- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01084759
A Pilot Study of Parenteral Testosterone and Oral Etoposide as Therapy for Men With Castration Resistant Prostate Cancer
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Maryland
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Baltimore, Maryland, United States, 21205
- Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Performance status ≤2
- Documented adenocarcinoma of the prostate with histologic confirmation
- Treated with continuous androgen ablative therapy (either surgical castration or LHRH agonist for ≥ 1 year)
- Documented castrate level of serum testosterone (<50 ng/dl)
- Evidence of rising PSA on two successive dates > 1 month apart
- Treatment with ≤ 2 prior chemotherapeutic regimens allowed
- Treatment with ≤2 prior second line hormone therapies allowed.
- Prior treatment with ketoconazole is allowed.
- Patients must be withdrawn from antiandrogens for ≥ 6 weeks and have documented PSA increase after the 6 week withdrawal period.
- Patients with rising PSA only or ≤ 5 sites of asymptomatic bone metastases and < 10 total sites of disease including bone and soft tissue documented within 28 days of enrollment on trial.
Patients will considered for repeat treatment with testosterone if they meet the following criteria:
- Had either PSA decline from baseline following treatment with testosterone or had return of PSA levels to pretreatment baseline once serum testosterone reached a castrate level.
- Must continue to meet inclusion/exclusion criteria as described above
- Must have been off testosterone therapy for ≥ 3 months
- Must have castrate level of serum testosterone
- Must have evidence of rising PSA on two occasions at least 2 weeks apart
- Are allowed to have had additional treatment with up to 2 additional hormonal therapies that include anti-androgens (e.g. flutamide, bicalutamide, nilutamide, enzalutamide), CYP17 inhibitors (e.g. ketoconazole, abiraterone acetate) or other investigational hormonal therapies.
Exclusion Criteria:
- Evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone (e.g. femoral metastases with concern over fracture risk, spinal metastases with concern over spinal cord compression, lymph node disease with concern for ureteral obstruction)
- Abnormal liver function (bilirubin, AST, ALT ≥ 2 x upper limit of normal)
- Abnormal kidney function (serum creatinine ≥ 2 x upper limit of normal)
- Inability to provide informed consent
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Etoposide and Testosterone
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).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.
|
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.
Other Names:
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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Patients Completing at Least 3 Months of Therapy With a PSA Below Baseline.
Time Frame: 3 months
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3 months
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Time to PSA Progression
Time Frame: 2 years
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Time to a PSA increase above the PSA level obtained after 3 months on testosterone treatment over two successive measurements 2 weeks apart.
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2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With RECIST Response (i.e. Complete Response or Partial Response)
Time Frame: 2 years
|
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan or MRI.
Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
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2 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Samuel Denmeade, MD, Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
- Study Chair: Alberto J Pacheco, BA, Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
- Study Director: Ting Wang, MS, Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Prostatic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Androgens
- Anabolic Agents
- Etoposide
- Testosterone
- Methyltestosterone
- Testosterone undecanoate
- Testosterone enanthate
- Testosterone 17 beta-cypionate
Other Study ID Numbers
- J09121, NA_00033419
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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