Clinical Trials /

A Study of Docetaxel + ARN-509 in Castration-Resistant Prostate Cancer

NCT03093272

Description:

This research study is studying a combination of drugs as a possible treatment for castration-resistant prostate cancer. The interventions involved in this study are: - Docetaxel (a type of chemotherapy) - Apalutamide (the study medication, also known as ARN-509) - Prednisone (a corticosteroid given to prevent reactions to docetaxel). - Leuprolide acetate (also known as Lupron, a GnRH agonist or similar drug which is standard of care, causes chemical castration which greatly lowers the level of testosterone in the body)

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Docetaxel + ARN-509 in Castration-Resistant Prostate Cancer
  • Official Title: A Phase 2 Study of Docetaxel Plus Apalutamide in Castration-Resistant Prostate Cancer Patients Post Abiraterone Acetate

Clinical Trial IDs

  • ORG STUDY ID: 16-485
  • NCT ID: NCT03093272

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
Leuprolide AcetateLupron InjectionARN-509 Combined With Docetaxel
PrednisoneDeltasoneARN-509 Combined With Docetaxel
DocetaxelDocefrez, TaxotereARN-509 Combined With Docetaxel
ApalutamideARN-509ARN-509 Combined With Docetaxel

Purpose

This research study is studying a combination of drugs as a possible treatment for castration-resistant prostate cancer. The interventions involved in this study are: - Docetaxel (a type of chemotherapy) - Apalutamide (the study medication, also known as ARN-509) - Prednisone (a corticosteroid given to prevent reactions to docetaxel). - Leuprolide acetate (also known as Lupron, a GnRH agonist or similar drug which is standard of care, causes chemical castration which greatly lowers the level of testosterone in the body)

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational intervention to learn whether the intervention works
      in treating a specific disease. "Investigational" means that the intervention is being
      studied.

      Apalutamide is considered an investigational product, which is believed to reduce the growth
      of prostate cancer cells. The FDA (the U.S. Food and Drug Administration) has not approved
      apalutamide as a treatment for any disease, but it is being studied in prostate cancer.
      Docetaxel is an approved therapy for this type of cancer. The FDA has not approved the
      combination of the two drugs in any use.

      In this research study, the investigators are evaluating the combination of two drugs,
      docetaxel with apalutamide. The investigators will keep track of participants'
      prostate-specific antigen (PSA), scans, and overall health to determine how well this drug
      combination works at treating this type of cancer.
    

Trial Arms

NameTypeDescriptionInterventions
ARN-509 Combined With DocetaxelExperimentalApalutamide (ARN-509) will be taken orally at home daily Docetaxel will be administered every 3 weeks intravenously Prednisone will be taken orally twice daily Leuprolide Acetate will be administered at the specification of the physician
  • Leuprolide Acetate
  • Prednisone
  • Docetaxel
  • Apalutamide

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma of the prostate

          -  Castration-resistant prostate cancer requires the following criteria:

               -  A castrate level of testosterone (< 50ng/dL)

               -  Prostate cancer progression on or since last treatment as documented by PSA rise
                  or bone progression according to PCWG2 or soft tissue radiographic progression
                  according to RECIST criteria Version 1.1

               -  If on anti-androgen, will need to show no PSA decline after at least a 6 week
                  withdrawal period from the last dose of bicalutamide or nilutamide or 4 weeks
                  from last flutamide dose

               -  Will require a 2 week washout period from last dose of ketoconazole, abiraterone
                  acetate or radiation

          -  Treatment with abiraterone acetate for CRPC in the past is required. Does not need to
             be the last treatment prior to enrollment.

          -  There is no limit to number of prior therapies

          -  Metastatic disease by bone scan or other nodal or visceral lesions on CT or MRI

          -  Age ≥ 18 years

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (See Appendix
             A)

          -  Adequate organ function as evaluated by the following laboratory criteria:

               -  Hemoglobin ≥ 9g/dL; no transfusions and erythropoietin supplementation permitted
                  within the last 3 months

               -  Absolute neutrophil count (ANC) ≥ 1500/µL

               -  Platelet count ≥ 100 x 10^9/L

               -  Total bilirubin ≤ upper limit of normal (ULN, Note: In subjects with Gilbert's
                  syndrome, if total bilirubin is ≥ 1.5 × ULN, measure direct and indirect
                  bilirubin and if direct bilirubin is ≤ ULN, subject may be eligible)

               -  AST and ALT < 2.5 x ULN or < 5x the ULN if liver metastasis

               -  Serum creatinine < 2.0 × ULN or creatinine clearance > 30cc/min

               -  Serum albumin ≥ 3.0 g/dL

               -  Serum potassium ≥ 3.5 mmol/L (if < 3.5, can be repleted and reassess for
                  eligibility as long as stable off potassium supplementation for > 48 hrs)

          -  Ability to swallow the study drug as a whole tablet

          -  The effects of apalutamide and docetaxel on the developing human fetus are unknown.
             For this reason and because chemotherapeutic agents are known to be teratogenic, men
             must agree to use adequate contraception. Specifically, they must agree to use a
             condom (even men with vasectomies) and another effective method of birth control if he
             is having sex with a woman of childbearing potential or agree to use a condom if he is
             having sex with a woman who is pregnant while on study drug and for 3 months following
             the last dose of study drug. They must also agree not to donate sperm during the study
             and for 3 months after receiving the last dose of study drug.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Pathology consistent with majority of specimen having small cell carcinoma of the
             prostate (prostate cancer with neuroendocrine features is acceptable).

          -  Prior treatment with enzalutamide for CPRC; non-CRPC use allowed (e.g., neoadjuvant,
             combined with radiation for localized disease and didn't progress while on it in those
             settings)

          -  Prior treatment with docetaxel chemotherapy except if > 12 months since it was given
             in either the neoadjuvant or adjuvant setting or for hormone sensitive disease (e.g.,
             CHAARTED population)

          -  Presence of untreated brain metastasis

          -  Seizure or known condition that may pre-dispose to seizure (including but not limited
             to prior stroke, transient ischemic attack within 1 year prior to randomization, brain
             arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas
             that are causing edema or mass effect). Loss of consciousness within 12 months may be
             permitted upon discussion with study PI.

          -  Medications known to lower the seizure threshold must be discontinued or substituted
             at least 4 weeks prior to study entry.

          -  Current, recent (within 4 weeks of the first dose of this study), or planned
             participation in an experimental drug study

          -  Persistent grade > 1 (NCI CTCAE v4.0) AEs due to investigational drugs that were
             administered more than 14 days before study enrollment.

          -  Radiation within 2 weeks prior to entering the study

          -  Peripheral neuropathy ≥ Grade 2.

          -  Current evidence of any of the following:

               -  Uncontrolled hypertension

               -  Gastrointestinal disorder affecting absorption

               -  Active infection (e.g., human immunodeficiency virus [HIV] or viral hepatitis) or
                  other medical condition that would make prednisone/prednisolone (corticosteroid)
                  use contraindicated

          -  Uncontrolled intercurrent illness including, but not limited to, severe or unstable
             angina, myocardial infarction, symptomatic congestive heart failure (defined as New
             York Heart Association Grade II or greater), arterial or venous thromboembolic events
             (e.g., pulmonary embolism), or clinically significant ventricular arrhythmias,
             significant vascular disease (e.g. aortic aneurysm, aortic dissection), or symptomatic
             peripheral vascular disease within 6 months prior to randomization.

          -  Psychiatric illness/social situations that would limit compliance with study
             requirements.

          -  Any condition that in the opinion of the investigator, would preclude participation in
             this study

          -  History of allergic reactions or severe hypersensitivity reactions to drugs formulated
             with polysorbate 80 or antisense oligonucleotides.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to apalutamide or docetaxel

          -  Participants receiving any medications or substances that are strong inhibitors or
             inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly
             changing, it is important to regularly consult a frequently-updated list such as
             http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as
             the Physicians' Desk Reference may also provide this information. As part of the
             enrollment/informed consent procedures, the patient will be counseled on the risk of
             interactions with other agents, and what to do if new medications need to be
             prescribed or if the patient is considering a new over-the-counter medicine or herbal
             product.

          -  Inability to comply with study and/or follow-up procedures
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival
Time Frame:4 months
Safety Issue:
Description:To evaluate progression-free survival on the combination of docetaxel plus apalutamide

Secondary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events according to NCI CTCAE v4.0
Time Frame:2 years
Safety Issue:
Description:All adverse events recorded during the trial that are new or worsening from the time of first dose of treatment will be summarized for the safety population.
Measure:Dose-Limiting Toxicities in the Safety Lead-in Group (first 6 patients)
Time Frame:6 months
Safety Issue:
Description:Specific adverse events will be recorded during the safety lead-in phase of 6 patients. Any toxicities considered unacceptable during this time will be considered a dose-limiting toxicity and will be summarized among all patients evaluable for a dose-limiting toxicity.
Measure:Maximum Blood Concentration (Cmax) for Docetaxel Pharmacokinetic Analysis
Time Frame:2 years
Safety Issue:
Description:Maximum blood concentration (Cmax) and time of maximum blood concentration (tmax) will be determined by visual inspection.
Measure:Area Under the Curve (AUC) for Docetaxel Pharmacokinetic Analysis
Time Frame:2 years
Safety Issue:
Description:The area under the blood concentration-time curve (linear trapezoidal rule) will be determined between 0-24 hours (AUC0-24).
Measure:Time to Progression
Time Frame:2 years
Safety Issue:
Description:Radiologic time to progression and PSA progression will be analyzed using the Kaplan-Meier Method.
Measure:Time to Treatment Failure
Time Frame:2 years
Safety Issue:
Description:Time to treatment failure (including progression and intolerability) will be analyzed using the Kaplan-Meier Method.
Measure:Objective Response Rate
Time Frame:2 years
Safety Issue:
Description:Objective Response Rate
Measure:PSA Response
Time Frame:2 years
Safety Issue:
Description:Will be assessed according to Prostate Cancer Working Group 2 criteria
Measure:Serum PSA Change From Baseline
Time Frame:12 weeks
Safety Issue:
Description:The maximum percent PSA change (rise or fall) from baseline to after 12 weeks on study. It will be summarized using box-whisker plots and waterfall plots for each treatment arm.
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:Overall Survival

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Prostate Cancer

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