Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	CTRC-IDD-0306 NCI-6090, NCT00078962, 6090

Objectives

Primary

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

Secondary

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

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• Prior biologic therapy allowed
• No concurrent biologic therapy
• No concurrent immunotherapy
• No concurrent routine filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

• 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

Endocrine therapy

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

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered
• No prior radiotherapy to more than 25% of bone marrow
• No concurrent radiotherapy

Surgery

• Recovered from prior surgery

Other

• 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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• Hemoglobin > 9 g/dL
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN (5 times ULN if hepatic metastases are present)

Renal

• Creatinine ≤ 2.0 mg/dL

  OR

• Creatinine clearance ≥ 50 mL/min

Cardiovascular

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

Other

• 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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Institute for Drug Development

Chris Takimoto, MD, PhD, FACP, Protocol chair		Ph: 210-562-1725; 800-340-2872

Registry Information
Official Title		A Phase I Pharmacokinetics and Pharmacodynamic Study of GTI2040 in Combination with Gemcitabine in Patients with Solid Tumors
Trial Start Date		2004-01-12
Registered in ClinicalTrials.gov		NCT00078962
Date Submitted to PDQ		2004-01-14
Information Last Verified		2006-11-05
NCI Grant/Contract Number		CA69853

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