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)
18 Years
N/A
Both
Non-small Cell Lung Cancer
Trial Information
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)
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.
Inclusion Criteria
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.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
To determine the maximum tolerated dose (MTD) of volociximab given at different doses in combination with carboplatin and paclitaxel
Outcome Time Frame:
Dose escalation phase of the trial
Safety Issue:
Yes
Principal Investigator
Mihail Obrocea, MD
Investigator Role:
Study Director
Investigator Affiliation:
Abbott
Authority:
United States: Food and Drug Administration
Study ID:
M200-1211
NCT ID:
NCT00654758
Start Date:
December 2007
Completion Date:
May 2010
Related Keywords:
- Non-Small Cell Lung Cancer
- cancer
- carcinoma
- chemotherapy
- monoclonal antibody therapy
- anti-angiogenesis
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
Name | Location |
|---|---|
| Site Reference ID/Investigator# 70404 | Hershey, Pennsylvania 17033-0850 |
