Combination of CPT-11 and LoHP vs Combination of 5-FU, Leucovorin and LoHP as 1st Line Treatment in Gastric Patients

Sponsor

Hellenic Oncology Research Group (Other)

Overall Status

Completed

CT.gov ID

NCT00447967

Collaborator

University Hospital of Crete (Other)

110

Enrollment

Locations

Arms

Duration (Months)

13.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II trial will compare the efficacy and toxicity of the combination of Irinotecan and Oxaliplatin versus 5-FU/LV and Oxaliplatin as first line treatment in patients with locally advanced or metastatic gastric cancer

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer	Drug: Irinotecan Drug: Oxaliplatin Drug: Fluorouracil Drug: Leucovorin Drug: Oxaliplatin	Phase 2

Detailed Description

There is no regimen considered standard in advanced gastric cancer. The reported response rates of 5-FU-based combination chemotherapy are higher than single agents (10-50%) but more toxic. The combination of 5-FU/LV and LOHP has demonstrated an ORR of 43%, median TTP of approximately 6,5 months and OS of 8,6 months in phase II trials, with an acceptable toxicity.

Irinotecan (CPT-11) is effective as salvage treatment in metastatic gastric cancer and has a synergistic activity with LOHP in preclinical trials

Study Design

Study Type:

Interventional

Anticipated Enrollment :

110 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase II Study of Irinotecan and Oxaliplatin Versus the Combination of 5-FU/LV and Oxaliplatin, as First-Line Treatment in Patients With Locally Advanced or Metastatic Gastric Cancer

Study Start Date :

Jul 1, 2004

Actual Primary Completion Date :

Sep 1, 2008

Actual Study Completion Date :

Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 IOX	Drug: Irinotecan Irinotecan 200 mg/m2 IV on Day 1 every 3 weeks for 6 cycles Other Names: CPT-11 Drug: Oxaliplatin Oxaliplatin 80 mg/m2 IV on Day 2 every 3 weeks for 6 cycles Other Names: LoHP
Experimental: 2 FLOX	Drug: Fluorouracil Fluorouracil 400 mg/m2 infused over 10 min IV and Fluorouracil600 mg/m2 infused over 22 hours IV, Day 1 and 2 (De Grammont regimen)every 2 weeks for 12 cycles Other Names: 5-FU Drug: Leucovorin Leucovorin 200 mg/m2 infused over 1 hour IV on day 1 and day 2 (De Grammont regimen) every 2 weeks for 12 cycles Other Names: LV Drug: Oxaliplatin Oxaliplatin 85 mg/m2 as a 4 hour IV infusion, Day 1 every 4 weeks for 6 cycles Other Names: LoHP

Arm

Intervention/Treatment

Experimental: 1

IOX

Drug: Irinotecan

Irinotecan 200 mg/m2 IV on Day 1 every 3 weeks for 6 cycles

Other Names:

CPT-11

Drug: Oxaliplatin

Oxaliplatin 80 mg/m2 IV on Day 2 every 3 weeks for 6 cycles

Other Names:

LoHP

Experimental: 2

FLOX

Drug: Fluorouracil

Fluorouracil 400 mg/m2 infused over 10 min IV and Fluorouracil600 mg/m2 infused over 22 hours IV, Day 1 and 2 (De Grammont regimen)every 2 weeks for 12 cycles

Other Names:

5-FU

Drug: Leucovorin

Leucovorin 200 mg/m2 infused over 1 hour IV on day 1 and day 2 (De Grammont regimen) every 2 weeks for 12 cycles

Other Names:

Drug: Oxaliplatin

Oxaliplatin 85 mg/m2 as a 4 hour IV infusion, Day 1 every 4 weeks for 6 cycles

Other Names:

LoHP

Outcome Measures

Primary Outcome Measures

Objective Response Rates [Objective responses confirmed by CT or MRI (on 3rd and 6th cy)]

Secondary Outcome Measures

Time to progression [1 year]
Toxicity [Toxicity assessment on each chemotherapy cycle]
Overall survival [1 year]
Quality of life [Assessment every two cycles]
Symptoms improvement [Assessment every two cycles]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed locally advanced or metastatic gastric cancer.
Measurable or evaluable disease.
Measurable disease is defined as at least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or 1 bidimensionally measurable lesion ≥ 20 X 10 mm. Lesions that are smaller or uni- or bidimensionally unmeasurable are considered as evaluable disease.
Previous adjuvant chemotherapy with Irinotecan, Oxaliplatin and/or 5-FU based regimen. Patients who relapse within the first 6 months after the completion of adjuvant treatment are not eligible for the study.
Karnofsky performance status > 70%.
Age ≥18 years.
Adequate liver (Bilirubin ≤ 1.5 UNL, SGOT/SGPT ≤ 4 UNL, ALP ≤ 2.5 UNL), renal (Creatinine ≤ 1.5 UNL) and bone marrow (ANC ≥ 1,500/mm3, PLT ≥ 100,000/mm3) function.
Patients must be able to understand the nature of this study and give written informed consent.

Exclusion Criteria:

Active infection
History of serious cardiac disease (unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, ventricular arrhythmias)
Previous radiotherapy within the last 4 weeks or > 25% of bone marrow.
Patients with CNS metastases
Patients with chronic diarrhea (at least for 3 months) or partial bowel obstruction.
Malnutrition or loss of > 10% of body weight during the last month.
Peripheral neuropathy ≥ grade 2
Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer.
Psychiatric illness or social situation that would preclude study compliance.
Pregnant or lactating women.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital of Crete	Heraklion	Crete	Greece	71110
2	University General Hospital of Alexandroupolis, Dep of Medical Oncology	Alexandroupolis		Greece
3	"IASO" General Hospital of Athens, 1st Dep of Medical Oncology	Athens		Greece
4	"Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine	Athens		Greece
5	401 Military Hospital of Athens	Athens		Greece
6	Air Forces Military Hospital of Athens	Athens		Greece
7	State General Hospital of Larissa	Larissa		Greece
8	"Metaxa's" Anticancer Hospital of Piraeus, 1st Dep of Medical Oncology	Piraeus		Greece