Monoclonal Antibody RAV12 and Gemcitabine in Treating Patients With Metastatic Pancreatic Cancer

This study has been terminated.
(Corporate decision)
Sponsor:
Information provided by (Responsible Party):
MacroGenics
ClinicalTrials.gov Identifier:
NCT00625586
First received: February 26, 2008
Last updated: November 20, 2012
Last verified: November 2012
  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: RAV12 plus gemcitabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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:


Further study details as provided by MacroGenics:

Primary Outcome Measures:
  • Proportion of Patients Alive at 8 Months [ Time Frame: 8 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of Patients Alive at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Partial Response and Complete Response Rates [ Time Frame: 8 months ] [ Designated as safety issue: No ]
    Based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.0; partial response = 30% decrease in sum of longest diameter. complete response = 100% decrease in sum of longest diameter. Rate of response = proportion of complete or partial responses based on number of patients evaluated.

  • Progression-free Survival [ Time Frame: time to progression or death, up to 3 years ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: three years ] [ Designated as safety issue: No ]
  • Adverse Events [ Time Frame: any timeframe following study drug up to 3 years ] [ Designated as safety issue: Yes ]
    Frequency of adverse events and serious adverse events

  • Cmax [ Time Frame: 29 days ] [ Designated as safety issue: No ]
    RAV12 and gemcitabine cmax


Enrollment: 2
Study Start Date: March 2008
Study Completion Date: March 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RAV12 plus gemcitabine Biological: RAV12 plus gemcitabine

Initial dose of gemcitabine plus RAV12 at 0.375 mg/kg qw escalated to 0.75 mg/kg qw.

During the efficacy segment, 63 pts were to be treated with gemcitabine 1000 mg/m2 iv over 30 min., weekly days 1, 8, 15, 22 of the first cycle and 1000 mg/m2 iv over 30 min., weekly days 1, 8, and 15 of each subsequent cycle of 28 days plus RAV12 at Maximum Tolerated Dose (MTD) iv days 1; 4 or 5; 8, 11 or 12; and 15, 18 or 19 of each 28-day cycle until progression.

Other Name: gemcitabine: Gemzar

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, carbohydrate antigen 19-9 (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 immunohistochemistry (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 central nervous system (CNS) metastatic disease

PATIENT CHARACTERISTICS:

  • Eastern Cooperative Oncology Group performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9.0 g/dL
  • alanine aminotransferase and aspartate aminotransferase ≤ 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 Papanicolaou 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 New York Heart Association 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
MacroGenics, 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
MacroGenics
Investigators
Study Chair: Stanford Stewart, MD MacroGenics, Incorporated
  More Information

No publications provided

Responsible Party: MacroGenics
ClinicalTrials.gov Identifier: NCT00625586     History of Changes
Other Study ID Numbers: CDR0000587562, RAVENBIO-RV12-2007-003
Study First Received: February 26, 2008
Results First Received: August 20, 2012
Last Updated: November 20, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by MacroGenics:
adenocarcinoma of the pancreas
stage IV pancreatic cancer
recurrent pancreatic cancer

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Site
Pancreatic Diseases
Antibodies, Monoclonal
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014