Phase 2
N=96
RE-sensitizing With Supraphysiologic Testosterone to Overcome REsistance (The RESTORE Study)
Prostate Cancer
Bottom Line
View on ClinicalTrials.gov: NCT02090114 ↗Enrolled (actual)
96
Serious AEs
13.5%
Results posted
Jun 2022
Primary outcome: Primary: Prostate Specific Antigen (PSA) Response to Bipolar Androgen Therapy (BAT) — 9; 5; 4; 2 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Testosterone cypionate (Drug); Testosterone Enanthate (Drug); Abiraterone acetate (Drug); Enzalutamide (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Male
- Sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Primary completion
- Nov 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Prostate Specific Antigen (PSA) Response to Bipolar Androgen Therapy (BAT) |
9; 5; 4; 2 | — |
| PRIMARY PSA Response to Enzalutamide or Abiraterone Acetate Post Bipolar Androgen Therapy |
15; 3; 2 | — |
| SECONDARY PSA Progression on Enzalutamide or Abiraterone Acetate or Castrate Levels Post-BAT |
5.5; 3.7; NA | — |
| SECONDARY PSA Progression on BAT (Bipolar Androgen Therapy ) |
3.3; 3.2; 0.93; 3 | — |
| SECONDARY Disease Response as Defined by RECIST 1.1 (Soft Tissue Lesions) and PCWG2 Criteria (Bone Lesions) |
6; 2; 4; 0 | — |
| SECONDARY Initiation of Docetaxel Chemotherapy |
— | — |
| SECONDARY Quality of Life (QoL) as Assessed by FACIT-F Score |
13.28; 16.86; 13; 10.64; 13.85; 11.55 | — |
| SECONDARY Safety and Tolerability as Assessed by Number of Participants With Adverse Events |
30; 29; 29; 7 | — |
| SECONDARY Quality of Life (QoL) as Assessed by RANDSF-36 |
72.23; 64.36; 69.72; 71.76; 73.97; 73.40 | — |
| SECONDARY Quality of Life (QoL) as Assessed by BPI |
— | — |
| SECONDARY Quality of Life (QoL) as Assessed by IIEF |
8; 7.33; 12.56; 24.13; 24.94; 22.44 | — |
| SECONDARY Quality of Life (QoL) as Assessed by PANAS |
46.15; 48; 41.24; 45.1; 45.22; 44.48 | — |
Summary
Single-arm, single site, open label study of the effects of parenteral testosterone followed by enzalutamide, abiraterone or castration-only therapy in men with metastatic CRPC who previously progressed on one of these forms of therapy. The study will enroll four cohorts of patients: men with metastatic CRPC who have progressed on enzalutamide (Cohort A; n=30); men with metastatic CRPC who have progressed on abiraterone acetate (Cohort B; n=30); men with metastatic CRPC who have progressed on first line castration-only therapy (Cohort C; n=30); men with metastatic CRPC with inactivating somatic or germline mutations in ≥2 of the genes TP53, PTEN, or RB1 (Cohort D; n=20).
Eligibility Criteria
Inclusion Criteria
- Performance status ≤2
- Age ≥18 years
- Histologically-confirmed adenocarcinoma of the prostate
- Progressing on continuous androgen ablative therapy (either surgical castration or LHRH agonist).
- Documented castrate level of serum testosterone ( 12 months since last dose of docetaxel
- For Cohort D, one line of prior chemotherapy with docetaxel or cabazitaxel for metastatic castrate resistant prostate cancer is allowed
- Acceptable liver function:
- Bilirubin 5 sites of visceral disease in lung or liver (nonspecific lung nodules ≤1 cm in diameter are permitted).
- Prior treatment with docetaxel or cabazitaxel for metastatic castration-resistant prostate cancer is prohibited.
- Prior treatment with one line of chemotherapy for metastatic castration-resistant prostate cancer is allowed for Cohort D
- Requires urinary catheterization for voiding due to obstruction secondary to prostatic enlargement thought to be due to prostate cancer or benign prostatic hyperplasia
- 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).
- 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.
- Active uncontrolled infection, including known history of AIDS or hepatitis B or C.
- Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
- Prior history of a thromboembolic event within the last two years and not currently on systemic anticoagulation.
- Hematocrit >50%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure [per Endocrine Society Clinical Practice Guidelines (67)].
Data sourced from ClinicalTrials.gov (NCT02090114). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.