Clinical Trials /

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

NCT02903160

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: GCO 16-1593
  • SECONDARY ID: CABAZL07459
  • SECONDARY ID: ONC-2014-168
  • NCT ID: NCT02903160

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
Abiraterone acetateIntensive, Non-Cross Reactive Therapy
PrednisoneIntensive, Non-Cross Reactive Therapy
Radium-223 dichlorideIntensive, Non-Cross Reactive Therapy
cabazitaxelIntensive, Non-Cross Reactive Therapy
CarboplatinIntensive, Non-Cross Reactive Therapy
EnzalutamideIntensive, Non-Cross Reactive Therapy

Purpose

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 + Radium-223; 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.
    

Trial Arms

NameTypeDescriptionInterventions
Intensive, Non-Cross Reactive TherapyExperimentalProstate Cancer Rapidly cycling, Intensive, Non-Cross Reactive Therapy (PRINT) Rapidly cycling, consecutive treatment modules: 1. Abiraterone acetate + Radium-223; 2. Cabazitaxel + Carboplatin; 3. Enzalutamide + Radium-223
  • Abiraterone acetate
  • Prednisone
  • Radium-223 dichloride
  • cabazitaxel
  • Carboplatin
  • Enzalutamide

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/mL

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Time to disease progression
Time Frame:average 24 months
Safety Issue:
Description: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

Measure:Overall survival
Time Frame:up to 24 months
Safety Issue:
Description:
Measure:PSA response rate
Time Frame:up to 24 months
Safety Issue:
Description:
Measure:Changes to alkaline phosphatase levels
Time Frame:baseline and 24 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Icahn School of Medicine at Mount Sinai

Trial Keywords

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

Last Updated

September 12, 2016