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

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ClinicalTrials.gov Identifier: NCT02903160
Recruitment Status : Recruiting
First Posted : September 16, 2016
Last Update Posted : November 2, 2018
Sponsor:
Collaborators:
Sanofi
Bayer
Information provided by (Responsible Party):
Bobby Liaw, Icahn School of Medicine at Mount Sinai

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
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
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

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




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 ]


Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02903160


Contacts
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Contact: Bobby Liaw, MD 212-604-6010 bobby.liaw@mountsinai.org

Locations
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United States, New York
Mount Sinai Beth Israel Recruiting
New York, New York, United States, 10011
Contact: Bobby Liaw, MD    212-604-6010    bobby.liaw@mountsinai.org   
Principal Investigator: Bobby Liaw, MD         
Mount Sinai West Withdrawn
New York, New York, United States, 10019
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10028
Contact: William Oh, MD    212-659-5549    william.oh@mssm.edu   
Principal Investigator: William Oh, MD         
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
Sanofi
Bayer
Investigators
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Principal Investigator: Bobby Liaw, MD Icahn School of Medicine at Mount Sinai

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Responsible Party: Bobby Liaw, Assistant Profesor, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT02903160     History of Changes
Other Study ID Numbers: GCO 16-1593
CABAZL07459 ( Other Identifier: Sanofi )
ONC-2014-168 ( Other Identifier: Bayer )
First Posted: September 16, 2016    Key Record Dates
Last Update Posted: November 2, 2018
Last Verified: October 2018
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:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carboplatin
Prednisone
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