Capecitabine and Irinotecan in Treating Patients With Locally Advanced, Recurrent, or Metastatic Colorectal Cancer

Roche

Status and phase: Completed; Phase 2

Conditions: Colorectal Cancer

Treatments: Drug: Capecitabine; Drug: Irinotecan

Study type: Interventional

Funder types: Industry

Identifiers

NCT00022698

ML16323

Details and patient eligibility

About

PURPOSE: Phase II trial to study the effectiveness of combining capecitabine and irinotecan in treating patients who have locally advanced, recurrent, or metastatic colorectal cancer.

Full description

OBJECTIVES:

Primary:

• Determine the overall objective response rate in patients with locally advanced, locally recurrent, or metastatic colorectal cancer treated with capecitabine and irinotecan.

Secondary:

• Determine the time to treatment failure, time to overall response, duration of overall response, duration of overall complete response, and time to progression in patients treated with this regimen.
• Determine the 1-year survival and overall survival of patients treated with this regimen.
• Determine the toxicity and safety profile of this regimen in these patients.
• Determine the feasibility of predicting responses to this regimen by the molecular profile of tumor tissue in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive oral capecitabine twice daily on days 2-15 and irinotecan IV over 90 minutes on days 1 and 8. Treatment repeats every 3 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients maintaining a response or stable disease after 12 courses may continue treatment at the discretion of the investigator.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study within 9 months.

Enrollment: 67 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed locally advanced, locally recurrent, or metastatic colorectal adenocarcinoma

• At least 1 measurable lesion

  • At least 10 mm by spiral CT scan
  • At least 20 mm by conventional techniques
  • Bone metastases, ascites, or pleural effusions are not considered measurable disease

• No evidence of CNS metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 80-100%

Life expectancy:

• Not specified

Hematopoietic:

• Neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.25 times upper limit of normal (ULN)
• ALT and AST no greater than 2.5 times ULN (5 times ULN if liver metastases present)
• Alkaline phosphatase no greater than 2.5 times ULN (5 times ULN if liver metastases present or 10 times ULN if bone metastases present)
• No known Gilbert's disease

Renal:

• Creatinine no greater than 1.5 times ULN
• Creatinine clearance at least 50 mL/min

Cardiovascular:

• No clinically significant cardiac disease
• No congestive heart failure
• No symptomatic coronary artery disease
• No cardiac arrhythmias uncontrolled with medication
• No myocardial infarction within the past 12 months

Gastrointestinal:

• Able to swallow tablets
• No lack of physical integrity of the upper gastrointestinal tract
• No malabsorption syndrome

Other:

• No prior unanticipated severe reaction to fluoropyrimidine therapy
• No hypersensitivity to fluorouracil
• No history of uncontrolled seizures or CNS disorders
• No psychological illness or condition that would preclude study entry
• No other malignancy within the past 5 years except curatively treated basal cell skin cancer or carcinoma in situ of the cervix
• No serious infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 12 months since prior neoadjuvant or adjuvant, active or passive immunotherapy
• No concurrent active or passive immunotherapy (e.g., 17-1A antibody) for colon cancer
• No concurrent prophylactic hematopoietic growth factors

Chemotherapy:

• At least 12 months since prior neoadjuvant or adjuvant cytotoxic chemotherapy
• No prior chemotherapy for metastatic colorectal cancer
• No prior therapy with irinotecan or capecitabine
• No other concurrent cytotoxic agents

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy
• No prior radiotherapy to measurable lesion (newly arising lesions in a previously irradiated area allowed)
• No concurrent radiotherapy

Surgery:

• At least 4 weeks since prior major surgery and recovered
• No prior organ allograft

Other:

• At least 4 weeks since prior participation in an investigational drug study
• No other concurrent investigational drugs

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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67 participants in 2 patient groups

Cohort 1,Initial Regimen:(Capecitabine + Irinotecan )

Experimental group

Description:

Participants will receive capecitabine (Xeloda) 1000 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 125 mg/m\^2 as a 90-minute intravenous (IV) infusion on Day 1 and Day 8, every 3 weeks. A total of 12 cycles of treatment will be administered. At the discretion of the investigator, participants who are responding or whose disease is stable will be permitted to continue capecitabine/irinotecan combination therapy until progressive disease is documented in the post-study treatment phase. Participants not participating in post-study treatment will be followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).

Treatment:

Drug: Irinotecan

Drug: Capecitabine

Cohort 2,Amended Regimen:(Capecitabine + Irinotecan)

Experimental group

Description:

Participants will receive capecitabine 900 mg/m\^2, orally, twice daily, for 14 days (Day 2 through Day 15) every 3 weeks, along with irinotecan 100 mg/m\^2 as a 90-minute intravenous (IV) infusion on Day 1 and Day 8, every 3 weeks. A total of 12 cycles of treatment will be administered. At the discretion of the investigator, participants who will be responding or whose disease is stable will be permitted to continue capecitabine/irinotecan combination therapy until progressive disease is documented in the post-study treatment phase. Participants not participating in post-study treatment will be followed every 3 months until time of death, loss to follow-up, or until median survival had been reached (whichever occurred first).

Treatment:

Drug: Irinotecan

Drug: Capecitabine