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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase II Study of Oral Xeloda (Capecitabine) in Combination With Intravenous Irinotecan for Patients With Locally Advanced and/or Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Capecitabine
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1,Initial Regimen:(Capecitabine + Irinotecan )<br>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). | Drug: Capecitabine<br> <br> Drug: Irinotecan<br> <br> |
| Experimental: Cohort 2,Amended Regimen:(Capecitabine + Irinotecan)<br>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). | Drug: Capecitabine<br> <br> Drug: Irinotecan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response Rate Based on Tumor Measurement as Per Response Evaluation Criteria In Solid Tumors Version 1.0 (RECIST 1.0) | Objective Response Rate (ORR) is defined as the percentage of participants with complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors (RECIST 1.0). CR is defined as the disappearance of all target and non-target lesions and normalization of tumor marker level. PR is defined as a greater than or equal to (>/=) 30% decrease in the sum of the longest diameter (LD) of the target lesions, taking as reference the baseline sum of LD. Participants who did not have a post-baseline tumor measurement were considered non-responders in the assessment of ORR. | Approximately 43 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression | Time to disease progression was assessed as the time from start of treatment to the time the participant was first recorded as having disease progression or died due to causes other than disease progression. If a participant never progressed while being followed, he/she was censored at the date of the last tumor assessment or the date of the last dose if no post-baseline tumor measurement was available. | Approximately 43 Months | 
| Time to Treatment Failure | Time to treatment failure was assessed as the time from start of treatment to the time the participant was withdrawn due to any of the reasons such as adverse events, progressive disease, insufficient therapeutic response, death, failure to return, or refused treatment, did not cooperate or withdrew consent. | Approximately 43 Months | 
| Percentage of Participants With One-year Survival | Survival was measured as the time from start of treatment to the date of death or till one year whichever occurred first. | Up to Month 12 | 
| Overall Survival | Overall Survival is defined as the time from start of treatment to the date of death. Participants who did not die were censored at the last date the participant was known to be alive. | Approximately 43 Months | 
| Time To Objective Response | The time to objective response is defined as the time from start of treatment to the date of first objective response. Participants who never responded during study were censored at the last tumor assessment or the date of last dose, whichever was later, or at the date of death if occurring prior to response. | Approximately 43 Months | 
| Duration of Overall Response | Duration of overall response was assessed from the time that measurement criteria were first met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease was documented. It was analyzed for responders only. Participants without observed progressive disease after an objective response were censored at the date of the last tumor assessment. | Approximately 43 Months | 
| Duration of Overall Complete Response | The duration of overall complete response was assessed from the time that measurement criteria were met for complete response until the first date that recurrent or progressive disease was objectively documented. Participants without observed progressive disease after an objective complete response were censored at the date of the last tumor assessment. | Approximately 43 Months | 
| Number of Participants With Any Adverse Events, Serious Adverse Events and Deaths | An adverse event (AEs) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. A serious adverse event is defined as any event which was fatal (resulted in death), life-threatening (with immediate risk of death), resulted in a new or prolongation of a current hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly or birth defect, considered medically significant by the investigator, required intervention to prevent one or more of the outcomes listed above. | Approximately 43 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III colon cancer, stage IV colon cancer, stage III rectal cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum