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A Phase I Study of GTI-2040 in Combination With Oxaliplatin and Capecitabine in Patients With Advanced Metastatic Solid Tumors

Phase 1
18 Years
Not Enrolling
Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IIIC Colon Cancer, Stage IIIC Rectal Cancer, Stage IVA Colon Cancer, Stage IVA Rectal Cancer, Stage IVB Colon Cancer, Stage IVB Rectal Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study of GTI-2040 in Combination With Oxaliplatin and Capecitabine in Patients With Advanced Metastatic Solid Tumors


I. To establish the maximum tolerated (MTD) of a 21 day cycle of capecitabine given orally
twice daily for 14 days in combination with oxaliplatin given intravenously on day 1 and
GTI-2040 given as a continuous infusion over 14 days in patients with advanced metastatic
solid tumors.

II. To describe the toxicities at each dose level studied.


I. To evaluate the pharmacokinetics of GTI-2040, capecitabine, and oxaliplatin when these
are given in combination.

II. To evaluate levels of ribonucleotide reductase -M2 subunit (RR-M2) mRNA levels using
TaqMan RT-PCR in peripheral blood mononuclear cells and in tumor samples (when available).
TRF support will be required and sought.

III. To quantitate changes in dCTP levels in peripheral blood mononuclear cells during
treatment as a surrogate marker of RR inhibition. TRF support will be required and sought.

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.

Inclusion Criteria:

- Patients must have locally advanced or metastatic colorectal cancer that is not
amenable to surgical treatment; selected patients with advanced disease in incurable
cancers of other types may be considered

- Patients must have histological or cytological proof of malignancy

- Patients must have had at least one standard prior chemotherapy for locally advanced
or metastatic disease with no prior oxaliplatin containing regimen; patients who
relapse within 12 months of adjuvant therapy are eligible

- Karnofsky performance status of >= 60%

- Absolute neutrophil count > 1500/ul

- Platelets > 100,000/ul

- Total bilirubin within institutional normal limits

- AST (SGOT)/ALT (SGPT) within 2.5 x institutional normal limits

- Alkaline phosphatase within 2.5x institutional normal limits

- Creatinine within institutional normal limits or a calculated creatinine clearance >
60 ml/min

- Patients should have no greater than grade 1 neuropathy (CTCAE v3.0)

- Ability to understand and the willingness to sign a written IRB approved consent

- Measurable disease not required

- Previous chemotherapy must have been completed > 21 days before treatment on this
study (> 6 weeks for mitomycin-c or nitrosoureas)

- Life expectancy of at least 12 weeks

Exclusion Criteria:

- Active or chronic hepatitis B or C

- HIV positive patients receiving antiviral therapy because of possible pharmacokinetic

- Uncontrolled intercurrent illnesses including but not limited to ongoing or active
infections, symptomatic congestive heart failure, unstable angina, or cardiac

- Pregnant or nursing women are excluded due to the potential for teratogenic effects
and for potential deleterious effects on the infant; woman of childbearing age and
men must practice an effective form of contraception

- Patients with known brain metastasis are excluded due their poor prognosis and due to
possible neurologic sequelae that could confound the evaluation of the
investigational treatment

- Patients requiring anticoagulation are excluded as polyanions are known to inhibit
clotting mechanisms and phosphorothioate oligonucleotide may act in a similar
mechanism; patients receiving low dose prophylactic Coumadin (1 mg/day) may be

- Medical, social, of psychological factors that would interfere with consent and

- Patients with a diagnosis of pulmonary fibrosis or a pulmonary interstitial process

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MTD of the combination of GTI-2040, oxaliplatin and capecitabine based on the incidence of dose-limiting toxicity (DLT) as assessed by CTCAE version 3.0

Outcome Description:

Adverse events will be summarized by grade, attribution, and organ system. Hematological and clinical chemistry laboratory results will be included in the adverse event summary.

Outcome Time Frame:

21 days

Safety Issue:


Principal Investigator

Stephen Shibata

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

May 2004

Completion Date:

Related Keywords:

  • Recurrent Colon Cancer
  • Recurrent Rectal Cancer
  • Stage IIIC Colon Cancer
  • Stage IIIC Rectal Cancer
  • Stage IVA Colon Cancer
  • Stage IVA Rectal Cancer
  • Stage IVB Colon Cancer
  • Stage IVB Rectal Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Neoplasms



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