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

November 2, 2014 updated by: Sung Yong Oh, Dong-A University Hospital

Randomized Phase II Study of FOLFOX Followed by FOLFIRI or Reverse Sequence Treatment in Patients With Advanced or Relapsed Gastric Cancer

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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
Drug: 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
Active Comparator: 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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Response rate by RECIST
Time Frame: 6 month after treatment
6 month after treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
progression free survival
Time Frame: 1 year after start
1 year after start
overall survival
Time Frame: 2 years after start
2 years after start

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dong-A University Hospital

Collaborators

Pusan National University Yangsan Hospital

Investigators

  • Principal Investigator: HYUK-CHAN KWON, M.D.,Ph.D, Dong-A University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Actual)

September 1, 2013

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

June 4, 2010

First Submitted That Met QC Criteria

June 7, 2010

First Posted (Estimate)

June 8, 2010

Study Record Updates

Last Update Posted (Estimate)

November 4, 2014

Last Update Submitted That Met QC Criteria

November 2, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAUH-AGC-10-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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