Back to resultsCapecitabine and Irinotecan in Treating Patients With Locally Advanced, Recurrent, or Metastatic Colorectal Cancer
Primary Purpose
Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Capecitabine
Irinotecan
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring 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
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
Sites / Locations
- University of Alabama at Birmingham Comprehensive Cancer Center
- Loma Linda University Cancer Institute at Loma Linda University Medical Center
- Eastern Connecticut Hematology and Oncology Associates
- Lombardi Cancer Center at Georgetown University Medical Center
- George Washington University Medical Center
- University of Florida Health Science Center - Jacksonville
- Markey Cancer Center at University of Kentucky Chandler Medical Center
- St. Louis University Hospital Cancer Center
- Lincoln Medical and Mental Health Center
- HemOnCare, P.C.
- Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
- Fox Chase Cancer Center
- Charleston Hematology-Oncology, P.A.
- Cancer Center at the University of Virginia
- Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
- Rockwood Clinic P.S.
- West Virginia University Hospitals
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1,Initial Regimen:(Capecitabine + Irinotecan )
Cohort 2,Amended Regimen:(Capecitabine + Irinotecan)
Arm 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).
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).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00022698
Brief Title
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
2. Study Status
Record Verification Date
February 2005
Overall Recruitment Status
Completed
Study Start Date
May 2001 (undefined)
Primary Completion Date
December 2004 (Actual)
Study Completion Date
December 2004 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
67 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1,Initial Regimen:(Capecitabine + Irinotecan )
Arm Type
Experimental
Arm 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).
Arm Title
Cohort 2,Amended Regimen:(Capecitabine + Irinotecan)
Arm Type
Experimental
Arm 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).
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Primary Outcome Measure Information:
Title
Tumor Response Rate Based on Tumor Measurement as Per Response Evaluation Criteria In Solid Tumors Version 1.0 (RECIST 1.0)
Description
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.
Time Frame
Approximately 43 Months
Secondary Outcome Measure Information:
Title
Time to Disease Progression
Description
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.
Time Frame
Approximately 43 Months
Title
Time to Treatment Failure
Description
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.
Time Frame
Approximately 43 Months
Title
Percentage of Participants With One-year Survival
Description
Survival was measured as the time from start of treatment to the date of death or till one year whichever occurred first.
Time Frame
Up to Month 12
Title
Overall Survival
Description
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.
Time Frame
Approximately 43 Months
Title
Time To Objective Response
Description
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.
Time Frame
Approximately 43 Months
Title
Duration of Overall Response
Description
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.
Time Frame
Approximately 43 Months
Title
Duration of Overall Complete Response
Description
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.
Time Frame
Approximately 43 Months
Title
Number of Participants With Any Adverse Events, Serious Adverse Events and Deaths
Description
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.
Time Frame
Approximately 43 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham Comprehensive Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-3300
Country
United States
Facility Name
Loma Linda University Cancer Institute at Loma Linda University Medical Center
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
Eastern Connecticut Hematology and Oncology Associates
City
Norwich
State/Province
Connecticut
ZIP/Postal Code
06360
Country
United States
Facility Name
Lombardi Cancer Center at Georgetown University Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
George Washington University Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
University of Florida Health Science Center - Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
Markey Cancer Center at University of Kentucky Chandler Medical Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536-0084
Country
United States
Facility Name
St. Louis University Hospital Cancer Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110-0250
Country
United States
Facility Name
Lincoln Medical and Mental Health Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10451
Country
United States
Facility Name
HemOnCare, P.C.
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11235
Country
United States
Facility Name
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107-5541
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Charleston Hematology-Oncology, P.A.
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29403
Country
United States
Facility Name
Cancer Center at the University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Rockwood Clinic P.S.
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States
Facility Name
West Virginia University Hospitals
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506-9300
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
16943524
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.
Results Reference
result
PubMed Identifier
15709193
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.
Results Reference
result
Learn more about this trial
Capecitabine and Irinotecan in Treating Patients With Locally Advanced, Recurrent, or Metastatic Colorectal Cancer
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