Prostate Cancer Intensive, Non-Cross Reactive Therapy (PRINT) for Castration Resistant Prostate Cancer (CRPC)

• ClinicalTrials.gov Identifier: NCT02903160
• Recruitment Status: Completed
• First Posted: September 16, 2016
• Last Update Posted: December 30, 2021
• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Sanofi; Bayer
• Information provided by (Responsible Party): Bobby Liaw, Icahn School of Medicine at Mount Sinai

Tracking Information

• First Submitted Date: September 7, 2016
• First Posted Date: September 16, 2016
• Last Update Posted Date: December 30, 2021
• Actual Study Start Date: January 13, 2017
• Actual Primary Completion Date: November 15, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 12, 2016)

Time to disease progression [ Time Frame: average 24 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 12, 2016)

• Overall survival [ Time Frame: up to 24 months ]
• PSA response rate [ Time Frame: up to 24 months ]
• Changes to alkaline phosphatase levels [ Time Frame: baseline and 24 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Prostate Cancer Intensive, Non-Cross Reactive Therapy (PRINT) for Castration Resistant Prostate Cancer (CRPC)
• Official Title: Clinical Trial of a Rapidly Cycling, Non-Cross Reactive Regimen of Approved Therapeutic Agents to Treat Prostate Cancer
• Brief Summary: 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.

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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Prostate Cancer

Intervention

• Drug: Abiraterone acetate
  Abiraterone acetate 1000 mg PO daily
• Drug: Prednisone
  5 mg PO twice a day
• Drug: Radium-223 dichloride
  50 kBq/kg IV monthly
• Drug: cabazitaxel
  25 mg/m2 IV every 3 weeks
• Drug: Carboplatin
  Carboplatin AUC 4 IV every 3 weeks
• Drug: Enzalutamide
  160 mg PO daily

Study Arms

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

Interventions:

• Drug: Abiraterone acetate
• Drug: Prednisone
• Drug: Radium-223 dichloride
• Drug: cabazitaxel
• Drug: Carboplatin
• Drug: Enzalutamide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 12, 2016): 40
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: November 15, 2021
• Actual Primary Completion Date: November 15, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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:

  1. Myocardial infarction or uncontrolled angina within 6 months
  2. 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
  3. 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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02903160
• Other Study ID Numbers: GCO 16-1593; CABAZL07459 ( Other Identifier: Sanofi ); ONC-2014-168 ( Other Identifier: Bayer )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Bobby Liaw, Icahn School of Medicine at Mount Sinai
• Original Responsible Party: Same as current
• Current Study Sponsor: Icahn School of Medicine at Mount Sinai
• Original Study Sponsor: Same as current

Collaborators

• Sanofi
• Bayer

Investigators

• Principal Investigator: Bobby Liaw, MD; Icahn School of Medicine at Mount Sinai

• PRS Account: Icahn School of Medicine at Mount Sinai
• Verification Date: December 2021