FOLFOX Followed by FOLFIRI or Reverse Sequence Treatment in Advanced Gastric Cancer (AGC)

NCT ID: NCT01138904

Last Updated: 2014-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2013-09-30

Brief Summary

FOLFOX* followed by FOLFIRI** or reverse sequence treatment regimen have been used as a standard treatment modality in metastatic colorectal cancer.Oxaliplatin and Irinotecan were used for advanced gastric cancer also. The investigators study was designed to evaluate the safety and efficacy of FOLFOX followed by FOLFIRI or reverse sequence treatment regimen as a first-line and second line therapy for patients with relapsed or metastatic gastric cancer similar with colorectal cancer.

*FOLFOX: oxaliplatin followed by leucovorin before bolus 5-FU followed by continuous infusion 5-FU

**FOLFIRI: irinotecan followed by leucovorin before bolus 5-FU followed by continuous infusion 5-FU

Detailed Description

Gastric cancer remains a major public health issue, and is the fourth most common cancer and the second leading cause of cancer deaths worldwide. In Korea, gastric cancer is the most common cancer in men, the second most common cancer in women, and the second leading cause of cancer death. Despite the development of early gastric cancer detection programs, more than two-thirds of patients diagnosed with gastric cancer will develop unresectable disease. Even patients with operable tumors evidence high rates of both local and distant recurrence. In cases of advanced gastric cancer, the median survival rate is 9 to 10 months. Additionally, the overall 5-year survival rate is less than 25% in Korea and Japan.

Several combination regimens of chemotherapy for gastric cancer have been developed, but the survival advantage appears to be marginal, and no worldwide standard regimens have yet been established. Recently, a meta-analysis has been conducted to evaluate the efficacy and tolerability of chemotherapy in patients with advanced gastric cancer. The analysis of chemotherapy versus best supportive care (Hazard Ratio/HR = 0.39, confidence interval (CI) 95% 0.28-0.52) and combination versus single agent, mainly 5-Fluorouracil (5-FU), (HR = 0.83, 95% CI 0.74-0.93) demonstrated significant OS results in favour of chemotherapy and combination chemotherapy. Several chemotherapeutic drugs, including 5-fluorouracil (5-FU), mitomycin C, nitrosoureas, and doxorubicin have evidenced some level of efficacy against advanced gastric cancer. However, the majority of combination chemotherapy regimens for advanced gastric cancer have evidenced overall response rates in a range of 30 to 50% in phase II studies. Furthermore, no new regimens including the use of taxanes or irinotecan have improved either response or survivals in phase II or III trials other than docetaxel, cisplatina and infusional 5-FU (DCF) combination.

Oxaliplatin, a third-generation platinum analogue, is a diaminocyclohexane platinum which forms interstrand DNA adducts, which differ from those formed by cisplatin or carboplatin in terms of their capability to overcome resistance mechanisms. FOLFOX-4 or FOLFOX-6 combination regimen have demonstrated response rate of 38%-50% as a first-line treatment of gastric cancer.

Irinotecan (CPT-11,7-ethyl-10-[4-(1-piperidino)-1-piperidino] is a semi-synthetic plant alkaloid obtained from Camptotheca acuminate of the Nyssaceae family. After conversion to its active metabolite, SN-38, irinotecan acts by inhibiting the eukaryotic enzyme, DNA-topoisomerase I. Single-agent irinotecan has evidenced response rates of 13-23% in cases of advanced gastric cancer. 5-Fluorouracil (5-FU) and Topoisomerase I inhibitor-based regimens have demonstrated a response rate of 20-29%, and have been suggested as a first-line treatment for advanced gastric cancer.

FOLFOX followed by FOLFIRI or reverse sequence treatment regimen have been used as a standard treatment modality in metastatic colorectal cancer.

The study was designed to evaluate the safety and efficacy of FOLFOX followed by FOLFIRI or reverse sequence treatment regimen as a first-line and second line therapy for patients with relapsed or metastatic gastric cancer similar with colorectal cancer.

Conditions

Gastric Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IROX arm: FOLFIRI -> FOLFOX

IROX arm: FOLFIRI -> FOLFOX

FOLFOX REGIMEN

D1 Oxaliplatin 85mg/m2 + 5DW 500ml MIV over 120min D1,D2 Leucovorin 50mg IV Push D1,D2 5-Fluorouracil 400mg/m2 IV Push D1,D2 5-Fluorouracil 600mg/m2 + 5DW 1000ml MIV over 22hr

Every 2 weeks

FOLFILI REGIMEN

D1 Irinotecan 150mg/m2 + 5DW 500ml MIV over 120min D1,D2 Leucovorin 50mg IV Push D1,D2 5-Fluorouracil 400mg/m2 IV Push D1,D2 5-Fluorouracil 600mg/m2 + 5DW 1000ml MIV over 22hr

Group Type: ACTIVE_COMPARATOR

irinotecan, oxaliplatin

Intervention Type: DRUG

OXIR: FOLFOX -> FOLFIRI

IROX: FOLFIRI -> FOLFOX

FOLFOX REGIMEN

D1 Oxaliplatin 85mg/m2 + 5DW 500ml MIV over 120min D1,D2 Leucovorin 50mg IV Push D1,D2 5-Fluorouracil 400mg/m2 IV Push D1,D2 5-Fluorouracil 600mg/m2 + 5DW 1000ml MIV over 22hr

Every 2 weeks

FOLFILI REGIMEN

D1 Irinotecan 150mg/m2 + 5DW 500ml MIV over 120min D1,D2 Leucovorin 50mg IV Push D1,D2 5-Fluorouracil 400mg/m2 IV Push D1,D2 5-Fluorouracil 600mg/m2 + 5DW 1000ml MIV over 22hr

Every 2 weeks

OXIR arm: FOLFIRI -> FOLFOX

OXIR arm: FOLFIRI -> FOLFOX

FOLFOX REGIMEN

D1 Oxaliplatin 85mg/m2 + 5DW 500ml MIV over 120min D1,D2 Leucovorin 50mg IV Push D1,D2 5-Fluorouracil 400mg/m2 IV Push D1,D2 5-Fluorouracil 600mg/m2 + 5DW 1000ml MIV over 22hr

Every 2 weeks

FOLFILI REGIMEN

D1 Irinotecan 150mg/m2 + 5DW 500ml MIV over 120min D1,D2 Leucovorin 50mg IV Push D1,D2 5-Fluorouracil 400mg/m2 IV Push D1,D2 5-Fluorouracil 600mg/m2 + 5DW 1000ml MIV over 22hr

Group Type: ACTIVE_COMPARATOR

oxaliplatin, irinotecan

Intervention Type: DRUG

FOLFOX REGIMEN

D1 Oxaliplatin 85mg/m2 + 5DW 500ml MIV over 120min D1,D2 Leucovorin 50mg IV Push D1,D2 5-Fluorouracil 400mg/m2 IV Push D1,D2 5-Fluorouracil 600mg/m2 + 5DW 1000ml MIV over 22hr

Every 2 weeks

FOLFILI REGIMEN

D1 Irinotecan 150mg/m2 + 5DW 500ml MIV over 120min D1,D2 Leucovorin 50mg IV Push D1,D2 5-Fluorouracil 400mg/m2 IV Push D1,D2 5-Fluorouracil 600mg/m2 + 5DW 1000ml MIV over 22hr

Every 2 weeks

Interventions

irinotecan, oxaliplatin

OXIR: FOLFOX -> FOLFIRI

IROX: FOLFIRI -> FOLFOX

FOLFOX REGIMEN

D1 Oxaliplatin 85mg/m2 + 5DW 500ml MIV over 120min D1,D2 Leucovorin 50mg IV Push D1,D2 5-Fluorouracil 400mg/m2 IV Push D1,D2 5-Fluorouracil 600mg/m2 + 5DW 1000ml MIV over 22hr

Every 2 weeks

FOLFILI REGIMEN

D1 Irinotecan 150mg/m2 + 5DW 500ml MIV over 120min D1,D2 Leucovorin 50mg IV Push D1,D2 5-Fluorouracil 400mg/m2 IV Push D1,D2 5-Fluorouracil 600mg/m2 + 5DW 1000ml MIV over 22hr

Every 2 weeks

Intervention Type: DRUG

oxaliplatin, irinotecan

FOLFOX REGIMEN

D1 Oxaliplatin 85mg/m2 + 5DW 500ml MIV over 120min D1,D2 Leucovorin 50mg IV Push D1,D2 5-Fluorouracil 400mg/m2 IV Push D1,D2 5-Fluorouracil 600mg/m2 + 5DW 1000ml MIV over 22hr

Every 2 weeks

FOLFILI REGIMEN

D1 Irinotecan 150mg/m2 + 5DW 500ml MIV over 120min D1,D2 Leucovorin 50mg IV Push D1,D2 5-Fluorouracil 400mg/m2 IV Push D1,D2 5-Fluorouracil 600mg/m2 + 5DW 1000ml MIV over 22hr

Every 2 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed gastric cancer
• No prior chemotherapy for palliative setting
• ECOG PS <3
• Measurable lesion on CT
• adequate kidney function (CCr ≥ 40 ml/min)
• adequate liver function (Transaminase < 3 X upper normal value, Bilirubin < 2 mg%)
• adequate BM function (ANC > 1500/ul, platelet > 75000/ul)
• informed consent

Exclusion Criteria

• other cancer history
• pregnant or breast feeding
• inadequate general condition for chemotherapy
• allergy to oxaliplatin or irinotecan

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pusan National University Yangsan Hospital

OTHER

Sponsor Role: collaborator

Dong-A University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Sung Yong Oh

Department of internal medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

HYUK-CHAN KWON, M.D.,Ph.D

Role: PRINCIPAL_INVESTIGATOR

Dong-A University

Locations

Sung Yong Oh

Busan, , South Korea

Countries

South Korea

Other Identifiers

DAUH-AGC-10-1

Identifier Type: -

Identifier Source: org_study_id