Study of CellCept for Advanced Pancreatic Cancer

Phase I Study of CellCept for Advanced Pancreatic Cancer

Mycophenolate Mofetil (CellCept) is an FDA approved, well tolerated, oral medication used to prevent the body's immune system from attacking transplanted organs. It has never been studied in patients with pancreatic cancer but some preliminary studies have shown that it may antagonize tumor growth. The goals of this study are to find out how much of this drug can safely be taken by patients with advanced pancreatic cancer and to assess the variation of the level of the drug in the blood. Patients will take the drug twice a day at a given dose and the safety of the drug will be monitored through patient symptoms and blood tests. The disease burden will be assessed by radiographic studies at the beginning and end of the study. The patient will take the drug for a total of eight weeks.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Mycophenolate mofetil

Detailed Description

Mycophenolate Mofetil (CellCept) is a prodrug whose active metabolite, mycophenolic acid (MPA), acts as an immune suppressant by inhibiting de novo guanosine synthesis. CellCept is FDA approved to prevent rejection of transplanted organs. It is well tolerated, orally dosed, and has some known antitumor effects. It has never been studied in pancreatic cancer and the maximum tolerated dose is not known. In vitro studies in our lab with human pancreatic cancer lines found that MPA was a potent inhibitor of pancreatic cancer cell growth and induced apoptosis. The objectives of this study are to identify the maximum tolerated dose of CellCept in patients with advanced pancreatic cancer that have failed at least two prior chemotherapy regimens and assess its pharmacokinetics.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of pancreas.
• Disease stage IV, locally advanced and/or metastatic.
• Measurable disease: Any mass reproducibly measurable in two perpendicular diameters by x-ray, physical examination, CT or MRI scan.

• The following lesions conventionally are not considered measurable:

  • CNS lesions
  • Blastic or lytic bone lesions (which will be documented and followed)
  • Radiated lesions unless progression after RT is documented
• Ineligible for other high priority national or institutional studies.

• Prior therapy allowed:

  • Chemotherapy (at least one prior regimen)
  • > 3 weeks since last chemotherapy
  • > 3 weeks since surgery
  • ≥ 4 weeks since RT
• Non pregnant, non lactating women with a negative serum α-HCG test within one week of starting the study, AND
• Must be willing to consent to the use of two forms of contraception (at least one barrier) if of childbearing potential while on trial and six weeks after CellCept has been stopped.

• Clinical Parameters:

  • Life expectancy ≥ 3 months
  • Age 18 to 70 years
  • Brain CT or MRI no visible metastases
  • Performance status 0-2 (ECOG- see appendix B)
  • HIV negative or never tested

• Required initial laboratory data:

  • Normal
  • White cell count ≥3000 cells / μl
  • Platelet count ≥100,000 platelets / μl
  • BUN ≤1.5 x normal 20 mg/dl
  • Creatinine ≤1.5 x normal 1.0 mg/dl
  • Total Bilirubin ≤3.0 mg/dl
  • AST, ALT ≤3.0 x normal 38 U/L
  • Alkaline Phosphatase ≤3.0 x normal 96 U/L
  • Albumin ≥2.5 g/dl
• Informed Consent: Each patient must be completely aware of the nature of his/her disease process and must willingly give written consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, adverse effects, risks, and discomforts.
• Prior malignancy in last 5 years: The cancer must be curatively treated carcinoma in situ of the cervix or skin cancer.
• No serious medical or psychiatric illness preventing informed consent or intensive treatment (e.g., serious infection).
• Absence of concurrent treatment with cholestyramine, acyclovir, cyclosporine, or antacids with magnesium or aluminum hydroxides because of their effects on drug metabolism and serum levels of MPA.
• Absence of active serious digestive system disease as defined at the discretion of the Principal Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CellCept; Administered in tablet form twice daily one hour after eating.	Drug: Mycophenolate mofetil; Dose escalation increasing successively from 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, and 5.0 grams p.o. bid. Each patient will be treated for eight weeks (56 days).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Identification of maximum tolerated dose of CellCept in patients with advanced pancreatic cancer	8 weeks

Collaborators and Investigators

• Sponsor: Columbia University

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: October 14, 2009
• First Submitted That Met QC Criteria: October 16, 2009
• First Posted (Estimate): October 20, 2009

Study Record Updates

• Last Update Posted (Estimate): April 25, 2014
• Last Update Submitted That Met QC Criteria: April 24, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: AAAA1127