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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
JLee, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT00786006
First received: November 4, 2008
Last updated: December 5, 2011
Last verified: December 2011
  Purpose

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 Intervention Phase
Metastatic Pancreatic Cancer
Drug: FOLFIRI.3
Drug: FOLFOX
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial of FOLFIRI3 vs. FOLFOX in Gemcitabine-refractory Advanced Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: every 6 weeks during treatment and every 2 months after off-treatment ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: Every 2 weeks ] [ Designated as safety issue: Yes ]
    NCI CTCAE v.3.0


Enrollment: 61
Study Start Date: March 2007
Study Completion Date: September 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
FOLFIRI.3
Drug: FOLFIRI.3
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
Drug: FOLFOX
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)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00786006

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

Additional Information:
Publications:
Responsible Party: JLee, Associate professor, Asan Medical Center
ClinicalTrials.gov Identifier: NCT00786006     History of Changes
Other Study ID Numbers: AMC_P_01
Study First Received: November 4, 2008
Last Updated: December 5, 2011
Health Authority: Korea: Food and Drug Administration

Keywords provided by Asan Medical Center:
pancreatic cancer
gemcitabine
oxaliplatin
irinotecan
fluorouracil
Failure to gemcitabine chemotherapy

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Site
Pancreatic Diseases
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014