- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02903160
Prostate Cancer Intensive, Non-Cross Reactive Therapy (PRINT) for Castration Resistant Prostate Cancer (CRPC)
Clinical Trial of a Rapidly Cycling, Non-Cross Reactive Regimen of Approved Therapeutic Agents to Treat Prostate Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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New York
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New York, New York, United States, 10028
- Icahn School of Medicine at Mount Sinai
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New York, New York, United States, 10011
- Mount Sinai Beth Israel
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Histologically or cytologically confirmed adenocarcinoma of the prostate
- Metastatic castrate resistant prostate cancer, defined by progressive disease based on either rising PSA, new bone metastases, or progression of measurable disease on standard imaging, according to PCWG2 guidelines, despite androgen deprivation therapy
- Ongoing androgen deprivation therapy with a GnRH analogue, GnRH antagonist, or bilateral orchiectomy
- ECOG performance status 0-1
- Serum testosterone level < 50 ng/dL
- Absolute neutrophil count > 1,500/μL, platelet count > 100,000/μL, and hemoglobin > 9 g/dL
- Creatinine < 2 mg/dL
- Total bilirubin < 1 times the upper limit of normal, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 1.5 times the upper limit of normal
Exclusion Criteria:
- History of uncontrolled seizure disorder
Clinically significant cardiovascular disease including:
- Myocardial infarction or uncontrolled angina within 6 months
- Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past
- Uncontrolled hypertension as indicated by a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the screening visit
- Have used or plan to use from 30 days prior to enrollment through the end of the study medication known to lower the seizure threshold or prolong the QT interval
- Major surgery within 4 weeks of enrollment
- Radiation therapy within 4 weeks of enrollment
- Prior use of abiraterone acetate, enzalutamide, docetaxel, cabazitaxel, carboplatin, or radium-223 for the treatment of castration-resistant disease
- Prior docetaxel use in the hormone-sensitive disease setting is allowed, but must be completed ≥ 4 weeks prior to enrollment
- Prior sipuleucel-T use is allowed, but must be completed ≥ 4 weeks prior to enrollment
- Concurrent use of zoledronic acid or denosumab is allowed on study
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: Intensive, Non-Cross Reactive Therapy
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
|
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Disease Progression
Time Frame: 47.8 months
|
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. |
47.8 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (OS)
Time Frame: 47.8 months
|
Overall survival defined as the time of study entry to death from any cause.
|
47.8 months
|
Overall Rate of Survival
Time Frame: 40 months
|
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
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40 months
|
Number of Participants With PSA Response Rate >90%
Time Frame: up to 36 weeks
|
PSA response rate - >90% decrease in PSA compared to baseline
|
up to 36 weeks
|
Number of Participants With PSA Response Rate >=50%
Time Frame: up to 36 weeks
|
Number of participants with PSA response rate >=50% decrease in PSA compared to baseline
|
up to 36 weeks
|
Number of Participants With PSA Progression Compared to Baseline.
Time Frame: up to 36 weeks
|
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:
In participants whose PSA value from baseline has not declined from baseline, progression is defined by:
|
up to 36 weeks
|
Number of Participants With Stable PSA as Compared to Baseline
Time Frame: up to 36 weeks
|
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.
|
up to 36 weeks
|
Number of Participants With Normal Alkaline Phosphatase Levels
Time Frame: baseline and 36 weeks
|
Number of participants who converted from elevated to normal range of alkaline phosphatase levels at 9 months from baseline
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baseline and 36 weeks
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Collaborators and Investigators
Investigators
- Principal Investigator: Bobby Liaw, MD, Icahn School of Medicine at Mount Sinai
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Urogenital Diseases
- Male Urogenital Diseases
- Genital Diseases, Male
- Genital Diseases
- Prostatic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Cytochrome P-450 Enzyme Inhibitors
- Hormone Antagonists
- Steroid Synthesis Inhibitors
- Carboplatin
- Prednisone
- Abiraterone Acetate
- Radium Ra 223 dichloride
Other Study ID Numbers
- GCO 16-1593
- CABAZL07459 (Other Identifier: Sanofi)
- ONC-2014-168 (Other Identifier: Bayer)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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