Oxaliplatin, Irinotecan, and Capecitabine in Treating Patients With Advanced or Metastatic Colorectal Cancer That Cannot Be Removed By Surgery

Sponsor

Swiss Group for Clinical Cancer Research (Other)

Overall Status

Completed

CT.gov ID

NCT00217711

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

5.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, irinotecan, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of capecitabine when given together with oxaliplatin and irinotecan and to see how well they work in treating patients with advanced or metastatic colorectal cancer that cannot be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: Capecitabine Drug: irinotecan hydrochloride Drug: oxaliplatin	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Primary

Determine the maximum tolerated dose and recommended phase II dose of capecitabine administered in combination with oxaliplatin and irinotecan in patients with unresectable advanced or metastatic colorectal cancer. (Phase I)
Determine the efficacy of this regimen in these patients. (Phase II)

Secondary

Determine the tolerability of this regimen in these patients. (Phase II)

OUTLINE: This is a multicenter, phase I dose-escalation study of capecitabine followed by a phase II study.

Phase I: Patients receive oxaliplatin IV over 2 hours on days 1 and 15, irinotecan IV over 1 hour on days 8 and 22, and oral capecitabine twice daily on days 1-29. Treatment repeats every 5 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive capecitabine at the MTD and irinotecan and oxaliplatin as in phase I.

After completion of study treatment, patients are followed every 2 months for 1 year and then every 4 months thereafter.

PROJECTED ACCRUAL: A total of 23-32 patients (3-12 for the phase I portion and 20 for the phase II portion) will be accrued for this study within 2.75 years

Study Design

Study Type:

Interventional

Actual Enrollment :

23 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Oxaliplatin, Irinotecan, and Capecitabine as a Combination Regimen for First-Line Treatment of Advanced or Metastatic Colorectal Cancer

Study Start Date :

May 1, 2005

Actual Primary Completion Date :

Aug 1, 2007

Actual Study Completion Date :

Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A Oxaliplatin, Irinotecan, and Capecitabine	Drug: Capecitabine capecitabine Drug: irinotecan hydrochloride irinotecan hydrochloride Drug: oxaliplatin oxaliplatin

Arm

Intervention/Treatment

Active Comparator: Arm A

Oxaliplatin, Irinotecan, and Capecitabine

Drug: Capecitabine

capecitabine

Drug: irinotecan hydrochloride

irinotecan hydrochloride

Drug: oxaliplatin

oxaliplatin

Outcome Measures

Primary Outcome Measures

capecitabine + oxaliplatin + irinotecan dose finding [30 days]
Determine the maximum tolerated dose and recommended phase II dose of capecitabine administered in combination with oxaliplatin and irinotecan in patients with unresectable advanced or metastatic colorectal cancer. (Phase I)
Efficacy of Oxaliplatin, Irinotecan, and Capecitabine [2 months]
Determine the efficacy of this regimen in these patients (Phase II)

Secondary Outcome Measures

Objective response (CR or PR) as measured after completion of study treatment [2 months]
Adverse events as measured after completion of study treatment [2 months]
Time to progression [life-long]
Time to treatment failure as measured after completion of study treatment [life-long]
Overall survival [life-long]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed unresectable advanced or metastatic colorectal cancer
Measurable disease (phase II only)
At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan or MRI
No presence or history of CNS metastases

PATIENT CHARACTERISTICS:

Age

18 to 70

Performance status

WHO 0-1

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Bilirubin ≤ 1.25 times upper limit of normal (ULN) (1.5 times ULN if liver metastases are present)
AST and ALT ≤ 3 times ULN (5 times ULN if liver metastases are present)

Renal

Creatinine clearance > 60 mL/min

Cardiovascular

No New York Heart Association class III-IV congestive heart failure
No symptomatic coronary artery disease
No uncontrolled cardiac arrhythmia
No myocardial infarction within the past year
No other clinically significant cardiac disease

Immunologic

No active autoimmune disease
No uncontrolled infection
No prior severe reaction to fluoropyrimidine therapy or known hypersensitivity to fluorouracil
No known hypersensitivity to any component of study drugs

Other

Not pregnant or nursing
Negative pregnancy test
Patients must use effective contraception during and for 1 year after study participation
No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer
No peripheral neuropathy > grade 1 of any origin (e.g., alcohol or diabetes)
No nausea, vomiting, or malabsorption syndrome that would preclude ingestion or absorption of oral medication
No psychiatric disability that would preclude study compliance
No uncontrolled diabetes
No other serious underlying medical condition that would preclude study participation
No known dihydropyrimidine dehydrogenase deficiency

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent prophylactic hematopoietic growth factors

Chemotherapy

More than 6 months since prior adjuvant fluoropyrimidine chemotherapy
No other prior chemotherapy

Endocrine therapy

Not specified

Radiotherapy

No concurrent radiotherapy
Concurrent radiotherapy of a single painful lesion allowed

Surgery

Not specified

Other

More than 30 days since prior clinical trial participation
No other concurrent experimental drugs
No other concurrent anticancer therapy
No concurrent sorivudine or its chemically-related analogues (e.g., lamivudine)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Kantonsspital Graubuenden	Chur	Switzerland	CH-7000
2	Hopital Cantonal Universitaire de Geneve	Geneva	Switzerland	CH-1211
3	Hirslanden Klinik Aarau	Lausanne	Switzerland	CH-1011
4	City Hospital Triemli	Zurich	Switzerland	CH-8063