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GTI-2040 and Gemcitabine in Treating Patients With Metastatic or Unresectable Solid Tumors

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00078962
Collaborator
(none)
40
Enrollment
1
Location
1
Arm

Study Details

Study Description

Brief Summary

This phase I trial is studying the side effects and best dose of GTI-2040 and gemcitabine in treating patients with metastatic or unresectable solid tumors. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. GTI-2040 may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by making tumor cells more sensitive to gemcitabine

Condition or Disease Intervention/Treatment Phase
  • Biological: GTI-2040
  • Drug: gemcitabine hydrochloride
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
 Phase 1

Detailed Description

OBJECTIVES: Primary I. Determine the toxicity profile and maximum tolerated dose of GTI-2040 and gemcitabine in patients with metastatic or unresectable solid tumors.

Secondary I. Determine the pharmacokinetics and pharmacodynamics of this regimen in these patients.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive GTI-2040 IV continuously on days 2-16 of course 1 and on days 1-16 of all subsequent courses and gemcitabine IV over 30 minutes on days 1, 8, and 15 of course 1 and on days 2, 9, and 16 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of GTI-2040 and gemcitabine 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. Once the MTD is determined, 10 additional patients are treated at that dose.

PROJECTED ACCRUAL: Approximately 18-40 patients will be accrued for this study within 6-20 months.

Study Design

Study Type:
Interventional
Actual Enrollment :
40 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Pharmacokinetics and Pharmacodynamic Study of GTI2040 in Combination With Gemcitabine in Patients With Solid Tumors
Study Start Date :
Jan 1, 2004
Actual Primary Completion Date :
Nov 1, 2007

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (GTI-2040, gemcitabine hydrochloride)

Patients receive GTI-2040 IV continuously on days 2-16 of course 1 and on days 1-16 of all subsequent courses and gemcitabine IV over 30 minutes on days 1, 8, and 15 of course 1 and on days 2, 9, and 16 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of GTI-2040 and gemcitabine until the 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. Once the MTD is determined, 10 additional patients are treated at that dose.

Biological: GTI-2040
Given IV

Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar

    • Other: laboratory biomarker analysis
    Correlative studies

    Other: pharmacological study
    Correlative studies
    Other Names:
  • pharmacological studies

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Maximum tolerated dose (MTD) of GTI-2040 and gemcitabine hydrochloride, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v3.0 [Up to day 28]

    2. Adverse events, graded according to the NCI CTC v3.0 [Up to 2 years]

    Secondary Outcome Measures

    1. Levels of gemcitabine triphosphate (dFdCTP) in terms of pharmacokinetics of gemcitabine hydrochloride [Days 1, 2, 8, and 15 (course 1), days 1, 2, 9, and 16 (course 2)]

    2. Levels of ribonucleotide reductase R2 and protein expression [Days 1, 2, 8, and 15 (course 1), days 1, 2, 9, and 16 (course 2)]

      Student t-tests will be employed.

    3. Levels of apoptotic markers and cell cycle regulatory proteins [Days 1, 2, 8, and 15 (course 1), days 1, 2, 9, and 16 (course 2)]

      Student t-tests will be employed.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Histologically or cytologically confirmed solid tumor

    • Metastatic or unresectable disease for which standard curative or palliative measures do not exist or are no longer effective

    • Measurable or evaluable disease

    • No known active or progressive brain metastases or primary brain tumors

    • Performance status - ECOG 0-2

    • Performance status - Karnofsky 60-100%

    • More than 12 weeks

    • Hemoglobin > 9 g/dL

    • Absolute neutrophil count ≥ 1,500/mm^3

    • Platelet count ≥ 100,000/mm^3

    • Bilirubin ≤ 2 times upper limit of normal (ULN)

    • AST and ALT ≤ 3 times ULN (5 times ULN if hepatic metastases are present)

    • Creatinine ≤ 2.0 mg/dL

    • Creatinine clearance ≥ 50 mL/min

    • No symptomatic congestive heart failure

    • No unstable angina pectoris

    • No cardiac arrhythmia

    • Not pregnant or nursing

    • Negative pregnancy test

    • Fertile patients must use effective contraception

    • No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs

    • No ongoing or active infection

    • No psychiatric illness or social situation that would preclude study compliance

    • No other condition (e.g., dementia or developmental delay) that would preclude giving informed consent

    • No other concurrent uncontrolled illness that would preclude study participation

    • Prior biologic therapy allowed

    • No concurrent biologic therapy

    • No concurrent immunotherapy

    • No concurrent routine filgrastim (G-CSF) or sargramostim (GM-CSF)

    • Prior gemcitabine allowed

    • Prior investigational chemotherapy allowed

    • At least 4 weeks since prior chemotherapy (6 weeks for mitomycin, carmustine, or nitrosoureas) and recovered

    • No other concurrent chemotherapy

    • Concurrent hormonal therapy (e.g., luteinizing hormone-releasing hormone agonists) for prostate cancer is allowed

    • At least 4 weeks since prior radiotherapy and recovered

    • No prior radiotherapy to more than 25% of bone marrow

    • No concurrent radiotherapy

    • Recovered from prior surgery

    • No other concurrent investigational therapy

    • No other concurrent anticancer therapy

    • No concurrent combination antiretroviral therapy for HIV-positive patients

    • No concurrent long-term oral anticoagulation therapy (e.g., warfarin)

    • Prophylactic warfarin to maintain central venous access patency allowed

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Cancer Therapy and Research Center at The UT Health Science Center at San Antonio San Antonio Texas United States 78229

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Chris Takimoto, Cancer Therapy and Research Center at The UT Health Science Center at San Antonio

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00078962
    Other Study ID Numbers:
    • NCI-2012-02577
    • 03-06
    • U01CA069853
    • CDR0000353204
    First Posted:
    Mar 9, 2004
    Last Update Posted:
    Jan 24, 2013
    Last Verified:
    Jan 1, 2013
    Additional relevant MeSH terms:
    Neoplasms
    Gemcitabine

    Study Results

    No Results Posted as of Jan 24, 2013