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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00217711
• Other study ID #: SAKK 41/03
• Secondary ID: EU-20524
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 20, 2005
• Last updated: June 2, 2012
• Start date: May 2005
• Est. completion date: October 2011

Study information

• Verified date: June 2012
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: October 2011
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Capecitabine
capecitabine
• irinotecan hydrochloride
irinotecan hydrochloride
• oxaliplatin
oxaliplatin

Locations

Country	Name	City	State
Switzerland	Kantonsspital Graubuenden	Chur
Switzerland	Hopital Cantonal Universitaire de Geneve	Geneva
Switzerland	Hirslanden Klinik Aarau	Lausanne
Switzerland	City Hospital Triemli	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Country where clinical trial is conducted

Switzerland, 

References & Publications (1)

von Moos R, Roth A, Ruhstaller T, Widmer L, Uhlmann C, Cathomas R, Köberle D, Simcock M, Lanz D, Popescu R. Oxaliplatin, irinotecan and capecitabine (OCX) for first-line treatment of advanced/metastatic colorectal cancer: a phase I trial (SAKK 41/03). Onk — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	capecitabine + oxaliplatin + irinotecan dose finding	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)	30 days	Yes
Primary	Efficacy of Oxaliplatin, Irinotecan, and Capecitabine	Determine the efficacy of this regimen in these patients (Phase II)	2 months	No
Secondary	Objective response (CR or PR) as measured after completion of study treatment		2 months	No
Secondary	Adverse events as measured after completion of study treatment		2 months	Yes
Secondary	Time to progression		life-long	No
Secondary	Time to treatment failure as measured after completion of study treatment		life-long	No
Secondary	Overall survival		life-long	No