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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: Abiraterone acetate; Drug: Prednisone; Drug: Radium-223 dichloride; Drug: cabazitaxel; Drug: Carboplatin; Drug: Enzalutamide	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Trial of a Rapidly Cycling, Non-Cross Reactive Regimen of Approved Therapeutic Agents to Treat Prostate Cancer
• Actual Study Start Date: January 13, 2017
• Actual Primary Completion Date: November 15, 2021
• Actual Study Completion Date: November 15, 2021

Arms and Interventions

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	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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, New York

Mount Sinai Beth Israel

New York, New York, United States, 10011

Icahn School of Medicine at Mount Sinai

New York, New York, United States, 10028

Sponsors and Collaborators

Icahn School of Medicine at Mount Sinai

Sanofi

Bayer

Investigators

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

More Information

• Responsible Party: Bobby Liaw, Assistant Profesor, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT02903160
• Other Study ID Numbers: GCO 16-1593; CABAZL07459 ( Other Identifier: Sanofi ); ONC-2014-168 ( Other Identifier: Bayer )
• First Posted: September 16, 2016
• Last Update Posted: December 30, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Bobby Liaw, Icahn School of Medicine at Mount Sinai:

Castration resistant; Prostate cancer; Metastatic; First-line; Treatment naive; Rapidly cycling; Non-cross resistant

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Prednisone; Carboplatin; Abiraterone Acetate; Radium Ra 223 dichloride; Antineoplastic Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors