A Phase 2 interventional study of Abiraterone acetate and Prednisone in Prostate Cancer, sponsored by Icahn School of Medicine at Mount Sinai. Completed at 2 sites in United States. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-02-07.
Sponsored by Icahn School of Medicine at Mount Sinai · Phase 2, Interventional, and Treatment
The purpose of this study is to determine the clinical benefits of using a rapidly cycling, non-cross reactive regimen of FDA-approved prostate cancer therapeutic agents in the management of castration resistant prostate cancer. The hypothesis is that the identification of optimal combinations and sequencing of therapies can help prevent or delay the development of therapeutic drug resistance, and can be safely tolerated.
This phase II clinical trial will explore the efficacy of rapidly cycling non-cross reactive treatment therapies in the treatment of patients with newly diagnosed mCRPC. The primary hypothesis is that the best chance of eliminating or controlling disease is when the cancer is treatment naïve, and has not yet developed therapeutic resistance. By finding an optimal drug deployment strategy of already approved and available treatments for mCRPC, the researchers believe providers can more effectively treat an intrinsically heterogeneous disease, delay/prevent drug resistance, as well as minimize treatment toxicity.
All of the treatment agents selected have well-defined individual toxicity profiles from large phase III trials, but there is limited clinical data about the toxicity profiles of these drugs in combinations. While each agent is generally well tolerated, toxicities remain a significant concern given the older age of the typical mCRPC patient, the comorbid conditions common to this patient population, as well as those borne from previous chronic androgen deprivation therapy.
Each drug in the proposed treatment regimen will be used at their FDA-approved dosing and indication, with the exception of cabazitaxel, which will be used prior to disease demonstration of docetaxel failure, and in combination with carboplatin. The proposed sequencing is rationally designed, and based on each drug's distinct mechanisms of action as well as their toxicity profiles.
The rapidly-cycling treatment regimen contains three, separate, consecutive treatment modules, each lasting 3 months: 1. Abiraterone; 2. Cabazitaxel + Carboplatin; 3. Enzalutamide + Radium-223. Therapeutic agents are delivered as non-cross reactive combinations, in order to achieve optimal therapeutic dosing at each cycle and decrease possibility of significant adverse effects.
To the researcher knowledge, no study has evaluated the use of rapidly cycling, non-cross reactive therapies for the treatment of mCRPC. The hypothesis is that the identification of optimal combinations and sequencing of rapidly cycling non-cross reactive therapies can help prevent or delay the development of therapeutic drug resistance, and can be safely tolerated.
Primary objective is to evaluate the time to disease progression after completion of all modules of the rapidly-cycling, non-cross reactive regimen in patients with mCRPC. Secondary objectives are to evaluate overall survival, prostate-specific antigen (PSA) response rate with each treatment module, changes to alkaline phosphatase level, and assess safety of the rapidly-cycling, non-cross reactive regimen. Additional exploratory objective are to evaluate the correlation of a peripheral whole-blood RNA signature with clinical outcome measures during and after treatment, and to evaluate changes to AR-V7 expression in CTCs with different treatment modalities and clinical outcomes.
6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.
This study's enrollment of 40 is below the median of 58 across 4,822 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →Icahn School of Medicine at Mount Sinai is the lead sponsor of 764 studies on the registry; 181 are open to participants now.
Of its 121 completed or terminated interventional studies of FDA-regulated products, 82 (68%) have results posted.
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Exclusion Criteria:
Clinically significant cardiovascular disease including:
Prostate Cancer Rapidly cycling, Intensive, Non-Cross Reactive Therapy (PRINT) Rapidly cycling, consecutive treatment modules: 1. Abiraterone acetate; 2. Cabazitaxel + Carboplatin; 3. Enzalutamide + Radium-223
Drug: Abiraterone acetate · Drug: Prednisone · Drug: Radium-223 dichloride · Drug: cabazitaxel · Drug: Carboplatin · Drug: Enzalutamide
Abiraterone acetate 1000 mg PO daily
5 mg PO twice a day
50 kBq/kg IV monthly
25 mg/m2 IV every 3 weeks
Carboplatin AUC 4 IV every 3 weeks
160 mg PO daily
Time to Disease Progression
Time to disease progression, as determined by either PSA or radiographic progression, after completion of all modules of the rapidly-cycling, non-cross reactive regimen in patients with mCRPC. Time to progression (TTP) is defined as beginning with the time the first dose of PCD regimen is administered until disease progression.
Time frame: 47.8 months
Overall Survival (OS)
Overall survival defined as the time of study entry to death from any cause.
Time frame: 47.8 months
Overall Rate of Survival
Overall rate of survival at 40 months. Overall rate of Survival as defined by likelihood that a participant on the study is still alive at 40 months follow up
Time frame: 40 months
Number of Participants With PSA Response Rate >90%
PSA response rate - \>90% decrease in PSA compared to baseline
Time frame: up to 36 weeks
Number of Participants With PSA Response Rate >=50%
Number of participants with PSA response rate \>=50% decrease in PSA compared to baseline
Time frame: up to 36 weeks
Number of Participants With PSA Progression Compared to Baseline.
PSA changes was reported globally using a waterfall plot for each module. In participants who have a decline in PSA value from baseline, progression is defined by: * An increase in PSA by 25% above the nadir, AND * An increase in PSA by a minimum of 2 ng/ml, or an increase in PSA to the pre-treatment PSA value, AND * Confirmation by a second PSA at least 3 weeks apart, AND * Occur following at least 12 weeks of therapy, AND * There is no objective evidence of disease response. In participants whose PSA value from baseline has not declined from baseline, progression is defined by: * An increase in PSA by 25% above either the pre-treatment level, or the nadir PSA level (whichever is lowest), AND * An increase in PSA by a minimum of 2 ng/ml, AND * Confirmation by a second PSA at least 3 weeks apart, AND * Occur following at least 12 weeks of therapy, AND * There is no objective evidence of disease response.
Time frame: up to 36 weeks
Number of Participants With Stable PSA as Compared to Baseline
Participants with a 50% PSA decline from their baseline PSA level will be considered responders, provided objective tumor measurements are stable or also demonstrate response. Participants with a 25% PSA increase from their baseline PSA will be considered nonresponders. Participants that do not meet criteria for responder or nonresponder, will be considered to have stable disease.
Time frame: up to 36 weeks
Number of Participants With Normal Alkaline Phosphatase Levels
Number of participants who converted from elevated to normal range of alkaline phosphatase levels at 9 months from baseline
Time frame: baseline and 36 weeks
| Milestone | Intensive, Non-Cross Reactive Therapy |
|---|---|
| Started | 40 |
| Completed | 33 |
| Not completed | 7 |
| Withdrew: Adverse event | 2 |
| Withdrew: Death | 1 |
| Withdrew: Lost to follow-up | 2 |
| Withdrew: Withdrawal by subject | 1 |
| Withdrew: Medical insurance barriers | 1 |
Time to disease progression, as determined by either PSA or radiographic progression, after completion of all modules of the rapidly-cycling, non-cross reactive regimen in patients with mCRPC. Time to progression (TTP) is defined as beginning with the time the first dose of PCD regimen is administered until disease progression.
| weeks | Intensive, Non-Cross Reactive Therapy |
|---|---|
| Time to Disease Progression | 15.2 (10.8 to 23.2) |
Overall survival defined as the time of study entry to death from any cause.
| weeks | Intensive, Non-Cross Reactive Therapy |
|---|---|
| Overall Survival (OS) | NA (NA to NA) |
Overall rate of survival at 40 months. Overall rate of Survival as defined by likelihood that a participant on the study is still alive at 40 months follow up
| percent | Intensive, Non-Cross Reactive Therapy |
|---|---|
| Overall Rate of Survival | 63 (47 to 85) |
PSA response rate - \>90% decrease in PSA compared to baseline
| Participants | Intensive, Non-Cross Reactive Therapy |
|---|---|
| after module 1, 12 weeks | 11 |
| after module 2, 24 weeks | 14 |
| after module 3, 36 weeks | 20 |
Number of participants with PSA response rate \>=50% decrease in PSA compared to baseline
| Participants | Intensive, Non-Cross Reactive Therapy |
|---|---|
| after module 1, 12 weeks | 27 |
| after module 2, 24 weeks | 28 |
| after module 3, 36 weeks | 32 |
PSA changes was reported globally using a waterfall plot for each module. In participants who have a decline in PSA value from baseline, progression is defined by: * An increase in PSA by 25% above the nadir, AND * An increase in PSA by a minimum of 2 ng/ml, or an increase in PSA to the pre-treatment PSA value, AND * Confirmation by a second PSA at least 3 weeks apart, AND * Occur following at least 12 weeks of therapy, AND * There is no objective evidence of disease response. In participants whose PSA value from baseline has not declined from baseline, progression is defined by: * An increase in PSA by 25% above either the pre-treatment level, or the nadir PSA level (whichever is lowest), AND * An increase in PSA by a minimum of 2 ng/ml, AND * Confirmation by a second PSA at least 3 weeks apart, AND * Occur following at least 12 weeks of therapy, AND * There is no objective evidence of disease response.
| Participants | Intensive, Non-Cross Reactive Therapy |
|---|---|
| after module 1, 12 weeks | 4 |
| after module 2, 24 weeks | 4 |
| after module 3, 36 weeks | 0 |
Participants with a 50% PSA decline from their baseline PSA level will be considered responders, provided objective tumor measurements are stable or also demonstrate response. Participants with a 25% PSA increase from their baseline PSA will be considered nonresponders. Participants that do not meet criteria for responder or nonresponder, will be considered to have stable disease.
| Participants | Intensive, Non-Cross Reactive Therapy |
|---|---|
| after module 1, 12 weeks | 2 |
| after module 2, 24 weeks | 1 |
| after module 3, 36 weeks | 1 |
Number of participants who converted from elevated to normal range of alkaline phosphatase levels at 9 months from baseline
| Participants | Intensive, Non-Cross Reactive Therapy |
|---|---|
| Number of Participants With Normal Alkaline Phosphatase Levels | 8 |
Collected over Adverse events were assessed from enrollment up to 48 weeks. All-Cause Mortality was from first dose until death, assessed up to 47.8 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Intensive, Non-Cross Reactive Therapy | 1/33 (3%) | 10/33 (30.3%) | 18/33 (54.5%) |
| Event | Intensive, Non-Cross Reactive Therapy |
|---|---|
| diarrheaGastrointestinal disorders | 2/33 |
| neutrophil count decreasedBlood and lymphatic system disorders | 2/33 |
| hyperglycemiaEndocrine disorders | 1/33 |
| vomitingGastrointestinal disorders | 1/33 |
| nauseaGastrointestinal disorders | 1/33 |
| lymphocyte count decreasedBlood and lymphatic system disorders | 1/33 |
| platelet count decreasedBlood and lymphatic system disorders | 1/33 |
| blood bilirubin increasedHepatobiliary disorders | 1/33 |
| Event | Intensive, Non-Cross Reactive Therapy |
|---|---|
| fatigueGeneral disorders | 18/33 |
| diarrheaGastrointestinal disorders | 17/33 |
| nauseaGastrointestinal disorders | 14/33 |
| lymphocyte count decreasedBlood and lymphatic system disorders | 13/33 |
| white blood cell count decreasedBlood and lymphatic system disorders | 13/33 |
| anorexiaGastrointestinal disorders | 13/33 |
| anemiaBlood and lymphatic system disorders | 13/33 |
| peripheral sensory neuropathyNervous system disorders | 10/33 |
| vomitingGastrointestinal disorders | 9/33 |
| hyperglycemiaEndocrine disorders | 7/33 |
| Age, Continuous(years) | Intensive, Non-Cross Reactive Therapy |
|---|---|
| Mean | 69 (48 to 85) |
| Sex: Female, Male(Participants) | Intensive, Non-Cross Reactive Therapy |
|---|---|
| Female | 0 |
| Male | 40 |
| Race/Ethnicity, Customized(Participants) | Intensive, Non-Cross Reactive Therapy |
|---|---|
| Amerian Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 10 |
| White | 21 |
| Hispanic | 7 |
| More than one race | 0 |
| Unknown or Not Reported | 1 |
| Gleason score(Participants) | Intensive, Non-Cross Reactive Therapy |
|---|---|
| <=6 | 5 |
| 7 | 10 |
| >=8 | 21 |
| Unknown | 4 |
| Prostate-specific antigen (PSA)(ng/mL) | Intensive, Non-Cross Reactive Therapy |
|---|---|
| Median | 9.6 (4.8 to 40.3) |
| Alkaline phosphatase(IU/L) | Intensive, Non-Cross Reactive Therapy |
|---|---|
| Median | 98 (77.8 to 153) |
| Alkaline phosphatase(Participants) | Intensive, Non-Cross Reactive Therapy |
|---|---|
| Elevated (>126 IU/L) | 13 |
| Normal (<=126 IU/L) | 27 |
| Eastern Cooperative Oncology Group (ECOG)(Participants) | Intensive, Non-Cross Reactive Therapy |
|---|---|
| 0 | 27 |
| 1 | 10 |
| unknown | 3 |
1 further baseline measures are reported on the registry.
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Icahn School of Medicine at Mount Sinai