GTI-2040, Oxaliplatin, and Capecitabine in Treating Patients With Locally Advanced or Metastatic Colorectal Cancer or Other Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00084643
First received: June 10, 2004
Last updated: March 26, 2013
Last verified: January 2013
  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. 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


Condition Intervention Phase
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
Biological: GTI-2040
Drug: oxaliplatin
Drug: capecitabine
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of GTI-2040 in Combination With Oxaliplatin and Capecitabine in Patients With Advanced Metastatic Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Objective response (confirmed PR and CR) according to RECIST [ Time Frame: At 6 weeks ] [ Designated as safety issue: No ]
    Calculated with exact binomial 95% confidence interval.

  • Pharmacokinetics [ Time Frame: At baseline, and at 7 and 14 days after the start of infusion ] [ Designated as safety issue: No ]
    Peak and integrated blood levels will be summarized by dose level, and displayed in scatterplots with RR-M2 mRNA levels and changes.

  • Change in biochemical and molecular correlates [ Time Frame: From baseline to up to 4 years ] [ Designated as safety issue: No ]
    Molecular correlates will be analyzed descriptively in relation to clinical outcome. The association with progression-free survival or overall survival will be assessed by dichotomizing the measures of gene expression at the median (or by previously-established cut-points) and constructing Kaplan-Meier plots.


Enrollment: 20
Study Start Date: May 2004
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (GTI-2040, capecitabine, oxaliplatin)
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.
Biological: GTI-2040
Given IV
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: capecitabine
Given orally
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 document
  • 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 interactions
  • Uncontrolled intercurrent illnesses including but not limited to ongoing or active infections, symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia
  • 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 included
  • Medical, social, of psychological factors that would interfere with consent and follow-up
  • Patients with a diagnosis of pulmonary fibrosis or a pulmonary interstitial process
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00084643

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
Investigators
Principal Investigator: Stephen Shibata Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00084643     History of Changes
Other Study ID Numbers: NCI-2012-03077, PHI-41, U01CA062505, CDR0000365466
Study First Received: June 10, 2004
Last Updated: March 26, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Rectal Neoplasms
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Capecitabine
Fluorouracil
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014