Tocladesine in Treating Patients With Recurrent or Progressive Metastatic Colorectal Cancer

Phase I Study Of Tocladesine In Patients With Colorectal Carcinoma Following Therapy With 5-FU And Irinotecan

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the effectiveness of tocladesine in treating patients who have recurrent or progressive metastatic colorectal cancer.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: tocladesine

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of tocladesine in patients with recurrent or progressive metastatic colorectal cancer.
• Determine the qualitative and quantitative toxicity of this drug in these patients.
• Assess any therapeutic activity in patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive tocladesine IV continuously on days 1-5 and 8-12. Treatment repeats every 21 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tocladesine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 14 additional patients are treated at this dose level.

PROJECTED ACCRUAL: A total of 3-38 patients will be accrued for this study.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center, UCLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of metastatic carcinoma of the colon or rectum

  • Recurrent or progressive after failing prior fluorouracil and irinotecan chemotherapy, sequentially or in combination, unless unable to tolerate irinotecan
• Measurable disease

PATIENT CHARACTERISTICS:

Age:

• 18 to 75

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 5 times ULN
• PT/aPTT no greater than 1.2 times ULN

Renal:

• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 50 mL/min
• No impaired renal function

Cardiovascular:

• No impaired cardiac function

Other:

• No active infection
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• Not specified

Other:

• No other concurrent anticancer drugs
• No concurrent chronic non-steroidal anti-inflammatory agents
• No concurrent chronic therapeutic anticoagulation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: April 1, 2001

Study Registration Dates

• First Submitted: July 11, 2001
• First Submitted That Met QC Criteria: September 9, 2003
• First Posted (Estimate): September 10, 2003

Study Record Updates

• Last Update Posted (Estimate): August 2, 2013
• Last Update Submitted That Met QC Criteria: August 1, 2013
• Last Verified: October 1, 2002

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; 8-chloro-cyclic adenosine monophosphate
• Other Study ID Numbers: ICN-2000-1; UCLA-0006008; CDR0000068764 (Registry Identifier: PDQ (Physician Data Query)); NCI-G01-1979