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

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ClinicalTrials.gov Identifier: NCT00625586
Recruitment Status : Terminated (Corporate decision)
First Posted : February 28, 2008
Results First Posted : December 19, 2012
Last Update Posted : December 19, 2012
Sponsor:
Information provided by (Responsible Party):
MacroGenics

Tracking Information
First Submitted Date  ICMJE February 26, 2008
First Posted Date  ICMJE February 28, 2008
Results First Submitted Date  ICMJE August 20, 2012
Results First Posted Date  ICMJE December 19, 2012
Last Update Posted Date December 19, 2012
Study Start Date  ICMJE March 2008
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2012)
Proportion of Patients Alive at 8 Months [ Time Frame: 8 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 26, 2008)
Proportion of patients alive at 8 months after treatment with standard gemcitabine hydrochloride plus RAV12
Change History Complete list of historical versions of study NCT00625586 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2012)
  • Proportion of Patients Alive at 12 Months [ Time Frame: 12 months ]
  • Partial Response and Complete Response Rates [ Time Frame: 8 months ]
    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 ]
  • Overall Survival [ Time Frame: three years ]
  • Adverse Events [ Time Frame: any timeframe following study drug up to 3 years ]
    Frequency of adverse events and serious adverse events
  • Cmax [ Time Frame: 29 days ]
    RAV12 and gemcitabine cmax
Original Secondary Outcome Measures  ICMJE
 (submitted: February 26, 2008)
  • Proportion of Patients Alive at 12 Months
  • Partial response and complete response rates
  • Duration of response
  • Progression-free Survival
  • Overall Survival
  • Safety
  • Pharmacokinetics of gemcitabine hydrochloride and monoclonal antibody RAV 12 when administered in combination
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Monoclonal Antibody RAV12 and Gemcitabine in Treating Patients With Metastatic Pancreatic Cancer
Official Title  ICMJE 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
Brief Summary

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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Cancer
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: RAV12 plus gemcitabine
Intervention: Biological: RAV12 plus gemcitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 18, 2012)
2
Original Enrollment  ICMJE
 (submitted: February 26, 2008)
81
Actual Study Completion Date  ICMJE March 2009
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00625586
Other Study ID Numbers  ICMJE CDR0000587562
RAVENBIO-RV12-2007-003 ( Other Identifier: Macrogenics, Inc. )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MacroGenics
Study Sponsor  ICMJE MacroGenics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Stanford Stewart, MD MacroGenics, Incorporated
PRS Account MacroGenics
Verification Date November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP