A Multicenter, Open-Label Safety and Pharmacokinetics Study of Chimeric Anti-Phosphatidylserine Monoclonal Antibody (Bavituximab) in Patients With Refractory Advanced Solid Tumor Malignancies
18 Years
N/A
Both
Tumors
Trial Information
A Multicenter, Open-Label Safety and Pharmacokinetics Study of Chimeric Anti-Phosphatidylserine Monoclonal Antibody (Bavituximab) in Patients With Refractory Advanced Solid Tumor Malignancies
The genetic variations observed in most advanced cancers decrease the effectiveness of many
anti-cancer agents through the development of drug resistance. Therefore, alternative
approaches to the direct targeting of cancer cells are urgently needed. Bavituximab is the
generic name for a chimeric (human/murine) monoclonal antibody directed against
aminophospholipids. Bavituximab is Peregrine's first investigational product under its
anti-phospholipid therapy technology platform. Anti-phospholipid therapy is a novel approach
to treating cancer. It is based on the finding that aminophospholipids, which are basic
components of the inner surface of cells become externally exposed in response to certain
disease states such as cancer. Laboratory and animal studies have demonstrated that
bavituximab specifically targets cancer cells and inhibits tumor growth in a variety of
experimental cancer models. This study will examine the safety and tolerability of
bavituximab when administered to patients with advanced solid tumor cancers that are
unresponsive to current therapies. Cohorts of 6 patients each will be treated at the
starting dose of 0.1 mg bavituximab per kilogram body weight (0.1 mg/kg). Successive patient
cohorts will receive 0.3, 1.0 and 3.0 mg/kg of bavituximab. Patients will be followed for a
total of 56 days. Patients who demonstrate an objective tumor response will be offered
further bavituximab treatment on an extension protocol.
Inclusion Criteria:
- At least 18 years of age with life expectancy of 3 months
- Evaluable, histologically or cytologically confirmed, refractory advanced solid tumor
malignancy
- ECOG score of less than or equal to 1
- Adequate hematologic function (absolute neutrophil count [ANC] greater than or equal
to 1,500 cells/uL; hemoglobin greater than or equal to 9 g/dL; platelets greater than
or equal to 100,000/uL and less than or equal to 500,000/uL)
- Adequate renal function (serum creatinine less than or equal to 1.5 mg/dL or
calculated creatinine clearance greater than 60 mL/min)
- Adequate hepatic function (bilirubin less than or equal to 1.5 x ULN; ALT less than
or equal to 3 x ULN; AST less than or equal to 3 x ULN)
- Normal coagulation profile (prothrombin time/international normalized ratio [PT/INR]
and activated partial thromboplastin time [aPTT] within institutional normal limits)
- D-dimer less than or equal to 2 times upper limit of institutional normal
- New York Heart Association classification I or II for patients with significant
cardiopulmonary disease
- Female patients must have a negative serum pregnancy test at prestudy and all
patients of reproductive potential must be willing to use an approved form of barrier
method contraception
Exclusion Criteria:
- Prior exposure to any chimeric antibody
- Any evidence of clinically significant bleeding
- Known history of bleeding diathesis or coagulopathy
- Any history of thromboembolic events including central venous catheter-related
thrombosis within the past 12 months
- Any evidence or history of hypercoagulable state (eg, shortened aPTT)
- Concurrent therapy with oral or parenteral anticoagulants
- Concurrent hormone therapy (ie, estrogen contraceptives, hormone replacement,
anti-estrogen)
- Chemotherapy, immunotherapy or radiotherapy within 4 weeks of day 0 (6 weeks for
nitrosoureas and mitomycin C) or have not recovered from treatment-related side
effects due to agents administered more than 4 weeks earlier (stable,
non-hematological residual toxicities of Grade 1 or less and Grade 2 dry skin or
alopecia are allowed)
- Investigational therapy within 4 weeks of day 0
- Evidence of central nervous system (CNS) metastatic disease at prestudy (no active
brain metastases on magnetic resonance imaging [MRI] at prestudy)
- Major surgery within 4 weeks of day 0
- Pregnant or nursing women
- Uncontrolled intercurrent disease (eg, diabetes, hypertension, thyroid disease)
- Any history of angina pectoris, coronary artery disease or cerebrovascular accident,
or transient ischemic attack
- A history of any condition requiring anti-platelet therapy with the exception of
general cardiovascular prophylaxis with aspirin
- A history of any condition requiring treatment (past or current) with coumarin-type
agents within the past 12 months
- Cardiac arrhythmia requiring medical therapy
- Serious non-healing wound
- Requirement for chronic daily treatment with non-steroidal anti-inflammatory drugs
(NSAIDs), anti-platelet drugs (eg, phosphodiesterase inhibitors, adenosine
diphosphate receptor antagonists) or steroids
- Known chronic infection with HIV or hepatitis
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
adverse events
Outcome Time Frame:
Study Completion
Safety Issue:
Yes
Principal Investigator
Nuhad Ibrahim, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
The University of Texas MD Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
PPHM 0401
NCT ID:
NCT00129337
Start Date:
June 2005
Completion Date:
August 2009
Related Keywords:
- Tumors
- monoclonal antibody
- phase 1
- solid tumor
- anti-angiogenesis
- refractory advanced solid tumor malignancy
- Neoplasms
Name | Location |
|---|---|
| Arizona Cancer Center | Tucson, Arizona 85724 |
| MD Anderson Cancer Center | Houston, Texas 77030-4096 |
| University of Texas Southwestern Medical Center | Dallas, Texas |
| The West Clinic | Memphis, Tennessee 38120 |
| Premiere Oncology | Santa Monica, California 90404 |
| Scott & White Hospital, Center for Cancer Prevention and Care | Temple, Texas 76508 |
