Clinical trial NCT00087165: GTI-2040, Docetaxel, and Prednisone in Treating Patients With Prostate Cancer
Official title: A Phase II Study of GTI-2040 in Combination With Docetaxel and Prednisone in Hormone-Refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
recurrent prostate cancer
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-07-12
Enrollment: 22
Sex: MALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.
* 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.

Eligibility criteria: 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

Primary outcomes:
measure: PSA response rate
Secondary outcomes:
measure: Median survival
measure: 1-year survival
measure: Response rate and duration
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency - Vancouver Cancer Centre
state: British Columbia
city: Hamilton
country: Canada
facility: Margaret and Charles Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program at London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Regional Cancer Centre - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Princess Margaret Hospital, Canada
name: Malcolm J. Moore, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 prostate cancer. Cancer Chemother Pharmacol. 2011 Apr;67(4):927-33. doi: 10.1007/s00280-010-1389-7. Epub 2010 Jul 3.