Volociximab (M200)

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females of at least 18 years of age.
• Stage IIIB with pleural effusion or Stage IV non-squamous 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. Male subjects and female subjects of childbearing potential must be willing to practice effective contraception during the study and be willing and able to continue contraception for 6 months after the last dose of study drug.
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) (in accordance with national and local subject privacy regulations).

You may not qualify if:

• Histological evidence of predominantly squamous cell carcinoma.
• Known central nervous system (CNS) metastases.
• 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 \<10 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.

Sponsors & Collaborators

• Abbott: lead

Study Sites (4)

Site Reference ID/Investigator# 70354

Bethesda, Maryland, 20817-7847, United States

Location

Site Reference ID/Investigator# 70333

Hershey, Pennsylvania, 17033-0850, United States

Location

Site Reference ID/Investigator# 70355

Greenville, South Carolina, 29605, United States

Location

Site Reference ID/Investigator# 70353

Yakima, Washington, 98902, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms; Carcinoma

Interventions

volociximab; Carboplatin; Paclitaxel; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Mihail Obrocea, MD

  Abbott

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2008
• First Posted: April 25, 2008
• Study Start: April 1, 2008
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: April 27, 2012

Record last verified: 2012-04

Locations

US (4)