GTI-2040, Docetaxel, and Prednisone in Treating Patients With Prostate Cancer
Study Details
Study Description
Brief Summary
RATIONALE: GTI-2040 may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. GTI-2040 may help docetaxel kill more tumor cells by making them more sensitive to the drug.
PURPOSE: This phase II trial is studying how well giving GTI-2040 together with docetaxel and prednisone works in treating patients with prostate cancer that has not responded to hormone therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
OBJECTIVES:
Primary
- Determine the efficacy of GTI-2040, docetaxel, and prednisone, in terms of prostate-specific antigen (PSA) response rate, in patients with hormone-refractory prostate cancer.
Secondary
-
Determine objective tumor response in patients treated with this regimen.
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Determine the median time to progression in patients treated with this regimen.
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Determine the safety and tolerability of this regimen in these patients.
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Determine the median duration of PSA response in patients treated with this regimen.
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Correlate baseline and post-treatment levels of ribonucleotide reductase activity in tumor biopsies and peripheral blood mononuclear cells and tumoral expression of c-myc, R2 subunit protein, and markers of cellular proliferation and apoptosis with clinical outcomes in patients treated with this regimen.
OUTLINE: This is an open-label, multicenter study.
Patients receive GTI-2040 IV continuously on days 1-14, docetaxel IV on day 3 of course 1 and on day 1 of subsequent courses, and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 18-46 patients will be accrued for this study within 3.6-9.5 months.
Study Design
Outcome Measures
Primary Outcome Measures
- PSA response rate []
Secondary Outcome Measures
- Median survival []
- 1-year survival []
- Response rate and duration []
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
-
Diagnosis of 1 of the following:
-
Histologically or cytologically confirmed adenocarcinoma of the prostate
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Metastatic carcinoma of presumptive prostate origin
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Bony metastases AND a serum prostate-specific antigen (PSA) level > 20 ng/mL
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Disease progression after prior hormonal therapy as defined by rising PSA levels
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At least 2 consecutive rises in PSA over a reference value, with measurements taken at least 7 days apart
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Prior hormonal therapy must include either medical (luteinizing hormone-releasing hormone [LHRH] agonist) OR surgical (orchiectomy) castration
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Patients who received prior LHRH agonist must continue or re-start such therapy
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Castrate levels of testosterone < 50 ng/dL
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PSA ≥ 20 ng/mL
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No known brain metastases
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
-
ECOG 0-2 OR
-
Karnofsky 60-100%
Life expectancy
- More than 3 months
Hematopoietic
-
Absolute neutrophil count ≥ 1,500/mm^3
-
Platelet count ≥ 100,000/mm^3
-
WBC ≥ 3,000/mm^3
Hepatic
-
AST and ALT ≤ 1.5 times upper limit of normal (ULN)
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Bilirubin normal
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PTT ≤ 1.25 times upper limit of control
-
INR ≤ 1.3
Renal
-
Creatinine ≤ 1.5 times ULN OR
-
Creatinine clearance ≥ 50 mL/min
Cardiovascular
-
No symptomatic congestive heart failure
-
No unstable angina pectoris
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No cardiac arrhythmia
Other
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Fertile patients must use effective contraception
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No symptomatic peripheral neuropathy ≥ grade 2
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No history of allergic reaction attributed to compounds of similar chemical or biologic composition to GTI-2040 or other study agents
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No concurrent uncontrolled illness
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No active or ongoing infection
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No psychiatric illness or social situation that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent prophylactic filgrastim (G-CSF) or epoetin alfa
Chemotherapy
-
No prior chemotherapy except monotherapy with oral estramustine
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At least 4 weeks since prior estramustine and recovered
Endocrine therapy
-
See Disease Characteristics
-
At least 6 weeks since prior bicalutamide*
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At least 4 weeks since prior flutamide, nilutamide, or cyproterone*
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Concurrent steroids allowed NOTE: *Patients must have evidence of disease progression despite cessation of antiandrogen therapy
Radiotherapy
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At least 4 weeks since prior radiotherapy
-
No prior radiotherapy to > 25% of bone marrow
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No prior isotope therapy
Surgery
- See Disease Characteristics
Other
-
No concurrent prophylactic antibiotics
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No concurrent anticoagulants
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Concurrent low-dose warfarin for prophylaxis of central line thrombosis allowed
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No concurrent combination antiretroviral therapy for HIV-positive patients
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No other concurrent investigational agents or therapies
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | British Columbia Cancer Agency - Vancouver Cancer Centre | Vancouver | British Columbia | Canada | V5Z 4E6 |
| 2 | Margaret and Charles Juravinski Cancer Centre | Hamilton | Ontario | Canada | L8V 5C2 |
| 3 | London Regional Cancer Program at London Health Sciences Centre | London | Ontario | Canada | N6A 4L6 |
| 4 | Ottawa Hospital Regional Cancer Centre - General Campus | Ottawa | Ontario | Canada | K1H 8L6 |
| 5 | Princess Margaret Hospital | Toronto | Ontario | Canada | M5G 2M9 |
Sponsors and Collaborators
- University Health Network, Toronto
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Malcolm J. Moore, MD, Princess Margaret Hospital, Canada
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PMH-PHL-024
- CDR0000372951
- NCI-6102