Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials
Trial record 1 of 1 for:    00486460
Previous Study | Return to List | Next Study

Phase III Trial of Gemcitabine, Curcumin and Celebrex in Patients With Advance or Inoperable Pancreatic Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2007 by Tel-Aviv Sourasky Medical Center.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Tel-Aviv Sourasky Medical Center
ClinicalTrials.gov Identifier:
NCT00486460
First received: June 13, 2007
Last updated: NA
Last verified: June 2007
History: No changes posted
  Purpose

Pancreatic cancer is an aggressive disease with an extremely poor prognosis. It is the forth leading cause of cancer-related fatalities, with an estimated one-year and five-year survival rate of 21% and 5%, respectively. Despite recent progress, the median survival time is 6-10 months for patients with locally advanced disease and 3-6 months for metastatic disease (1). The anti-metabolite gemcitabine has become the standard chemotherapy for locally advanced and metastatic pancreatic cancer, after demonstrating an improved rate of clinical benefit response and an overall survival advantage over 5-FU (2). In addition to its clinical effectiveness gemcitabine has a manageable toxicity profile, making it an attractive agent to investigate in combination with newer agents. Series of phase III trials were conducted examining the efficacy of the combination of gemcitabine and a second cytotoxic agent, including 5-FU, cisplatin, oxaliplatin and irinotecan. These gemcitabine doublets demonstrated no survival advantage over single-agent gemcitabine (3-6). However, the rationale for continuing to study gemcitabine-based combinations remains compelling.

Curcumin (diferuloylmethane) is a natural compound derived from the rhizome of Curcuma Longa, an East Indian plant, commonly called turmeric. It has been shown to possess potent anti-inflammatory and anti-oxidative properties, for which it has a long history of dietary use as a food additive. Curcumin has also a potent anti-proliferative effects against a variety of cancer cell lines in vitro, which stem from its ability to modulate many intracellular signal transduction pathways (7). Human phase I-II studies found curcumin to be safe, and indicated no dose-limiting toxicity when taken by mouth at doses up to 10 g/day (8, 9). This data, together with the dismal therapeutic options available for pancreatic cancer patients, suggest that curcumin warrants investigation in this setting. Investigators from MD Anderson Cancer Center and Rambam Medical Center in Haifa, have recently initiated, separately, a phase II study of single agent Curcumin in patients with pancreatic cancer (10).

One of the lessons learned from cancer research in recent decades is that combination strategies can provide dramatic improvement in a therapy’s safety and efficacy over mono-therapeutic regiments, especially if the combined drugs differ in their mode of action. In a recent paper that was accepted for publication we demonstrated, in vitro, the mechanism, clinical importance and implications of a novel combinatorial therapy, of celecoxib and curcumin, that was discovered in our lab, in inhibiting the growth of several pancreatic cell lines. P-34 (expressing high levels of COX -2), MiaPaca (Expressing low levels of COX-2) and Panc-1 (no expression of COX -2) cell lines were exposed to different concentrations of celecoxib (0-40µM), curcumin (0-20µM) and their combination. In P-34 cells, curcumin synergistically potentiated the inhibitory effect of celecoxib on cell growth. The growth inhibition was associated with inhibition of proliferation and induction of apoptosis.

These experiments further demonstrate, for the first time, that the combination effect is correlated with synergistic augmentation of apoptosis and involves down-regulation of COX-2 protein.

The present study evaluates gemcitabine in combination with curcumin and celecoxib for patients with pancreatic cancer.


Condition Intervention Phase
Pancreatic Cancer
Drug: Gemcitabine
Drug: Curcumin
Drug: Celebrex
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double-Blind

Resource links provided by NLM:


Further study details as provided by Tel-Aviv Sourasky Medical Center:

Study Start Date: June 2005
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Criteria

Inclusion Criteria:

  • Locally advanced or metastatic adenocarcinoma of the pancreas, confirmed by histology or cytology.
  • No prior chemotherapy for pancreatic cancer.
  • Performance status 0-2 (ECOG scale).
  • Age ≥ 18 y.
  • Adequate hematologic function (ANC ≥ 1500/mm³, platelet count ≥ 100,000/mm³).
  • Adequate hepatic function (total bilirubin ≤ 2.0xUNL and AST, ALT and AP ≤ 5.0xUNL)
  • Adequate renal function (creatinine ≤ 2.0).
  • Signed informed consent.

Exclusion Criteria:

  • A history of treated or active central nervous system involvement by the tumor or active neurological disease.
  • Prior radiation. Patients with disease outside the irradiation field or documented disease progression of previously irradiated disease are eligible.
  • Unstable medical condition, including uncontrolled diabetes mellitus or hypertension, active infection, unstable CHF, uncontrolled arrhythmias or unstable coagulation disorders.
  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: NCT00486460

Contacts
Contact: Arie Figer, M.D 03-5260119 arifiger@tasmc.health.gov.il

Locations
Israel
Sourasky Medical Center Recruiting
Tel Aviv, Israel, 64239
Contact: Nadir Arber, M.D, MSc, MHA    03-6953179    nadir@tasmc.health.gov.il   
Sponsors and Collaborators
Tel-Aviv Sourasky Medical Center
Investigators
Principal Investigator: Arber Nadir, M.D, Msc, MHA University of Tel Aviv
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00486460     History of Changes
Other Study ID Numbers: TASMC-07-NA-132-CTIL
Study First Received: June 13, 2007
Last Updated: June 13, 2007
Health Authority: Israel: The Israel National Institute for Health Policy Research and Health Services Research

Keywords provided by Tel-Aviv Sourasky Medical Center:
Locally advanced or metastatic adenocarcinoma of the
pancreas
confirmed by histology or cytology
Inoperatable

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Site
Pancreatic Diseases
Curcumin
Gemcitabine
Analgesics
Analgesics, Non-Narcotic
Anti-Infective Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Antiviral Agents
Central Nervous System Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Sensory System Agents

ClinicalTrials.gov processed this record on November 27, 2014