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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2012 by Dong-A University Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Pusan National University Yangsan Hospital
Information provided by (Responsible Party):
Sung Yong Oh, Dong-A University Hospital
ClinicalTrials.gov Identifier:
NCT01138904
First received: June 4, 2010
Last updated: May 5, 2012
Last verified: May 2012
  Purpose

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


Condition Intervention Phase
Gastric Cancer
Drug: irinotecan, oxaliplatin
Drug: oxaliplatin, irinotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Study of FOLFOX Followed by FOLFIRI or Reverse Sequence Treatment in Patients With Advanced or Relapsed Gastric Cancer

Resource links provided by NLM:


Further study details as provided by Dong-A University Hospital:

Primary Outcome Measures:
  • Response rate by RECIST [ Time Frame: 6 month after treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • progression free survival [ Time Frame: 1 year after start ] [ Designated as safety issue: Yes ]
  • overall survival [ Time Frame: 2 years after start ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: September 2009
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01138904

Contacts
Contact: HYUK-CHAN KWON, M.D.,Ph.D. +82-51-240-5044 hckwon@dau.ac.kr
Contact: SUNG YONG OH, M.D.,Ph.D. +82-51-240-2808 drosy@dau.ac.kr

Locations
Korea, Republic of
Sung Yong Oh Recruiting
Busan, Korea, Republic of, 602-715
Contact: HYUK-CHAN KWON, M.D.,Ph.D.    +82-51-240-5044    hckwon@dau.ac.kr   
Contact: SUNG YONG OH, M.D.,Ph.D.    +82-51-240-2808    drosy@dau.ac.kr   
Principal Investigator: HYCK-CHAN KWON, MD         
Sub-Investigator: SUNG YONG OH, MD         
Sub-Investigator: SUEE LEE, MD         
Sub-Investigator: KYUNG-A KWON, MD         
Sub-Investigator: SUNG HYUN KIM, MD         
Principal Investigator: SUNG GUN KIM, MD         
Sponsors and Collaborators
Dong-A University Hospital
Pusan National University Yangsan Hospital
Investigators
Principal Investigator: HYUK-CHAN KWON, M.D.,Ph.D Dong-A University
  More Information

No publications provided

Responsible Party: Sung Yong Oh, Department of internal medicine, Dong-A University Hospital
ClinicalTrials.gov Identifier: NCT01138904     History of Changes
Other Study ID Numbers: DAUH-AGC-10-1
Study First Received: June 4, 2010
Last Updated: May 5, 2012
Health Authority: Korea: Institutional Review Board

Keywords provided by Dong-A University Hospital:
gastric cancer
oxaliplatin
irinotecan
sequential treatment

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Fluorouracil
Oxaliplatin
Irinotecan
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 28, 2014