Bicalutamide With or Without Enzastaurin in Treating Patients With Prostate Cancer

NCT00685633 | Withdrawn Phase 2

• 2 other identifiers: CDR0000596077ECOG-E1807
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

RATIONALE: Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, may lessen the amount of androgens made by the body. Enzastaurin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving bicalutamide together with enzastaurin is more effective than bicalutamide alone in treating prostate cancer. PURPOSE: This randomized phase II trial is studying bicalutamide to see how well it works compared with giving bicalutamide together with enzastaurin in treating patients with prostate cancer.

Conditions

Prostate Cancer

Keywords

stage I prostate cancer; stage II prostate cancer; stage III prostate cancer; recurrent prostate cancer

Outcome Measures

Primary Outcomes (1)

• Comparison of proportion of patients with undetectable prostate-specific antigen PSA level (< 0.2 ng/mL) at 44 weeks

Secondary Outcomes (7)

• Comparison of proportion of patients achieving ≥ 85% PSA decline at 44 weeks

• PSA response

• Time to PSA progression

• Time to PSA nadir

• Duration of PSA response

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Patients are observed without treatment in weeks 1-12. Patients with a prostate-specific antigen (PSA) rise of \> 50% above baseline or nadir (whichever is lowest) and a rise of at least 5 ng/mL, confirmed by a repeat PSA at least 2 weeks later, may be started on bicalutamide before the end of week 12 at the discretion of the treating physician. In weeks 13-44, patients with a rise PSA ≥ 50% above baseline or nadir, and a PSA rise of at least 5 ng/mL confirmed by a repeat PSA at least 2 weeks later, are removed from study. Patients receive oral bicalutamide once daily. Patients achieving a PSA decline ≥ 50% in the absence of toxicity may continue to receive bicalutamide up to 72 weeks.

Drug: bicalutamide

Arm B

ACTIVE COMPARATOR

In weeks 1-12, patients receive oral enzastaurin hydrochloride twice daily. Patients with a PSA rise of \> 50% above baseline or nadir, and a rise of at least 5 ng/mL, confirmed by a repeat PSA at least 2 weeks later, may be started on bicalutamide before the end of week 12 at the discretion of the treating physician. In weeks 13-44, patients with a PSA rise of ≥ 50% above baseline or nadir, and a rise of at least 5 ng/mL, confirmed by a repeat PSA at least 2 weeks later, are removed from study. Patients receive oral enzastaurin twice daily and oral bicalutamide once daily. Patients achieving a PSA decline ≥ 50% in the absence of toxicity may continue on this combination therapy up to 72 weeks.

Drug: bicalutamide; Drug: enzastaurin hydrochloride

Interventions

bicalutamide DRUG

Given orally

Arm A; Arm B

enzastaurin hydrochloride DRUG

Given orally

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed prostate cancer * Hormone-sensitive disease, as evidenced by a serum total testosterone level \> 150 ng/dL * No evidence of metastatic disease on physical exam, CT abdomen/pelvis (or MRI), chest x-ray or CT scan and bone scan within 6 weeks prior to randomization * Underwent prior definitive surgery or radiotherapy * Must have evidence of biochemical failure after primary therapy and subsequent progression as determined by 1 of the following: * Prostate-specific antigen (PSA) ≥ 0.4 ng/mL (in case of radical prostatectomy) * PSA rise ≥ 2 ng/mL above the nadir PSA (in case of radiotherapy) * Baseline PSA must be at least 2 ng/mL and no greater than 50 ng/mL * PSA doubling time (PSADT) \< 12 months PATIENT CHARACTERISTICS: * ECOG performance status 0 - 1 * Granulocytes ≥ 1,500/mm\^3 * Platelet count ≥ 75,000/mm\^3 * Serum creatinine normal or creatinine clearance ≥ 60 mL/min * Serum total bilirubin ≤ 1.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 2.5 times ULN * SGOT and SGPT \< 2.5 times ULN * PT/INR normal * Fertile patients must use effective barrier contraception during and for at least 3 months after completion of study treatment * No gastrointestinal (GI) tract disease resulting in: inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, or uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis) * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to enzastaurin hydrochloride or bicalutamide * No uncontrolled intercurrent illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness/social situations that would limit compliance with study requirements * A history of other malignancy is permitted if the patient is predicted to be disease-free for 2 years PRIOR CONCURRENT THERAPY: * See Disease Characteristics * More than 4 weeks since prior salvage therapy with intent to cure (i.e., surgery, radiotherapy, or other local ablative procedures) * More than 4 weeks since prior prophylactic radiotherapy to prevent gynecomastia * More than 1 year since prior therapy modulating testosterone levels (such as luteinizing-hormone releasing-hormone agonists/antagonists and antiandrogens) unless in the neoadjuvant or adjuvant setting * No 5 alpha reductase inhibitors, ketoconazole, megestrol acetate, systemic steroids, or herbal supplements during PSA value collection * At least 14 days since prior enzyme-inducing anti-epileptic drugs (EIAEDs) * Patients who must begin EIAED therapy while on study are allowed to remain * No concurrent combination antiretroviral therapy for HIV-positive patients * No concurrent anticoagulant therapy * Low dosage acetyl salicylic acid ≤ 325 mg/day allowed * No other concurrent investigational agents or anticancer therapy (i.e., chemotherapy, immunotherapy, radiotherapy, surgery for cancer, or experimental medications) * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to enzastaurin or bicalutamide * Prior neoadjuvant and/or adjuvant therapy ≤ 4 weeks prior to randomization (i.e., hormones, chemotherapy, vaccines, or experimental agents) allowed if PSA rise and PSADT were documented after testosterone level was \> 150 ng/dL

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Eastern Cooperative Oncology Group: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

bicalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Anna C. Ferrari, MD

  NYU Langone Health

  STUDY CHAIR

• Ronald Rodriguez, MD, PhD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: May 24, 2008
• First Posted: May 28, 2008
• Study Start: December 1, 2008
• Primary Completion: June 1, 2010
• Last Updated: August 20, 2013

Record last verified: 2008-11