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CWRU 1296: Biochemical and Pharmacokinetic Predictors of Colon Cancer Response to a Topoisomerase I Directed Treatment With Irinotecan


Phase 2
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer

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Trial Information

CWRU 1296: Biochemical and Pharmacokinetic Predictors of Colon Cancer Response to a Topoisomerase I Directed Treatment With Irinotecan


OBJECTIVES: I. Confirm the greater than 20% response rate to irinotecan in patients with
metastatic or recurrent colorectal cancer who have not receive prior chemotherapy for their
advanced disease. II. Characterize pharmacokinetic parameters of irinotecan and its
metabolite SN-38 and their relationship to response and toxic effect. III. Characterize
tumor samples for topoisomerase I activity, proliferative fraction (ki67 expression), and
p53 expression and determine whether clinical response is related to these tumor
characteristics in patient population. IV. Determine the in vitro inhibition of
topoisomerase I activity by irinotecan, SN-38, and other camptothecin analogs and evaluate
whether the degree of in vitro sensitivity to irinotecan and/or SN-38 is associated with
clinical response in these patients. VII. Determine the frequency of somatic mutations
following irinotecan and correlate this with pharmacologic parameters.

OUTLINE: Patients receive irinotecan IV at a starting dose weekly for 4 weeks followed by 2
weeks of rest. Treatment continues in the absence of disease progression or unacceptable
toxicity. Tumor status is reassessed every 12 weeks during study. Patients attaining a
complete response may receive additional courses of treatment. Patients are followed until
death.

PROJECTED ACCRUAL: A total of 54 patients will be accrued into this study at a rate of 25
patients per year.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically confirmed metastatic or recurrent adenocarcinoma
of the colon or rectum that is incurable by surgery or radiation therapy A metastatic
lesion in the liver or lung should be evaluated for definitive surgical treatment before
being considered for this study Measurable disease required Elevated CEA, hepatomegaly
ascites, pleural effusion, positive nuclear scan or bone scan, or poorly defined pelvic or
abdominal mass are NOT considered measurable disease Must have measurable disease outside
the radiation port or progression of disease within a previously radiated area Must be
eligible for a biopsy of a malignant lesion No ascites that are detectable on physical
exam No brain metastasis

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy:
Greater than 12 weeks Hematopoietic: WBC at least 4,000/mm3 Granulocyte count at least
1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.2 mg/dL
SGOT less than 4 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL
or Creatinine clearance at least 60 mL/min Other: No history of any other malignancy
except curatively treated nonmelanoma skin cancer and carcinoma in situ of the cervix No
active infection or other serious medical conditions deemed unacceptable Negative
pregnancy test Effective contraception required of all fertile patients

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior
chemotherapy for advanced disease Endocrine therapy: Not specified Radiotherapy: See
Disease Characteristics At least 3 weeks since prior radiotherapy Surgery: At least 3
weeks since any surgical procedure

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Effectiveness of irinotecan in treating patients who have metastatic or recurrent colorectal cancer.

Outcome Time Frame:

Starting dose weekly for 4 weeks followed by 2 weeks of rest. Treatment continues in the absence of disease progression or unacceptable toxicity. Tumor status is reassessed every 12 weeks during study.

Safety Issue:

No

Principal Investigator

James KV Willson, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CWRU1296

NCT ID:

NCT00002933

Start Date:

September 1996

Completion Date:

January 2001

Related Keywords:

  • Colorectal Cancer
  • stage IV colon cancer
  • stage IV rectal cancer
  • recurrent colon cancer
  • recurrent rectal cancer
  • adenocarcinoma of the colon
  • adenocarcinoma of the rectum
  • Colonic Neoplasms
  • Colorectal Neoplasms

Name

Location

Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
Veterans Affairs Medical Center - ClevelandCleveland, Ohio  44106