Study of Bavituximab in Patients With Advanced Solid Tumor Malignancies - Full Text View

Purpose

The purpose of this study is to determine the safety of bavituximab when administered via a vein, and to examine how bavituximab behaves in the body - how quickly it is taken up by the body and how long it stays there. The effect of bavituximab on tumor responses will also be examined.

Condition	Intervention	Phase
Tumors	Drug: Bavituximab	Phase 1

Peregrine Pharmaceuticals has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Multicenter, Open-Label Safety and Pharmacokinetics Study of Chimeric Anti-Phosphatidylserine Monoclonal Antibody (Bavituximab) in Patients With Refractory Advanced Solid Tumor Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Peregrine Pharmaceuticals:

Primary Outcome Measures:

adverse events [ Time Frame: Study Completion ] [ Designated as safety issue: Yes ]
laboratory evaluations [ Time Frame: Study Completion ] [ Designated as safety issue: Yes ]
human anti-chimeric antibody [ Time Frame: Study Completion ] [ Designated as safety issue: Yes ]
pharmacokinetic analysis [ Time Frame: Study Completion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

tumor evaluation by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Study Completion ] [ Designated as safety issue: No ]

Estimated Enrollment:	28
Study Start Date:	June 2005
Study Completion Date:	August 2009
Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 0.1 mg/kg	Drug: Bavituximab Bavituximab is a sterile drug solution supplied in glass bottles. Bavituximab will be intravenously administered over approximately 90 minutes on days 0, 7, 14 and 21 (dosage determined based on dose cohort and body weight).
Experimental: 2 0.3 mg/kg	Drug: Bavituximab Bavituximab is a sterile drug solution supplied in glass bottles. Bavituximab will be intravenously administered over approximately 90 minutes on days 0, 7, 14 and 21 (dosage determined based on dose cohort and body weight).
Experimental: 3 1 mg/kg	Drug: Bavituximab Bavituximab is a sterile drug solution supplied in glass bottles. Bavituximab will be intravenously administered over approximately 90 minutes on days 0, 7, 14 and 21 (dosage determined based on dose cohort and body weight).
Experimental: 4 3 mg/kg	Drug: Bavituximab Bavituximab is a sterile drug solution supplied in glass bottles. Bavituximab will be intravenously administered over approximately 90 minutes on days 0, 7, 14 and 21 (dosage determined based on dose cohort and body weight).

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00129337

Locations

United States, Arizona
Arizona Cancer Center
Tucson, Arizona, United States, 85724
United States, California
Premiere Oncology
Santa Monica, California, United States, 90404
United States, Tennessee
The West Clinic
Memphis, Tennessee, United States, 38120
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Scott & White Hospital, Center for Cancer Prevention and Care
Temple, Texas, United States, 76508

Sponsors and Collaborators

Peregrine Pharmaceuticals

Investigators

Principal Investigator:	Nuhad Ibrahim, MD	The University of Texas MD Anderson Cancer Center
Principal Investigator:	Linda Garland, MD	University of Arizona
Principal Investigator:	Lee Rosen, MD	Premiere Oncology, A Medical Corporation (Santa Monica)
Principal Investigator:	Lucas Wong, MD	Scott & White Memorial Hospital
Principal Investigator:	Lee S Schwartzberg, MD, FACP	The West Clinic
Principal Investigator:	David E Gerber, MD	University of Texas Southwestern Medical Center

More Information

No publications provided

Responsible Party:	Jennifer Lai, MBA, CCRA, Peregrine Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00129337 History of Changes
Other Study ID Numbers:	PPHM 0401
Study First Received:	August 10, 2005
Last Updated:	February 28, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Peregrine Pharmaceuticals:

monoclonal antibody
phase 1
solid tumor
anti-angiogenesis
refractory advanced solid tumor malignancy

Additional relevant MeSH terms:

Neoplasms
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013