Trial record 7 of 50 for:    mdv3100 | Open Studies

RE-sensitizing With Supraphysiologic Testosterone to Overcome REsistant (The RESTORE Study) (Restore)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Sidney Kimmel Comprehensive Cancer Center
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center Identifier:
First received: March 4, 2014
Last updated: June 25, 2014
Last verified: June 2014

Single-arm, single site, open label study of the effects of parenteral testosterone followed by enzalutamide or abiraterone in men with metastatic CRPC who previously progressed on either of these agents. The study will enroll two cohorts of patients: men with metastatic CRPC who have progressed on enzalutamide (Cohort A); and men with metastatic CRPC who have progressed on abiraterone acetate (Cohort B).

Condition Intervention Phase
Prostate Cancer
Drug: Testosterone cypionate
Drug: Testosterone Enanthate
Drug: Abiraterone acetate
Drug: Enzalutamide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study to Determine Sequential Response to Bipolar Androgen Therapy (BAT) Followed by Enzalutamide or Abiraterone Post-BAT in Men With Prostate Cancer Progressing on Combined Androgen Ablative Therapies

Resource links provided by NLM:

Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • PSA response to Bipolar Androgen Therapy [ Time Frame: On average at 18 months ] [ Designated as safety issue: Yes ]
    PSA response to BAT (≥50% PSA reduction from pre-BAT baseline level).

  • PSA response to enzalutamide or abiraterone acetate post Bipolar Androgen Therapy [ Time Frame: On average at 24 months ] [ Designated as safety issue: No ]
    PSA response to enzalutamide or abiraterone acetate post-BAT (≥50% PSA reduction from baseline PSA level obtained at initiation of enzalutamide or abiraterone acetate post-BAT)

Secondary Outcome Measures:
  • PSA progression on enzalutamide or abiraterone acetate post-BAT [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]
    Time to PSA progression on enzalutamide or abiraterone acetate post-BAT

  • PSA progression on BAT (Bipolar Androgen Therapy ) [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]
    Time to PSA progression on BAT

  • Measurable disease response [ Time Frame: On average at 18 months ] [ Designated as safety issue: Yes ]

    Measurable disease response post-BAT and post-treatment with enzalutamide or abiraterone acetate post-BAT.

    1. For soft tissue lesions, based on RECIST 1.1.
    2. For bone disease, based on PCWG2 criteria.

  • initiation of docetaxel chemotherapy [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]
    Time to initiation of docetaxel chemotherapy

  • Quality of life [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]
    The following quality of life surveys will be administered: FACIT-F, RANDSF-36, Brief Pain Inventory, IIEF and PANAS,

  • Safety and Tolerability [ Time Frame: On average at 18 months ] [ Designated as safety issue: Yes ]
    Adverse events will be collected at each clinic visit and classified for severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

  • Fasting glucose [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]
    Fasting blood glucose level

  • hemoglobin A1c [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]
    hemoglobin A1c level

  • Fasting insulin [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]
    Fasting insulin levels

  • Serum N-telopeptide [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]
    Serum N-telopeptide levels

  • Osteocalcin [ Time Frame: On average at 18 months ] [ Designated as safety issue: No ]
    Osteocalcin levels

Estimated Enrollment: 60
Study Start Date: June 2014
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Post-abiraterone or post-enzalutamide
Men with castration-resistant prostate cancer who have progressed on either abiraterone or enzalutamide will be enrolled to this arm. These patients will then receive intramuscular injections with testosterone cypionate 400 mg every 28 days or testosterone enanthate 400 mg every 28 days. Upon progression on testosterone cypionate or enanthate, men will be retreated with either abiraterone 1000 mg by mouth daily or enzalutamide 160 mg by mouth daily, depending on which drug they previously received.
Drug: Testosterone cypionate
DEPO-Testosterone Injection, for intramuscular injection, contains testosterone cypionate which is the oil-soluble of the androgenic hormone testosterone. Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. DEPO-Testosterone Injection is available in two strengths, 100 mg/mL and 200 mg/mL testosterone cypionate.
Other Name: DEPO-Testosterone Injection
Drug: Testosterone Enanthate
Testosterone Enanthate Injection, for intramuscular injection, contains testosterone enanthate which is the oil-soluble ester of the androgenic hormone testosterone. Enanthate Injection is available as a colorless to pale yellow solution. Each mL contains 200 mg testosterone enanthate in sesame oil with 5 mg chlorobutanol as a preservative.
Other Name: Delatestryl
Drug: Abiraterone acetate
Abiraterone is an inhibitor of CYP17 (17α-hydroxylase/C17,20-lyase). Each ZYTIGA tablet contains 250 mg of abiraterone acetate.
Other Name: Zytiga
Drug: Enzalutamide
XTANDI is provided as liquid-filled soft gelatin capsules for oral administration. Each capsule contains 40 mg of enzalutamide as a solution in caprylocaproyl polyoxylglycerides.
Other Name: Xtandi

Detailed Description:

The trial will enroll up to 60 patients, 30 for each cohort. Eligible patients will continue on androgen ablative therapy with LHRH agonist (i.e. Zoladex, Trelstar, Eligard or Lupron) if not surgically castrated to suppress endogenous testosterone production. Patients will also receive intramuscular injection with either testosterone cypionate or testosterone enanthate at a dose of 400 mg every 28 days. This dosing scheme was designed to produce rapidly fluctuating serum testosterone levels from the supraphysiologic to the near-castrate range (i.e. Bipolar Androgen Therapy [BAT]). Assessments for response to testosterone will be made approximately every 3 months. Upon displaying evidence of progression, patients will then go on to receive either abiraterone or enzalutamide (whichever agent they had previously progressed on prior to study enrollment).


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Performance status ≤2
  2. Age ≥18 years
  3. Histologically-confirmed adenocarcinoma of the prostate
  4. Treated with continuous androgen ablative therapy (either surgical castration or LHRH agonist)
  5. Documented castrate level of serum testosterone (<20 ng/dl)
  6. Must have progressed on prior treatment with enzalutamide or abiraterone acetate + prednisone (by PSA criteria or radiographically).
  7. Patients with rising PSA on two successive measurements at least two weeks apart
  8. Prior treatment with up to 2 additional second line hormone therapies, including ketoconazole is allowed.
  9. Patients who have progressed on both enzalutamide and abiraterone acetate are eligible and post-BAT will be retreated with the last second line agent they had received (e.g. patient receiving abiraterone then enzalutamide would receive retreatment with enzalutamide post-BAT).
  10. Patients must be withdrawn from enzalutamide or abiraterone acetate for ≥ 4 weeks and have documented PSA increase after the withdrawal period.
  11. Patients receiving prednisone in conjunction with abiraterone acetate must be weaned off prednisone prior to starting BAT.
  12. Acceptable liver function:

    1. Bilirubin < 2.5 times institutional upper limit of normal (ULN)
    2. AST (SGOT) and ALT (SGPT) < 2.5 times ULN
  13. Acceptable renal function:

    a.Serum creatinine < 2.5 times ULN, OR

  14. Acceptable hematologic status:

    1. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L)
    2. Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)
    3. Hemoglobin ≥ 9 g/dL.
  15. At least 4 weeks since prior surgery with full recovery (no persistent toxicity ≥ Grade 1)
  16. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Pain due to metastatic prostate cancer requiring opioid analgesics
  2. >5 sites of visceral disease in lung or liver (nonspecific lung nodules ≤1 cm in diameter are permitted).
  3. Prior treatment with docetaxel or cabazitaxel.
  4. Prior seizures while on enzalutamide therapy.
  5. Requires urinary catheterization for voiding due to obstruction secondary to prostatic enlargement thought to be due to prostate cancer or benign prostatic hyperplasia.
  6. 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).
  7. Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study
  8. Active uncontrolled infection, including known history of AIDS or hepatitis B or C.
  9. Prior history of a thromboembolic event within the last two years and not currently on systemic anticoagulation.
  10. Prior myocardial infarction within one year of study entry.
  11. Hematocrit >50%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure [per Endocrine Society Clinical Practice Guidelines (67)].
  12. Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02090114

Contact: Avery Spitz 410-502-2043
Contact: Rana Sullivan 410-614-6337

United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231
Contact: Avery Spitz    410-502-2043   
Contact: Rana Sullivan    410-614-6337   
Principal Investigator: Samuel Denmeade, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Principal Investigator: Samuel Denmeade, MD Johns Hopkins School of Medicine - Sidney Kimmel Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center Identifier: NCT02090114     History of Changes
Other Study ID Numbers: J1416, NA_00093344
Study First Received: March 4, 2014
Last Updated: June 25, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
Bipolar Androgen Therapy
Androgen Ablative Therapies

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Testosterone 17 beta-cypionate
Testosterone enanthate
Testosterone undecanoate
Anabolic Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on October 23, 2014