Clinical trial NCT00022698: Capecitabine and Irinotecan in Treating Patients With Locally Advanced, Recurrent, or Metastatic Colorectal Cancer
Official title: A Phase II Study of Oral Xeloda (Capecitabine) in Combination With Intravenous Irinotecan for Patients With Locally Advanced and/or Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: 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
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2003-01-27
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: Tumor Response Rate Based on Tumor Measurement as Per Response Evaluation Criteria In Solid Tumors Version 1.0 (RECIST 1.0)
timeFrame: Approximately 43 Months
Secondary outcomes:
measure: Time to Disease Progression
timeFrame: Approximately 43 Months
measure: Time to Treatment Failure
timeFrame: Approximately 43 Months
measure: Percentage of Participants With One-year Survival
timeFrame: Up to Month 12
measure: Overall Survival
timeFrame: Approximately 43 Months
measure: Time To Objective Response
timeFrame: Approximately 43 Months
measure: Duration of Overall Response
timeFrame: Approximately 43 Months
measure: Duration of Overall Complete Response
timeFrame: Approximately 43 Months
measure: Number of Participants With Any Adverse Events, Serious Adverse Events and Deaths
timeFrame: Approximately 43 Months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Loma Linda
country: United States
facility: Loma Linda University Cancer Institute at Loma Linda University Medical Center
state: California
city: Norwich
country: United States
facility: Eastern Connecticut Hematology and Oncology Associates
state: Connecticut
city: Washington
country: United States
facility: Lombardi Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Washington
country: United States
facility: George Washington University Medical Center
state: District of Columbia
city: Jacksonville
country: United States
facility: University of Florida Health Science Center - Jacksonville
state: Florida
city: Lexington
country: United States
facility: Markey Cancer Center at University of Kentucky Chandler Medical Center
state: Kentucky
city: Saint Louis
country: United States
facility: St. Louis University Hospital Cancer Center
state: Missouri
city: Bronx
country: United States
facility: Lincoln Medical and Mental Health Center
state: New York
city: Brooklyn
country: United States
facility: HemOnCare, P.C.
state: New York
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology-Oncology, P.A.
state: South Carolina
city: Charlottesville
country: United States
facility: Cancer Center at the University of Virginia
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Spokane
country: United States
facility: Rockwood Clinic P.S.
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Hospitals
state: West Virginia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Meropol NJ, Gold PJ, Diasio RB, Andria M, Dhami M, Godfrey T, Kovatich AJ, Lund KA, Mitchell E, Schwarting R. Thymidine phosphorylase expression is associated with response to capecitabine plus irinotecan in patients with metastatic colorectal cancer. J Clin Oncol. 2006 Sep 1;24(25):4069-77. doi: 10.1200/JCO.2005.05.2084.
citation: Carlini LE, Meropol NJ, Bever J, Andria ML, Hill T, Gold P, Rogatko A, Wang H, Blanchard RL. UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res. 2005 Feb 1;11(3):1226-36.