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Castration Levels of TestosteronePhase 2NCT02703623

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

A Phase 2 study testing Abiraterone Acetate, Apalutamide and Cabazitaxel in people with Castration Levels of Testosterone and Castration-Resistant Prostate Carcinoma, run by M.D. Anderson Cancer Center at 3 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Abiraterone Acetate, Apalutamide and Cabazitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
196 participants
Where
3 sitesUnited States
Study dates
18 May 2016to 31 Mar 2028
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Each patient must meet the following criteria to be enrolled in this study:
  • Willing and able to provide written informed consent.
  • Male aged 18 years and above.
  • Histologically or cytologically confirmed adenocarcinoma of the prostate.
  • Presence of metastatic disease documented on imaging studies (bone scan, CT and/or MRI scans).
  • 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).
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  • Surgically or ongoing medically castrated, with baseline testosterone levels of ≤ 50 ng/dL (≤ 2.0 nM).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2.
  • Hemoglobin ≥ 7.5 g/dL in the presence of bone marrow involvement independent of transfusion and/or growth factors within 3 months prior to enrollment.
  • Platelet count ≥100,000/μL independent of transfusion and/or growth factors within 3 months prior to enrollment.
  • Serum albumin ≥3.0g/dL.
  • Medications known to lower the seizure threshold (see Appendix H under prohibited medications) must be discontinued or substituted at least 4 weeks prior to study entry.
  • Absolute neutrophil count (ANC) ≥ 1,500/mm3
  • Calculated creatinine clearance (Cockcroft-Gault Equation) ≥ 40 mL/min.
  • Serum potassium ≥ Institutional Lower Limit of Normal (ILLN).
  • Serum magnesium ≥ ILLN.
  • Serum bilirubin < 1.5 x Institutional Upper Limit of Normal (IULN) (except for patients with known Gilbert's disease).
  • 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.
  • Able to swallow study drugs whole as a tablet/capsule.
  • 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 as per Section 5.7. 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. (Additional details in Section 5.5.1.1).

Who cannot join

  • Patients who meet any of the following criteria will be excluded from the study:
  • Prior or Concurrent Treatments:
  • Any prior treatment with:
  • Ipilimumab
  • 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 Sipuleucel-T, and bisphosphonates and RANK-ligand inhibitors for bone metastases which are allowed).
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  • Any other investigational product.
  • Any medications listed in Appendix H
  • Treatment within 12 months of Cycle 1 Day 1 with any Cyp17-lyase inhibitor, any 2 nd generation AR antagonist (e.g. enzalutamide), cabazitaxel orcarboplatin.
  • 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).
  • 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).
  • 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 attributable to disease progression) only a 3 day washout prior to Cycle 1, Day 1 will be required for any of them.
  • Radiation therapy for treatment of the primary tumor within 6 weeks of Cycle 1, Day 1. Patients who have received palliative radiation and recovered areeligible.
  • Any chronic medical condition requiring a higher dose of corticosteroid than 10mg prednisone/prednisolone daily. Use of inhaled, intranasal, intra-articular and topical steroids are acceptable, as is a short course (i.e. ≤ 1 day) of corticosteroids to prevent a reaction to the IV contrast used for CT scans.
  • Concurrent illnesses:
  • 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).
  • 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).
  • 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.
  • Prolonged QTc interval on pre-entry electrocardiogram (≥ 450 msec).
  • Known active or symptomatic viral hepatitis or chronic liver disease.
  • 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.
  • 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.
  • 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.
  • 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).
  • Gastrointestinal disorder affecting absorption. 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.
  • Untreated symptomatic spinal cord compressions.
  • Other:
  • Prisoners or subjects who are involuntarily incarcerated.
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • MD Anderson in Katy

    Houston, Texas, 77094

  • MD Anderson in Sugar Land

    Sugar Land, Texas, 77478

Other trials in United States

About this study

Official title: A Dynamic Allocation Modular Sequential Trial of Approved and Promising Therapies in Men With Metastatic Castrate Resistant Prostate Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the overall survival (OS) of men with metastatic castration-resistant prostate cancer (mCRPC) who have SATISFACTORY features after to 8 weeks of maximal androgen receptor (AR)-inhibitory therapy and receive treatment with abiraterone acetate, prednisone and apalutamide plus or minus ipilimumab.

II. To estimate the OS of men with mCRPC who have UNSATISFACTORY features after to up to 8 weeks of maximal androgen receptor (AR)-inhibitory therapy and receive treatment with abiraterone acetate, prednisone, apalutamide, cabazitaxel and carboplatin.

III. To determine the TOXICITY PROFILE of the following combinations in men with mCRPC:

IIIa. Abiraterone acetate, prednisone, apalutamide. IIIb. Abiraterone acetate, prednisone, apalutamide and ipilimumab. IIIc. Abiraterone acetate, prednisone, apalutamide, cabazitaxel and carboplatin.

IV. To determine whether the BASELINE "AR RESPONSE SIGNATURE" correlates with SATISFACTORY or UNSATISFACTORY features after up to 8-weeks of treatment with abiraterone, prednisone and apalutamide.

SECONDARY OBJECTIVES:

  1. To "pick the winner" in terms of time to treatment failure (TTF) between the following two combinations, in men with mCRPC and satisfactory features after 8 weeks of maximal AR-inhibitory therapy:

Ia. Abiraterone acetate, prednisone, apalutamide. Ib. Abiraterone acetate, prednisone, apalutamide and ipilimumab. II. To determine the TTF in men with mCRPC and unsatisfactory features after up to 8 weeks of maximal AR-inhibitory therapy ted with abiraterone acetate, prednisone, apalutamide, cabazitaxel and carboplatin.

III. To determine whether the "baseline AR response signature" predicts for benefit by prognostic grouping (satisfactory/unsatisfactory) and treatment arm.

IV. To investigate therapy-specific marker signatures (immune based, bone based and anaplastic) and their link to outcome.

  1. To collect and archive bone marrow biopsy, bone marrow aspirate, serum, plasma, and tissue samples in study patients for later hypothesis generating associations.

OUTLINE: After an 8-week lead-in phase, patients with satisfactory decline in serum markers are randomized to 1 of 2 arms (Arm 2A or 2B), and patients with unsatisfactory decline in serum markers are assigned to Arm 3.

LEAD-IN PHASE: Patients receive abiraterone acetate orally (PO) daily, prednisone PO twice daily (BID), and apalutamide PO daily for 8 weeks in the absence of disease progression or unexpected toxicity.

ARM 2A: Patients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily in the absence of disease progression or unexpected toxicity.

ARM 2B: Patients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Patients also receive ipilimumab intravenously (IV) over 90 minutes on day 1 of courses 4-7. Courses repeat every 3 weeks in the absence of disease progression or unexpected toxicity.

ARM 3: Patients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Patients also receive cabazitaxel IV over 60 minutes and carboplatin IV over 60 minutes on day 1 of courses 4-13. Courses repeat every 3 weeks in the absence of disease progression or unexpected toxicity.

After completion of study treatment, patients are followed up at 14 and 30 days, and then every 6 months thereafter.

Being tested
Abiraterone Acetate, Apalutamide, Cabazitaxel, Carboplatin, Ipilimumab
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Abiraterone AcetateDrug

    Also called CB7630, Zytiga

    Given PO

  • ApalutamideDrug

    Also called ARN 509, ARN-509, ARN509, JNJ 56021927

    Given PO

  • CabazitaxelDrug

    Also called Jevtana, RPR-116258A, Taxoid XRP6258, XRP-6258

    Given IV

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PrednisoneDrug

    Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl

    Given PO

Study groups in NCT02703623
Study groupRoleWhat they receive
Arm 2A (abiraterone acetate, prednisone, apalutamide)ExperimentalPatients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily in the absence of disease progression or unexpected toxicity.
Receives: Drug: Abiraterone Acetate; Drug: Apalutamide; Other: Laboratory Biomarker Analysis; Drug: Prednisone
Arm 2B (abiraterone acetate, prednisone, ARN-509, ipilimumab)ExperimentalPatients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Patients also receive ipilimumab IV over 90 minutes on day 1 of courses 4-7. Courses repeat every 3 weeks in the absence of disease progression or unexpected toxicity.
Receives: Drug: Abiraterone Acetate; Drug: Apalutamide; Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Drug: Prednisone
Arm 3(abiraterone, prednisone, ARN509,cabazitaxel,carboplatin)Active comparatorPatients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Patients also receive cabazitaxel IV over 60 minutes and carboplatin IV, over 60 minutes on day 1 of courses 4-13. Courses repeat every 3 weeks in the absence of disease progression or unexpected toxicity.
Receives: Drug: Abiraterone Acetate; Drug: Apalutamide; Drug: Cabazitaxel; Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival (OS)

    Will be reported for each arm. Estimated by Bayesian posterior estimates along with the 95% credible intervals and presented using Kaplan-Meier curves.

    Measured: Up to 4 years

  2. Incidence of adverse events as measured by the method of Thall et al

    Will be reported overall as well as by grade and attribution to study drug for each arm.

    Measured: Up to 4 years

  3. Androgen receptor (AR) response marker signature

    Chi-Square tests or chi-square exact tests at a two-sided significance level of 0.05 will be used to evaluate the association between "AR-response marker signatures" (good/bad) and the "allocation serum marker decline" (satisfactory/unsatisfactory).

    Measured: At baseline

  4. Allocation serum marker decline

    Serum levels of prostate specific antigen (PSA) and circulating tumor cells (CTCs) will be evaluated and correlated with AR response marker signatures. Chi-Square tests or chi-square exact tests at a two-sided significance level of 0.05 will be used to evaluate the association between "AR-response marker signatures" (good/bad) and the "allocation serum marker decline" (satisfactory/unsatisfactory). Multivariate logistic regression analysis adjusting for the effects of other baseline factors will also be used to identify factors associated with a satisfactory allocation serum marker profile.

    Measured: At 8 weeks

Secondary outcomes (1)

  1. Time to treatment failure (TTF)

    Estimated by Bayesian posterior estimates along with the 95% credible intervals and presented using Kaplan-Meier curves.

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Mar 2016 (estimated)
  2. Study start18 May 2016
  3. Primary completion31 Mar 2028 (estimated)
  4. Study completion31 Mar 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
196 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02703623
Sponsor's protocol ID
2014-0386
Other IDs
NCI-2016-00670, 2014-0386
Status last verified
Sep 2026
First submitted
4 Mar 2016
Last updated
14 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

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