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Sponsored by: |
Asan Medical Center |
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Information provided by: | Asan Medical Center |
ClinicalTrials.gov Identifier: | NCT00786006 |
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 |
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Metastatic Pancreatic Cancer |
Drug: FOLFIRI.3 Drug: FOLFOX |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study |
Official Title: | Randomized Phase II Trial of FOLFIRI3 vs. FOLFOX in Gemcitabine-Refractory Advanced Pancreatic Cancer |
Estimated Enrollment: | 60 |
Study Start Date: | March 2007 |
Estimated Study Completion Date: | September 2009 |
Estimated Primary Completion Date: | March 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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Arm 1: Experimental
FOLFIRI.3
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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
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Arm 2: Active Comparator
FOLFOX
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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)
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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.
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.
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.
We 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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Jae-Lyun Lee, MD., PhD. | 82-2-3010-5977 | jaelyun@amc.seoul.kr |
Contact: Tae-Won Kim, MD., PhD. | 82-2-3010-3910 | twkimmd@amc.seoul.kr |
Korea, Republic of | |
Asan Medical Center | Recruiting |
Seoul, Korea, Republic of | |
Contact: Jae-Lyun Lee, MD., PhD 82-2-3010-5977 jaelyun@amc.seoul.kr |
Responsible Party: | Asan Medical Center ( Jae-Lyun Lee/Assistant professor ) |
Study ID Numbers: | AMC_P_01 |
Study First Received: | November 4, 2008 |
Last Updated: | December 11, 2008 |
ClinicalTrials.gov Identifier: | NCT00786006 History of Changes |
Health Authority: | Korea: Food and Drug Administration |
pancreatic cancer gemcitabine oxaliplatin |
irinotecan fluorouracil Failure to gemcitabine chemotherapy |
Antimetabolites Digestive System Neoplasms Immunologic Factors Pancreatic Neoplasms Irinotecan Endocrine System Diseases Immunosuppressive Agents Antiviral Agents Oxaliplatin |
Digestive System Diseases Radiation-Sensitizing Agents Fluorouracil Gastrointestinal Neoplasms Pancreatic Diseases Endocrinopathy Gemcitabine Endocrine Gland Neoplasms |
Antimetabolites Anti-Infective Agents Digestive System Neoplasms Antimetabolites, Antineoplastic Immunologic Factors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Pancreatic Neoplasms Physiological Effects of Drugs Endocrine System Diseases Enzyme Inhibitors |
Immunosuppressive Agents Antiviral Agents Pharmacologic Actions Neoplasms Neoplasms by Site Digestive System Diseases Radiation-Sensitizing Agents Therapeutic Uses Pancreatic Diseases Gemcitabine Endocrine Gland Neoplasms |