Back to resultsA Phase 1b Study With Volociximab in Combination With Carboplatin and Paclitaxel in First-line, Advanced Non-Small Cell Lung Cancer (NSCLC)
Primary Purpose
Non-small Cell Lung Cancer
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
M200 (Volociximab), Carboplatin, Paclitaxel
Sponsored by
About this trial
This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring cancer, carcinoma, chemotherapy, monoclonal antibody therapy, anti-angiogenesis
Eligibility 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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Escalating doses of volociximab at 10, 20, and 30 (or 15) mg/kg with carboplatin and paclitaxel.
Outcomes
Primary Outcome Measures
To determine the maximum tolerated dose (MTD) of volociximab given at different doses in combination with carboplatin and paclitaxel
Secondary Outcome Measures
Pharmacokinetics of volociximab
Efficacy of volociximab in combination with carboplatin/paclitaxel
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00654758
Brief Title
A Phase 1b Study With Volociximab in Combination With Carboplatin and Paclitaxel in First-line, Advanced Non-Small Cell Lung Cancer (NSCLC)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2012
Overall Recruitment Status
Completed
Study Start Date
December 2007 (undefined)
Primary Completion Date
May 2010 (Actual)
Study Completion Date
May 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
cancer, carcinoma, chemotherapy, monoclonal antibody therapy, anti-angiogenesis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Escalating doses of volociximab at 10, 20, and 30 (or 15) mg/kg with carboplatin and paclitaxel.
Intervention Type
Drug
Intervention Name(s)
M200 (Volociximab), Carboplatin, Paclitaxel
Other Intervention Name(s)
Volociximab (M200)
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Pharmacokinetics of volociximab
Time Frame
Approximately 2.5 years
Title
Efficacy of volociximab in combination with carboplatin/paclitaxel
Time Frame
Approximately 2.5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mihail Obrocea, MD
Organizational Affiliation
Abbott
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
22904239
Citation
Besse B, Tsao LC, Chao DT, Fang Y, Soria JC, Almokadem S, Belani CP. Phase Ib safety and pharmacokinetic study of volociximab, an anti-alpha5beta1 integrin antibody, in combination with carboplatin and paclitaxel in advanced non-small-cell lung cancer. Ann Oncol. 2013 Jan;24(1):90-6. doi: 10.1093/annonc/mds281. Epub 2012 Aug 16.
Results Reference
result
Learn more about this trial
A Phase 1b Study With Volociximab in Combination With Carboplatin and Paclitaxel in First-line, Advanced Non-Small Cell Lung Cancer (NSCLC)
We'll reach out to this number within 24 hrs