GTI-2040, Docetaxel, and Prednisone in Treating Patients With Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

A Phase II Study of GTI-2040 in Combination With Docetaxel and Prednisone in Hormone-Refractory Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00087165
• Other study ID #: PMH-PHL-024
• Secondary ID: CDR0000372951NCI
• Status: Completed
• Phase: Phase 2
• Start date: January 2005
• Est. completion date: December 2006

Study information

• Verified date: April 2021
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

• Determine the median time to progression in patients treated with this regimen.

• Determine the safety and tolerability of this regimen in these patients.

• Determine the median duration of PSA response in patients treated with this regimen.

• 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: December 2006
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

• Histologically or cytologically confirmed adenocarcinoma of the prostate

• Metastatic carcinoma of presumptive prostate origin

• Bony metastases AND a serum prostate-specific antigen (PSA) level > 20 ng/mL

• Disease progression after prior hormonal therapy as defined by rising PSA levels

• At least 2 consecutive rises in PSA over a reference value, with measurements taken at least 7 days apart

• Prior hormonal therapy must include either medical (luteinizing hormone-releasing hormone [LHRH] agonist) OR surgical (orchiectomy) castration

• Patients who received prior LHRH agonist must continue or re-start such therapy

• Castrate levels of testosterone < 50 ng/dL

• PSA = 20 ng/mL

• 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)

• Bilirubin normal

• 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

• No cardiac arrhythmia

Other

• Fertile patients must use effective contraception

• No symptomatic peripheral neuropathy = grade 2

• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to GTI-2040 or other study agents

• No concurrent uncontrolled illness

• No active or ongoing infection

• 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

• At least 4 weeks since prior estramustine and recovered

Endocrine therapy

• See Disease Characteristics

• At least 6 weeks since prior bicalutamide*

• At least 4 weeks since prior flutamide, nilutamide, or cyproterone*

• Concurrent steroids allowed NOTE: *Patients must have evidence of disease progression despite cessation of antiandrogen therapy

Radiotherapy

• At least 4 weeks since prior radiotherapy

• No prior radiotherapy to > 25% of bone marrow

• No prior isotope therapy

Surgery

• See Disease Characteristics

Other

• No concurrent prophylactic antibiotics

• No concurrent anticoagulants

• Concurrent low-dose warfarin for prophylaxis of central line thrombosis allowed

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No other concurrent investigational agents or therapies

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Biological:
• GTI-2040

Drug:
• docetaxel

• prednisone

Locations

Country	Name	City	State
Canada	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Regional Cancer Program at London Health Sciences Centre	London	Ontario
Canada	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	British Columbia Cancer Agency - Vancouver Cancer Centre	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	National Cancer Institute (NCI)

Country where clinical trial is conducted

Canada, 

References & Publications (1)

Sridhar SS, Canil CM, Chi KN, Hotte SJ, Ernst S, Wang L, Chen EX, Juhasz A, Yen Y, Murray P, Zwiebel JA, Moore MJ. A phase II study of the antisense oligonucleotide GTI-2040 plus docetaxel and prednisone as first-line treatment in castration-resistant pro — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PSA response rate
Secondary	Median survival
Secondary	1-year survival
Secondary	Response rate and duration