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Randomized Phase II Study of FOLFOX Versus FOLFIRI.3 in Gemcitabine-refractory Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00786006
Recruitment Status : Completed
First Posted : November 5, 2008
Last Update Posted : December 6, 2011
Information provided by (Responsible Party):
JLee, Asan Medical Center

Brief Summary:
The investigators are to evaluate the efficacy and safety of FOLFOX or FOLFIRI.3 combination chemotherapy as second-line salvage chemotherapy in patients with advanced pancreatic carcinoma.

Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Cancer Drug: FOLFIRI.3 Drug: FOLFOX Phase 2

Detailed Description:

Given the poor response rate, usually less than 20% in gemcitabine-based doublet in the first-line setting for advanced pancreatic cancer, an additional problem in the therapeutic management of this common malignant disease constitutes the need for effective treatment alternatives in patients failing gemcitabine-based chemotherapy. To date, few studies have assessed second-line chemotherapy primarily due to the poor prognosis, and the limited life expectancy in advanced pancreatic cancer after failure first-line chemotherapy, and there has been no established second-line treatment for pancreatic cancer after failure to gemcitabine.

  1. Oxaliplatin combination with 5-FU (FOLFOX)

    Oxaliplatin, diaminocyclohexane-platinum, is an alkylating agent inhibiting DNA replication by forming adducts between two adjacent guanines or guanine and adenine molecules. With regard to the inhibition of DNA synthesis, the adducts of oxaliplatin appear to be more effective than cisplatin adducts. Synergism between oxaliplatin and 5-FU has been demonstrated in vitro, and in vivo. Combination of oxaliplatin and 5-FU has proven effective as first- or second-line treatment for advanced colorectal cancer. After being extensively developed as a treatment for colorectal cancer, the role for oxaliplatin in upper gastrointestinal malignancies including pancreatic cancer is an emerging area of investigation. In preclinical studies, oxaliplatin has cytotoxic activity against pancreatic cancer cell lines. When used as single agent as first-line treatment or as second-line treatment after failure to gemcitabine-based chemotherapy, oxaliplatin has minimal activity against pancreatic cancer. However, when it is used with 5-FU, it produced 10% objective response rate with a 21% of clinical benefit response with minimal toxicities in chemotherapy-naïve patients. In phase II studies as second-line treatment, oxaliplatin with 5-FU is well tolerated and produced a objective response rate of 23.3% with additional 30.0% of patients achieving stable disease. Furthermore, recently Oettle et al. reported that weekly infusional 5FU/LV with oxaliplatin prolongs survival and improves quality of life in advanced pancreatic cancer after gemcitabine failure compared with best supportive care alone.

  2. Irinotecan combination with 5-FU (FOLFIRI.3)

Irinotecan has a strong growth-inhibiting effect on cultured pancreatic adenocarcinoma cells. It is also highly active on pancreatic tumor cells in culture and in xenograft models. Irinotecan monotherapy has been tested in patients with previously untreated pancreatic cancer, yielding response rates of 9-27%. In vitro studies indicate that synergism between irinotecan and 5-FU is sequence dependent, cytotoxicity is being stronger when irinotecan is administered before 5-FU. Recently, French study group reported that FOLFIRI.3 regimen, comprising of irinotecan D1 and D3 with 5-FU for 2 days from D2, has promising activity in chemotherapy-naïve and pretreated patients with advanced pancreatic cancer. The confirmed response rate was 37.5% with a median progression-free survival of 5.6 months. The study also suggested no cross-resistance between gemcitabine and FOLFIRI.3.

The investigators are to evaluate the efficacy and safety of FOLFOX or FOLFIRI.3 combination chemotherapy as second-line salvage chemotherapy in patients with advanced pancreatic carcinoma.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial of FOLFIRI3 vs. FOLFOX in Gemcitabine-refractory Advanced Pancreatic Cancer
Study Start Date : March 2007
Actual Primary Completion Date : March 2009
Actual Study Completion Date : September 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Gemcitabine

Arm Intervention/treatment
Experimental: Arm 1
FOLFIRI.3: Irinotecan 70 mg/m2 (over 60 min) on D1, LV 400 mg/m2 (over 2h) D1, 5-FU 2000 mg/m2 (over 46 hours) from D1, then irinotecan 70 mg/m2(over 60 min) at the end of the 5-FU infusion

Active Comparator: Arm 2
FOLFOX: oxaliplatin 85 mg/m2 (over 120 min) on D1, LV 400 mg/m2 (over 2hour) on D1, 5-FU 400 mg/m2 IVP on D1, 5-FU 2,000 mg/m2 (over 46 hours)

Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: Every 6 weeks ]

Secondary Outcome Measures :
  1. Response rate [ Time Frame: Every 6 weeks ]
  2. Overall survival [ Time Frame: every 6 weeks during treatment and every 2 months after off-treatment ]
  3. Safety [ Time Frame: Every 2 weeks ]
    NCI CTCAE v.3.0

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Pathologically proven pancreatic adenocarcinoma
  2. Age 18 year or older
  3. ECOG performance status of 2 or lower
  4. Documented disease progression while receiving or within 6 months after discontinuing gemcitabine-based first-line or adjuvant chemotherapy
  5. Adequate bone marrow function A. WBCs > 4,000/µL, absolute neutrophil count [ANC]>1,500/µL B. Hemoglobin >9.0 g/dL C. Platelets > 100,000/µL
  6. Adequate kidney function (creatinine<1.5 mg/dL)
  7. Adequate liver function (bilirubin<1.5 mg/dL [< 2.5 mg/dL for obstructive jaundice with adequately decompressed bile duct obstruction], transaminases levels<3 times the upper normal limit, and serum albumin of >2.5 mg/dL)
  8. No serious other medical condition that would preclude treatment

Exclusion Criteria:

  1. Other tumor type than adenocarcinoma
  2. Evidence of GI bleeding or GI obstruction
  3. Presence or history of CNS metastasis
  4. Axial skeletal radiotherapy within 6 months
  5. Neuropathy grade 2 or worse

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00786006

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Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of
Sponsors and Collaborators
Asan Medical Center
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Study Chair: Jae-Lyun Lee, MD, PhD Asan Medical Center

Additional Information:
Publications of Results:
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Responsible Party: JLee, Associate professor, Asan Medical Center Identifier: NCT00786006     History of Changes
Other Study ID Numbers: AMC_P_01
First Posted: November 5, 2008    Key Record Dates
Last Update Posted: December 6, 2011
Last Verified: December 2011
Keywords provided by JLee, Asan Medical Center:
pancreatic cancer
Failure to gemcitabine chemotherapy
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Pancreatic Diseases
Digestive System Diseases
Endocrine System Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors