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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00078962
First received: March 8, 2004
Last updated: January 23, 2013
Last verified: January 2013

March 8, 2004
January 23, 2013
January 2004
November 2007   (final data collection date for primary outcome measure)
  • Maximum tolerated dose (MTD) of GTI-2040 and gemcitabine hydrochloride, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v3.0 [ Time Frame: Up to day 28 ] [ Designated as safety issue: Yes ]
  • Adverse events, graded according to the NCI CTC v3.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00078962 on ClinicalTrials.gov Archive Site
  • Levels of gemcitabine triphosphate (dFdCTP) in terms of pharmacokinetics of gemcitabine hydrochloride [ Time Frame: Days 1, 2, 8, and 15 (course 1), days 1, 2, 9, and 16 (course 2) ] [ Designated as safety issue: No ]
  • Levels of ribonucleotide reductase R2 and protein expression [ Time Frame: Days 1, 2, 8, and 15 (course 1), days 1, 2, 9, and 16 (course 2) ] [ Designated as safety issue: No ]
    Student t-tests will be employed.
  • Levels of apoptotic markers and cell cycle regulatory proteins [ Time Frame: Days 1, 2, 8, and 15 (course 1), days 1, 2, 9, and 16 (course 2) ] [ Designated as safety issue: No ]
    Student t-tests will be employed.
Not Provided
Not Provided
Not Provided
 
GTI-2040 and Gemcitabine in Treating Patients With Metastatic or Unresectable Solid Tumors
A Phase I Pharmacokinetics and Pharmacodynamic Study of GTI2040 in Combination With Gemcitabine in Patients With Solid Tumors

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

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Unspecified Adult Solid Tumor, Protocol Specific
  • 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 Name: pharmacological studies
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.

Interventions:
  • Biological: GTI-2040
  • Drug: gemcitabine hydrochloride
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
40
Not Provided
November 2007   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00078962
NCI-2012-02577, 03-06, U01CA069853, CDR0000353204
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Chris Takimoto Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
National Cancer Institute (NCI)
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP