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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

Phase 2
18 Years
Not Enrolling
Pancreatic Cancer

Thank you

Trial Information

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


- 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.

Inclusion Criteria


- 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


- 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

- 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

- No dementia or altered mental status that would preclude sufficient understanding to
provide informed consent


- 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

Type of Study:


Study Design:

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

Outcome Measure:

Proportion of Patients Alive at 8 Months

Outcome Time Frame:

8 months

Safety Issue:


Principal Investigator

Stanford Stewart, MD

Investigator Role:

Study Chair

Investigator Affiliation:

MacroGenics, Incorporated


United States: Food and Drug Administration

Study ID:




Start Date:

March 2008

Completion Date:

March 2009

Related Keywords:

  • Pancreatic Cancer
  • adenocarcinoma of the pancreas
  • stage IV pancreatic cancer
  • recurrent pancreatic cancer
  • Pancreatic Neoplasms



Fox Chase Cancer Center - Philadelphia Philadelphia, Pennsylvania  19111-2497
MacroGenics, Incorporated South San Francisco, California  94080