RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. GTI-2040 may increase the effectiveness of chemotherapy by making tumor cells more sensitive to the drugs. Giving GTI-2040 together with oxaliplatin and capecitabine may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of capecitabine when given together with GTI-2040 and oxaliplatin in treating patients with locally advanced or metastatic colorectal cancer or other solid tumors.

Condition	Treatment or Intervention	Phase
adult solid tumor Colon Cancer Rectal Cancer	Drug: GTI-2040  Drug: capecitabine  Drug: oxaliplatin  Procedure: antisense therapy  Procedure: chemosensitization/potentiation  Procedure: chemotherapy	Phase I

Further Study Details: 

OBJECTIVES: Primary

• Determine the maximum tolerated dose of capecitabine when administered with oxaliplatin and GTI-2040 in patients with locally advanced or metastatic colorectal cancer or other solid tumors.
• Determine the toxic effects of this regimen in these patients.

Secondary

• Determine the pharmacokinetics of this regimen in these patients.

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

Patients receive GTI-2040 IV continuously on days 1-14, oral capecitabine twice daily on days 2-15, and oxaliplatin IV over 2 hours on day 2 of the first course. In all subsequent courses, capecitabine is administered on days 1-14, oxaliplatin is administered on day 1, and GTI-2040 is administered as in course 1. Courses repeat every 21 days in the absence of disease progression and unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 15-20 patients will be accrued for this study within 1 year.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed colorectal cancer not amenable to surgical therapy
• Locally advanced or metastatic disease
• Other advanced incurable selected solid tumors allowed
• Received at least 1 prior standard chemotherapy regimen for locally advanced or metastatic disease
• No prior oxaliplatin-containing regimen
• Relapsed disease within 12 months of adjuvant therapy allowed
• No known brain metastasis

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count > 1,500/mm^3
• Platelet count > 100,000/mm^3

Hepatic

• AST and ALT ≤ 2.5 times normal
• Alkaline phosphatase ≤ 2.5 times normal
• Bilirubin normal
• No active or chronic hepatitis B or C

Renal

• Creatinine normal OR
• Creatinine clearance > 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina
• No cardiac arrhythmia

Pulmonary

• No pulmonary fibrosis
• No pulmonary interstitial process

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No neuropathy > grade 1
• No concurrent uncontrolled illness
• No active or ongoing infection
• No medical, social, or psychological factors that would preclude study compliance and giving informed consent

PRIOR CONCURRENT THERAPY: Biologic therapy

• No concurrent colony-stimulating factors during the first course of study treatment

Chemotherapy

• See Disease Characteristics
• More than 21 days since prior chemotherapy (6 weeks for mitomycin or nitrosoureas)

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No concurrent anticoagulation therapy
• Low-dose prophylactic warfarin (1 mg/day) allowed
• No concurrent antiviral therapy for HIV-positive patients

California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      City of Hope Medical Group, Pasadena,  California,  91105,  United States; Recruiting
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033,  United States; Recruiting

Study ID Numbers:  CDR0000365466; CCC-PHI-41; CHNMC-PHI-41; NCI-6099; NCT00084643
Record last reviewed:  September 2004
Last Updated:  April 5, 2005
Record first received:  June 10, 2004
ClinicalTrials.gov Identifier:  NCT00084643
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08