Monoclonal Antibody RAV12 and Gemcitabine in Treating Patients With Metastatic Pancreatic Cancer - Full Text View

Sponsored by:	Raven Biotechnologies
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00625586

Purpose

RATIONALE: Monoclonal antibodies, such as RAV12, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving RAV12 together with gemcitabine may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and best dose of monoclonal antibody RAV12 when given together with gemcitabine in treating patients with metastatic pancreatic cancer.

Condition	Intervention	Phase
Pancreatic Cancer	Biological: monoclonal antibody RAV12 Drug: gemcitabine hydrochloride Genetic: DNA analysis Genetic: polymorphism analysis Other: immunohistochemistry staining method Other: laboratory biomarker analysis Other: pharmacological study	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase 2 Evaluation of the Monoclonal Antibody, RAV12, in Combination With Standard Gemcitabine in the Treatment of Patients With Metastatic Pancreatic Cancer Who Have Not Been Previously Treated for Metastatic Disease

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Gemcitabine Gemcitabine hydrochloride Immunoglobulins Globulin, Immune

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Proportion of patients alive at 8 months after treatment with standard gemcitabine hydrochloride plus RAV12 [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of patients alive at 12 months [ Designated as safety issue: No ]
Partial response and complete response rates [ Designated as safety issue: No ]
Duration of response [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Safety [ Designated as safety issue: Yes ]
Pharmacokinetics of gemcitabine hydrochloride and monoclonal antibody RAV 12 when administered in combination [ Designated as safety issue: No ]

Estimated Enrollment:	81
Study Start Date:	March 2008
Estimated Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

To determine the maximum tolerated dose of monoclonal antibody RAV12 when administered with standard gemcitabine hydrochloride in patients with previously untreated metastatic pancreatic cancer.
To determine the proportion of these patients surviving at 8 months after initiation of this regimen.
To provide point estimates for response rate and duration of response in patients treated with this regimen.
To define the toxicity profile of this drug in these patients when administered with standard gemcitabine hydrochloride.
To estimate, preliminarily, the progression-free survival and overall survival of these patients after treatment with this regimen.
To explore the utility of the tumor marker, CA19-9, in the assessment of these patients.

OUTLINE: This is a dose-escalation study of monoclonal antibody RAV12, followed by an efficacy study. The study is conducted in two segments.

Segment 1 (dose escalation of RAV12): Patients receive gemcitabine hydrochloride IV over 30 minutes on days

1, 8, 15, and 22 of course 1 and on days 1, 8, and 15 of each subsequent course. Patients also receive RAV12 IV once weekly on days 1, 8, and 15 or twice weekly on days 1, 4 or 5, 8, 11 or 12, 15, and 18 or 19 until the maximum tolerated dose (MTD) is reached. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Segment 2 (efficacy): Once the MTD has been determined, patients receive RAV12 at the MTD and gemcitabine hydrochloride as in segment 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Blood samples are obtained for pharmacokinetic sampling during the dose-escalation segment of the study. Samples are analyzed to determine plasma concentrations of RAV12, gemcitabine hydrochloride, and difluorodeoxyuridine.

Blood samples are also examined periodically for expression of serum biomarkers (i.e., CA19-9, RAAG12, and HACA) and for DNA analysis of Fc-gamma receptor polymorphisms. Archival paraffin blocks or slides from biopsy of primary or metastatic deposit or fresh/frozen tissue may be obtained at baseline for additional correlative studies. Samples are analyzed by IHC for expression of RAAG12 and for development of a companion RAAG12 diagnostic assay.

After completion of study therapy, patients are followed every 8 weeks for up to 3 years.

PROJECTED ACCRUAL: This study will accrue a total of 18 patients in the dose-escalation segment and 63 patients in the efficacy segment of the trial.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed adenocarcinoma of the pancreas
- Metastatic disease
  - No prior therapy for metastatic disease (except prior adjuvant chemotherapy and/or radiotherapy)
At least 1 radiographically measurable site of disease ≥ 2 cm in the largest dimension by traditional CT technique or ≥ 1 cm by spiral CT scan (per RECIST)
No known history of current or prior CNS metastatic disease

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 9.0 g/dL
ALT and AST ≤ 2.5 times upper limit of normal (ULN)
Alkaline phosphatase and γ-glutamyltransferase ≤ 2.5 times ULN
Amylase and lipase ≤ 1.5 times ULN
Total bilirubin ≤ 1.5 times ULN
Creatinine < 1.5 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Must be available for study-related treatments and assessments at the treating institution
No known hypersensitivity to any component of gemcitabine hydrochloride
No known hypersensitivity to murine or recombinant proteins, polysorbate 80, or any excipient contained in the drug formulation
No other primary malignancy that has been in remission for ≤ 3 years except treated nonmelanoma skin cancer, biopsy-confirmed carcinoma in situ of the cervix, squamous intraepithelial lesion on PAP smear, localized prostate cancer with Gleason score < 6, or resected melanoma in situ
No other primary malignancy that has a generally accepted recurrence risk ≥ 10%
No active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 4 weeks of enrollment
No history of chronic or recurrent infections that require continuous use of antiviral, antifungal, or antibacterial agents
No serious underlying medical condition that would impair the patient's ability to receive or tolerate the planned treatment at the investigational site, including significant pulmonary compromise or heart disease of NYHA class III or IV
No dementia or altered mental status that would preclude sufficient understanding to provide informed consent

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
More than 4 weeks since prior major surgery
More than 4 weeks since prior and no other concurrent investigational agents
More than 1 week since prior oral antiviral, antifungal, or antibacterial therapy
No concurrent immunosuppressive medications, steroids (except steroid inhaler, ophthalmic solution, nasal spray, or a stable dose of ≤ 10 mg/day of oral prednisone or equivalent), other antineoplastic therapy, or antitumor vaccinations
Monoclonal antibody treatment for non-cancer indications must be completed at least 3 half lives from study entry
No concurrent prophylactic hematologic growth factors
No concurrent megavitamin therapy
No concurrent bisphosphonates

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00625586

Locations

United States, California
Raven Biotechnologies, Incorporated
South San Francisco, California, United States, 94080
United States, Pennsylvania
Fox Chase Cancer Center - Philadelphia
Philadelphia, Pennsylvania, United States, 19111-2497

Sponsors and Collaborators

Raven Biotechnologies

Investigators

Study Chair:

Stanford Stewart, MD

Raven Biotechnologies

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000587562, RAVENBIO-RV12-2007-003
Study First Received:	February 26, 2008
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00625586 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the pancreas
stage IV pancreatic cancer
recurrent pancreatic cancer

Study placed in the following topic categories:

Antimetabolites
Anti-Infective Agents
Digestive System Neoplasms
Immunologic Factors
Pancreatic Neoplasms
Endocrine System Diseases
Immunosuppressive Agents
Antiviral Agents
Pancrelipase
Recurrence
Antibodies, Monoclonal

Antibodies
Digestive System Diseases
Radiation-Sensitizing Agents
Neoplasm Metastasis
Gastrointestinal Neoplasms
Pancreatic Diseases
Endocrinopathy
Adenocarcinoma
Gemcitabine
Immunoglobulins
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Digestive System Neoplasms
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Pancreatic Neoplasms
Physiological Effects of Drugs
Endocrine System Diseases
Enzyme Inhibitors
Immunosuppressive Agents

Antiviral Agents
Pharmacologic Actions
Antibodies, Monoclonal
Neoplasms
Antibodies
Neoplasms by Site
Digestive System Diseases
Radiation-Sensitizing Agents
Therapeutic Uses
Pancreatic Diseases
Gemcitabine
Endocrine Gland Neoplasms

ClinicalTrials.gov processed this record on September 04, 2009