A Pilot Study of Parenteral Testosterone and Oral Etoposide as Therapy for Men With Castration Resistant Prostate Cancer

Summary

The objective of the study is to determine if men with evidence of progressive prostate cancer while on chronic androgen ablation of ≥ 1 year duration will exhibit a clinical response following administration of parenteral testosterone and oral etoposide.

Treatment Plan: Eligible patients will continue on androgen ablative therapy with luteinizing hormone-releasing hormone (LHRH) agonist (i.e. Zoladex or Lupron) if not surgically castrated. Patients will receive intramuscular injection with testosterone cypionate at a dose of 400 mg every month for a total of 3 injections (i.e. 3 months of therapy). This dose was selected based on data demonstrating that it produces an initial supraphysiologic serum level of testosterone (i.e. \> 3-5 times normal level) with eugonadal levels achieved at the end of two weeks. Beginning the day of the testosterone injection, patients will also receive oral etoposide 100 mg/day in divided doses (50 mg q 12h) x 14 days out of 28 days per cycle. After 3 months on therapy, patients will have repeat prostate specific antigen (PSA) and bone/computed tomography (CT) scans to establish the effect of combined testosterone and etoposide treatment on these parameters (i.e. "testosterone effect baseline"). Patients with sustained elevations in PSA ≥ 50% above pre-testosterone treatment PSA levels after the initial three months of testosterone and etoposide therapy will not receive continued therapy and will come off study. Patients with PSA levels less than the peak serum PSA level seen over the three month period (PSA decline) or patients with PSA ≤ 50% of pretreatment baseline will receive a second 3 month course of monthly testosterone and etoposide therapy until evidence of disease progression. Disease progression is defined as a PSA increase above the PSA level obtained after 3 months on testosterone treatment over two successive measurements 2 weeks apart or evidence of new lesions or progression on bone/CT scans compared to baseline studies. Patients who respond to initial treatment with testosterone and etoposide and then show signs of progression will have the option of retreatment with testosterone alone after a period of 3 months or greater off of the original therapy.

Conditions

• Prostate Cancer

Interventions

DRUG

Testosterone injection

Patients will receive an intramuscular gluteal injection with testosterone cypionate at a dose of 400 mg every month for a total of 3 injections (i.e. 3 months of therapy). This route and dose of testosterone was selected based on data demonstrating that it produces an initial supraphysiologic serum level of testosterone (i.e. \> 3-5 times normal level) with eugonadal levels achieved at the end of two weeks.

DRUG

Etoposide

On the day of testosterone injection (i.e. day 1 of each cycle) patients will begin therapy with oral etoposide at a dose of 100 mg/day given in divided doses (one 50 mg etoposide capsule q 12 h) for 14 consecutive days. This dose was selected based on Phase II studies of the combination of oral estramustine and oral etoposide. In these trials, myelosuppression was observed when etoposide was given for 21 days out of a 28 day cycle. Therefore, to minimize toxicity, in this study etoposide will be administered for 14 days of a 28 day cycle.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  lead OTHER

Principal Investigators

• Samuel Denmeade, MD · Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center

• Alberto J Pacheco, BA · Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center

• Ting Wang, MS · Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-03-31

Primary Completion

2014-10-31

Completion

2014-10-31

Countries

• United States

Study Locations