Clinical Trials /

Abiraterone Acetate, Prednisone, and Apalutamide With or Without Ipilimumab or Cabazitaxel and Carboplatin in Treating Patients With Metastatic Castration-Resistant Prostate Cancer

NCT02703623

Description:

This randomized phase II trial studies the side effects and how well abiraterone acetate, prednisone, and apalutamide work with or without ipilimumab or cabazitaxel and carboplatin in treating patients with castration-resistant prostate cancer that has spread to other places in the body. Androgens can cause the growth of prostate cancer cells. Drugs, such as abiraterone acetate and apalutamide may lessen the amount of androgens made by the body. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as prednisone, cabazitaxel, and carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving abiraterone acetate, prednisone, and apalutamide with or without ipilimumab or cabazitaxel and carboplatin may be a better way to treat patients with castration-resistant prostate cancer that has spread to other places in the body.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Dynamic Allocation Modular Sequential Trial of Approved and Promising Therapies in Men With Metastatic Castrate Resistant Prostate Cancer (DynaMO)
  • Official Title: A Dynamic Allocation Modular Sequential Trial of Approved and Promising Therapies in Men With Metastatic Castrate Resistant Prostate Cancer (DynaMO)

Clinical Trial IDs

  • ORG STUDY ID: 2014-0386
  • SECONDARY ID: NCI-2016-00670
  • NCT ID: NCT02703623

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
Abiraterone acetateZytigaARN-509 + Abiraterone + Prednisone
PrednisoneARN-509 + Abiraterone + Prednisone
ARN509ARN-509 + Abiraterone + Prednisone
IpilimumabYervoy, BMS-734016, MDX010ARN-509 + Abiraterone + Prednisone + Ipilimumab
CabazitaxelJevtanaARN-509+Abiraterone+Pred+Cabazitaxel+Carbo
CarboplatinParaplatinARN-509+Abiraterone+Pred+Cabazitaxel+Carbo

Purpose

The goal of this clinical research study is to find out if the combination of apalutamide (also known as ARN-509 or JNJ-5602192), abiraterone acetate, and prednisone can be given with either ipilimumab or cabazitaxel plus carboplatin to control metastatic CRPC. The safety and effectiveness of these drug combinations and their effect on the immune system will also be studied.

Detailed Description

      Study Groups:

      If you are found to be eligible to take part in this study, you will be assigned to Group 1
      and receive apalutamide, abiraterone, and prednisone. After 8 weeks of receiving treatment
      in Group 1, you will then have blood (about 4 teaspoons) drawn for biomarker testing. The
      result of this biomarker test will determine whether you will continue the study in Group 2
      or Group 3.

      If you are found to be eligible for Group 2, you will be randomly assigned (as in the flip
      of a coin) to 1 of 2 study groups. This is done because no one knows if one study group is
      better, the same, or worse than the other group. You will have an equal chance (50/50) of
      being assigned to either group:

        -  If you are assigned to Group 2A, you will continue to receive apalutamide, abiraterone,
           and prednisone alone.

        -  If you are assigned to Group 2B, you will receive apalutamide, abiraterone, prednisone,
           and ipilimumab.

      If you are found to be eligible for Group 3, you will receive apalutamide, abiraterone, and
      prednisone, plus cabazitaxel and carboplatin.

      Study Drug Administration:

      Each study cycle is 21 days.

        -  You will take 4 tablets of abiraterone acetate and 4 tablets of apalutamide by mouth
           every day while you are on study. The tablets should be taken at the same time every
           day. You will take all of these drugs throughout the entire study.

        -  You should not eat or drink anything except water from 2 hours before your dose until 1
           hour after your dose.

        -  You will also take 1 tablet of prednisone by mouth 2 times every day while you are on
           study. Prednisone should be taken with food.

      The study drug bottle will also include a small packet (called a desiccant) that is placed
      in the bottle to protect the study drug. Do not eat or remove the desiccant. You should
      store your study drug in the study bottle and not place your pills in a separate container,
      such as a pill container.

      If you are assigned to Group 2B, you will also receive ipilimumab by vein over 90 minutes on
      Day 1 of Cycles 4, 5, 6, and 7.

      If you are assigned to Group 3, you will receive cabazitaxel and carboplatin by vein on Day
      1 of Cycles 4, 5, 6, and 7. You will receive cabazitaxel by vein over 60 minutes and then
      receive carboplatin, also by vein, over 60 minutes.

      Study Visits:

      On Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, and 10, then every 2 cycles after that for one
      year, then every 4 cycles after that:

        -  You will have a physical exam.

        -  Blood (about 3 teaspoons) will be drawn for routine tests, for tests of your liver
           function, and to measure your PSA levels.

      Every 2 weeks for the first 9 weeks (Cycles 1-3) and every week of Cycles 4-7, blood (about
      3-4 teaspoons) will be drawn for routine tests and to check your thyroid (Cycle 1 only).

      At Week 3 of Cycle 3:

        -  You will have a physical exam.

        -  Blood (about 3 teaspoons) will be drawn for routine tests, for tests of your liver
           function, and to measure your PSA levels.

        -  You will have a bone scan and either a CT scan or MRI of your abdomen and pelvis. If
           the doctor thinks it is needed, you will also have a chest CT scan.

        -  Blood (about 3 teaspoons) and urine will be collected for biomarker testing.

        -  A bone marrow biopsy and aspiration will be collected for biomarker testing.

      If you are in Group 2B, on Day 1 of Cycles 4, 5, 6, 7 and 8, blood (about 1 teaspoon) will
      be drawn to test your thyroid and adrenal function.

      If you are in Group 2A, on Day 1 of Cycle 8:

        -  Blood (about 3 teaspoons) will be drawn for biomarker testing.

        -  A bone marrow biopsy and aspiration will be collected for biomarker testing.

      If you are in Group 2B, about 3 weeks after your last dose of ipilimumab:

        -  Blood (about 3 teaspoons) will be drawn for biomarker testing

        -  A bone marrow biopsy and aspiration will be collected for biomarker testing.

      If you are in Group 3, about 3 weeks after your last dose of cabazitaxel and carboplatin:

        -  Blood (about 3 teaspoons) will be drawn for biomarker testing.

        -  A bone marrow biopsy and aspiration will be collected for biomarker testing.

      If you are in Group 2A or 2B, at Weeks 21, 33, 45, and every 16 weeks after that:

        -  You will have a bone scan, and either a CT scan or MRI of your abdomen and pelvis. If
           the doctor thinks it is needed, you will also have a chest CT scan.

        -  Blood (about 3 teaspoons) and urine will be collected for biomarker testing.

      If you are in Group 3, at Weeks 15, 21, 33, 45, 57, and every 16 weeks after that:

        -  You will have a bone scan, and either a CT scan or MRI of your abdomen and pelvis. If
           the doctor thinks it is needed, you will also have a chest CT scan.

        -  Blood (about 3 teaspoons) and urine will be collected for biomarker testing.

      If the study doctor thinks it is needed, you may have additional bone scans or CT scans or
      MRIs of the abdomen, pelvis, or chest to check the status of the disease.

      Length of Treatment:

      You may continue taking the study drugs for as long as the doctor thinks it is in your best
      interest. You may no longer be able to take the study drugs if the disease gets worse, if
      intolerable side effects occur, or if you are unable to follow study directions.

      If the study drug becomes commercially available while you are on study, you may begin to
      receive it off of this study. It is also possible that you will continue to receive the
      study drug as part of an extension study, or from a government-sponsored or private health
      program. It is also possible that you and/or your insurance provider will have to pay for
      drugs after they become commercially available if you and your doctor wish to continue them.
      The study doctor will tell you more if any of these things happen.

      End-of-Treatment Visit:

      About 14 days after your last dose of the study drugs, you will return to the clinic for an
      end-of-treatment visit. At this visit:

        -  You will have a physical exam.

        -  Blood (about 4 teaspoons) and urine will be collected for routine and biomarker
           testing. This blood will also be used to check your liver function, and PSA and
           testosterone levels.

        -  You will have a bone scan and a MRI or CT scan to check the status of the disease.

        -  A bone marrow biopsy and aspiration will be collected for biomarker testing.

      About 30 days after your last dose of the study drug, you will be asked how you are doing.
      If you cannot return to the clinic, one of the study staff members will call you to check on
      you. This call should last about 5-10 minutes.

      Long-Term Follow-Up:

      A member of the study staff will check up on you to ask how you are doing every 6 months
      after your last dose of the study drugs. This could be either a phone call or a review of
      your medical and/or other records. If you are contacted by phone, the call will only last a
      few minutes.

      This is an investigational study. Apalutamide is not FDA approved or commercially available.
      It is currently being used for research purposes only. Prednisone is FDA-approved and
      commercially available as a corticosteroid. Ipilimumab is FDA approved to treat metastatic
      melanoma. Abiraterone acetate, cabazitaxel and carboplatin are FDA-approved and commercially
      available for the treatment of metastatic CRPC. It is considered investigational to give
      this combination of drugs for the treatment of metastatic CRPC.

      The study doctor can explain how the study drugs are designed to work.

      Up to 265 participants will be enrolled in this multicenter study. Up to 265 will take part
      at MD Anderson.
    

Trial Arms

NameTypeDescriptionInterventions
ARN-509 + Abiraterone + PrednisoneExperimentalGroup 1: All participants receive ARN-509, Abiraterone, and Prednisone. Participants take 4 tablets of abiraterone acetate and 8 capsules of ARN-509 by mouth every day while on study. Participants also take 1 tablet of prednisone by mouth 2 times every day while on study. Each study cycle is 21 days. After 8 weeks of receiving treatment, blood drawn for biomarker testing. Result of this biomarker test determines whether participant continues the study in next two groups. Group 2A: Participants continue taking ARN-509, Abiraterone, and Prednisone as they did while in Group 1.
  • Abiraterone acetate
  • Prednisone
  • ARN509
ARN-509 + Abiraterone + Prednisone + IpilimumabExperimentalGroup 2B: Participants take 4 tablets of Abiraterone Acetate and 8 capsules of ARN-509 by mouth every day while on study. Participants also take 1 tablet of Prednisone by mouth 2 times every day while on study. Ipilimumab given by vein Day 1 of Cycles 4, 5, 6, and 7. Each study cycle is 21 days.
  • Abiraterone acetate
  • Prednisone
  • Ipilimumab
ARN-509+Abiraterone+Pred+Cabazitaxel+CarboExperimentalGroup 3: Participants take 4 tablets of Abiraterone Acetate and 8 capsules of ARN-509 by mouth every day while on study. Participants also take 1 tablet of Prednisone by mouth 2 times every day while on study. Participants also receive Cabazitaxel and Carboplatin by vein on Day 1 of Cycles 4, 5, 6, and 7. Each study cycle is 21 days.
  • Abiraterone acetate
  • Prednisone
  • ARN509
  • Cabazitaxel
  • Carboplatin

Eligibility Criteria

        Inclusion Criteria:

          1. Willing and able to provide written informed consent.

          2. Male aged 18 years and above.

          3. Histologically or cytologically confirmed adenocarcinoma of the prostate.

          4. Presence of metastatic disease documented on imaging studies (bone scan, CT and/or
             MRI scans).

          5. Patients must have documented evidence of progressive disease as defined by any of
             the following: a) PSA progression: minimum of 2 rising values (3 measurements)
             obtained a minimum of 7 days apart with the last result being at least >/= 1.0 ng/mL;
             b) New or increasing non-bone disease (RECIST 1.1 criteria); c) Positive bone scan
             with 2 or more new lesions (PCWG3).

          6. Surgically or ongoing medically castrated, with baseline testosterone levels of </=
             50 ng/dL (</= 2.0 nM).

          7. Eastern Cooperative Oncology Group (ECOG) Performance Status of </= 2.

          8. Hemoglobin >/= 9.0 g/dL independent of transfusion and or growth factors within 3
             months prior to enrollment.

          9. Platelet count >/= 100,000/uL independent of transfusion and or growth factors within
             3 months prior to enrollment.

         10. Serum albumin >/= 3.0g/dL.

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

         12. Absolute neutrophil count (ANC) >/= 1,500/mm3.

         13. Calculated creatinine clearance (Cockcroft-Gault Equation) >/= 40 mL/min.

         14. Serum potassium >/= Institutional Lower Limit of Normal (ILLN).

         15. Serum magnesium >/= ILLN.

         16. Serum bilirubin < 1.5 x Institutional Upper Limit of Normal (IULN) (except for
             patients with known Gilbert's disease).

         17. Serum AST or ALT < 2.5 x IULN for patients without liver metastases. For patients
             with liver metastases AST or ALT < 5 x IULN is allowed.

         18. Able to swallow study drugs whole as a tablet/capsule.

         19. Male subject with a female partner of childbearing potential or pregnant must agree
             to use two acceptable methods of contraception and not to donate sperm from time of
             Screening until 3 months after the last dose of study treatments.

         20. Patients must agree to tissue collection for correlative studies (including
             participation in PA13-0291 and PA13-0247 for MD Anderson participants) at the
             specified timepoints.

        Exclusion Criteria:

          1. Any prior treatment with: Ipilimumab

          2. Treatment within 28 days of Cycle1 Day1: Any other systemic therapy for prostate
             cancer (with the exception of LHRH agonists and LHRH antagonists for testosterone
             suppression, and bisphosphonates and RANK-ligand inhibitors for bone metastases which
             are allowed). --Any other investigational product --Any medications listed in
             Appendix H.

          3. Treatment within 12 months of Cycle 1 Day 1 with any Cyp17-lyase inhibitor, any 2nd
             generation AR antagonist (e.g. enzalutamide), cabazitaxel or carboplatin.

          4. Patients treated with any Cyp17-lyase inhibitor, any 2nd generation AR antagonist
             (e.g. enzalutamide), cabazitaxel or carboplatin whose disease progressed while on
             treatment or within 3 months of its discontinuation. Patients who have received any
             of these treatments more than 12 months from study entry and whose disease did not
             progress while on treatment or within 3 months of its discontinuation are allowed on
             study.

          5. Patients whose disease is refractory (defined as evidence of disease progression
             while on drug or within 3 months of its discontinuation) to more than 2 lines of
             chemotherapy. Any number of chemotherapies to which the patient's disease is not
             refractory are allowed, as long as time on treatment did not exceed 6 months (counted
             from day 1 of cycle 1 to day 1 of the last cycle of treatment).

          6. Flutamide (Eulexin) treatment within 4 weeks of Cycle 1, Day 1 and Bicalutamide
             (Casodex) or nilutamide (Nilandron) within 6 weeks of Cycle 1 Day 1 (Exceptions: if
             progression is documented prior to this time interval, or if patient is deemed by the
             treating physician to be highly unlikely to respond to AR inhibitor withdrawal (e.g.
             if PSA did not decline for >/= 3 months in response to AR inhibitor given as a second
             line or later intervention, or if patient has symptoms attributed to disease
             progression) only a 3 day washout prior to Cycle 1, Day 1 will be required for any of
             them.

          7. Radiation therapy for treatment of the primary tumor within 6 weeks of Cycle 1, Day
             1. Patients who have received palliative radiation to a single site and recovered are
             eligible.

          8. Any chronic medical condition requiring a higher dose of corticosteroid than 10mg
             prednisone/prednisolone daily. Use of inhaled, intranasal, intra-articular and
             topical steroids is acceptable, as is a short course (i.e. </= 1 day) of
             corticosteroids to prevent a reaction to the IV contrast used for CT scans.

          9. Active infection (requiring oral or IV antibiotics or antiviral therapy) or other
             medical condition that would make prednisone/prednisolone (corticosteroid) use
             contraindicated. Known history of testing positive for human immunodeficiency virus
             (HIV) or known acquired immunodeficiency syndrome (AIDS).

         10. A malignancy [other than the one treated in this study] which required radiotherapy
             or systemic treatment within the past 5 years, or has a >/= 30% probability of
             recurrence within 24 months (except for non-melanoma skin cancer or Ta urothelial
             carcinomas).

         11. Uncontrolled hypertension (systolic BP >/= 140 mmHg or diastolic BP >/= 90 mmHg).
             Patients with a history of hypertension are allowed provided blood pressure is
             controlled by anti-hypertensive treatment.

         12. Prolonged QTc interval on pre-entry electrocardiogram (>/= 450 msec).

         13. Known active or symptomatic viral hepatitis or chronic liver disease.

         14. Clinically significant heart disease as evidenced by myocardial infarction, or
             arterial thrombotic events in the past 6 months, severe or unstable angina, history
             of clinically significant ventricular arrhythmias (such as ventricular tachycardia,
             ventricular fibrillation, or Torsade de pointes), New York Heart Association (NYHA)
             Class III-IV heart disease or cardiac ejection fraction measurement of < 40% at
             baseline.

         15. Autoimmune disease: Patients with a history of inflammatory bowel disease (including
             Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid
             arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic progressive
             sclerosis [scleroderma and variants], Systemic Lupus Erythematosus, autoimmune
             vasculitis [e.g., Wegener's Granulomatosis] or autoimmune neuropathies (such as
             Guillain-Barre syndrome) are excluded from this study. Vitiligo and adequately
             controlled endocrine deficiencies such as hypothyroidism are not exclusionary.

         16. Patients who have had a history of illness which put them at current risk for bowel
             perforation such as acute diverticulitis, intra-abdominal abscess, GI obstruction and
             abdominal carcinomatosis

         17. History of seizure or known condition that may pre-dispose to seizure (including but
             not limited to prior stroke or, loss of consciousness within 1 year prior to
             randomization, brain arteriovenous malformation; or intracranial masses such as
             schwannomas and meningiomas that are causing edema or mass effect).

         18. Gastrointestinal disorder affecting absorption.

         19. Any underlying medical or psychiatric condition, which in the opinion of the
             Investigator, will make the administration of study drug hazardous or obscure the
             interpretation of adverse events.

         20. Untreated symptomatic spinal cord compressions.

         21. Prisoners or subjects who are involuntarily incarcerated.

         22. Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (eg, infectious disease) illness.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Survival (OS) of Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) to the Bone Who Have a Satisfactory Decline in Serum Markers
Time Frame:8 weeks
Safety Issue:
Description:Overall Survival (OS) calculated as the time from trial entry into module 2 or 3 until death or last contact.

Secondary Outcome Measures

Measure:Time to Treatment Failure (TTF) of Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) to the Bone Who Have a Satisfactory Decline in Serum Markers
Time Frame:8 weeks
Safety Issue:
Description:Time to Treatment Failure (TTF) defined as the time from the date of starting combination treatment on Modules 2 (arms 2A and 2B) and Module 3 (arm 3) until the date any one of the following events occurs, whichever comes first: Documented disease progression Death in absence of progression Treatment termination due to toxicity Start of a new therapy in the absence of progression or toxicity.
Measure:Time to Treatment Failure (TTF) of Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) to the Bone Who Have a Unsatisfactory Decline in Serum Markers
Time Frame:8 weeks
Safety Issue:
Description:Time to Treatment Failure (TTF) defined as the time from the date of starting combination treatment on Modules 2 (arms 2A and 2B) and Module 3 (arm 3) until the date any one of the following events occurs, whichever comes first: Documented disease progression Death in absence of progression Treatment termination due to toxicity Start of a new therapy in the absence of progression or toxicity.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Prostate cancer
  • Metastatic castration-resistant prostate cancer to the bone
  • mCRPC
  • Adenocarcinoma of the prostate
  • Biomarkers
  • Abiraterone Acetate
  • Zytiga
  • Prednisone
  • ARN509
  • Ipilimumab
  • Yervoy
  • BMS-734016
  • MDX010
  • Cabazitaxel
  • Jevtana
  • Carboplatin
  • Paraplatin

Last Updated

March 31, 2017