Clinical Trials /

Multi-arm Multi-modality Therapy for Very High Risk Localized and Low Volume Metastatic Prostatic Adenocarcinoma

NCT03436654

Description:

The purpose of this study is to test if treatment with medications that reduce the male hormone level in the participant's body for a few months before surgery can shrink prostate cancer as much as possible, which might reduce the chances of the cancer coming back in the future. These treatments include a hormone injection given monthly or every three months and the study drugs, which include abiraterone acetate, prednisone, and apalutamide. These medications are being used in combination with surgery and maybe radiotherapy because studies have shown that any single approach on its own is not sufficient to control or get rid of the cancer especially if they have high risk or aggressive features. The researchers hope to learn if combining the study drugs with surgery and radiation will get rid of the cancer from participants' prostates and reduce their prostate-specific antigen (PSA) to an undetectable level.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Multi-arm Multi-modality Therapy for Very High Risk Localized and Low Volume Metastatic Prostatic Adenocarcinoma
  • Official Title: Multi-arm Multi-modality Therapy for Very High Risk Localized and Low Volume Metastatic Prostatic Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: 17-646
  • SECONDARY ID: PCCTC #: c16-183
  • NCT ID: NCT03436654

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
ApalutamideARN-509, ERLEADA™ADT + Apalutamide
Abiraterone AcetateZYTIGAADT + Apalutamide + Abiraterone Acetate + Prednisone
PrednisoneADT + Apalutamide + Abiraterone Acetate + Prednisone
GnRH agonist/antagonistADT + Apalutamide

Purpose

The purpose of this study is to test if treatment with medications that reduce the male hormone level in the participant's body for a few months before surgery can shrink prostate cancer as much as possible, which might reduce the chances of the cancer coming back in the future. These treatments include a hormone injection given monthly or every three months and the study drugs, which include abiraterone acetate, prednisone, and apalutamide. These medications are being used in combination with surgery and maybe radiotherapy because studies have shown that any single approach on its own is not sufficient to control or get rid of the cancer especially if they have high risk or aggressive features. The researchers hope to learn if combining the study drugs with surgery and radiation will get rid of the cancer from participants' prostates and reduce their prostate-specific antigen (PSA) to an undetectable level.

Trial Arms

NameTypeDescriptionInterventions
ADT + ApalutamideExperimental
  • Apalutamide
  • GnRH agonist/antagonist
ADT + Apalutamide + Abiraterone Acetate + PrednisoneExperimental
  • Apalutamide
  • Abiraterone Acetate
  • Prednisone
  • GnRH agonist/antagonist

Eligibility Criteria

        Inclusion Criteria:

          -  Willing and able to provide written informed consent and Authorization for Use and
             Release of Health and Research Study Information (HIPAA authorization) NOTE: HIPAA
             authorization may be either included in the informed consent or obtained separately

          -  Male aged 18 years and above

          -  Serum testosterone of ≥150 ng/dL (For cohorts A and B1, testosterone level requirement
             is exempted if they are already on ADT prior to treatment start. For cohort B2,
             patients will be considered eligible if their testosterone is currently ≥150 ng/dl).

          -  Histologically confirmed adenocarcinoma of the prostate, who meet the following
             criteria:

        Cohort A

          -  Clinically localized disease with histologically confirmed adenocarcinoma of the
             prostate with either ≥3 positive cores or 2 positive cores if >1cm in length with at
             least 50% tumor content WITH

          -  With Gleason score 8-10 OR

          -  Gleason 4+3 with one of the following features:

          -  PSA ≥ 20 mg/mL within 2 months prior to diagnostic biopsy

          -  MRI suspicious for radiographic ≥T3 disease (as long as urologist deems tumor is
             resectable at baseline); defined as >75% probability of extracapsular extension or
             seminal vesicle invasion in the opinion of the reading radiologist.

        OR

          -  Gleason 3+4 or 4+3 and Oncotype DX Genomic Prostate Score of >40

          -  With or without clinical N1 (size >1.5cm in the short axis) (Gleason score requirement
             can be omitted if node positive)

        OR

        Cohort B1

          -  Newly diagnosed low-volume metastatic disease with either.

          -  Bone metastases as documented by CT, MRI or radionuclide bone scan amenable to
             treatment with a maximum of 3 radiation isocenters*

             *(note: patients with PET scans that show osseous metastases that would not be
             amenable to 3-isocenter radiation treatment are still eligible as long as conventional
             imaging shows osseous disease that can be treated with 3 radiation isocenters) And/or

          -  Retroperitoneal nodes up to the level of the renal hilum with/without pelvic nodal
             metastasis ≥1.5cm in the short axis

        OR

        Cohort B2

          -  Rising PSA after RP with:

          -  Osseous or nodal metastases (up to the level of renal hila) as documented by FACBC or
             PSMA PET which are:

          -  amenable to treatment with a maximum of 3 radiation isocenters* These lesions should
             have structural correlates on CT or MRI. Lesions without structural correlates will be
             viewed as equivocal and not need to be irradiated but will be followed.

          -  With associated CT or MRI correlate

          -  No evidence of local recurrence within prior radiation field on MRI or other imaging
             studies i.e. local recurrence is acceptable in patients without prior salvage
             radiation.

          -  Prior salvage radiotherapy is permitted.

             * Multiple lesions within one isocenter may be permitted upon review by the sponsor's
             radiation oncologist;

          -  ECOG performance status of ≤ 1

          -  Adequate bone marrow, hepatic and renal function, as evidenced within 28 days prior to
             treatment start by:

               -  ANC ≥ 1500/µl

               -  Hemoglobin ≥ 9g/dL

               -  Platelet count ≥ 100,000/µl

               -  Serum Creatinine GFR >45 mL/min

               -  Porassium within institutional normal range

               -  Total Bilirubin ≤ 1.5 x ULN (Note: In subjects with Gilbert's syndrome, if total
                  bilirubin is >1.5 x ULN, measure direct and indirect bilirubin and if direct
                  bilirubin is ≤ 1.5 x ULN, subject may be eligible)

               -  Albumin ≥ 3.0 g/dL

               -  SGOT (AST) ≤ 2.5 x ULN

               -  SGPT (ALT) ≤ 2.5 x ULN

          -  Patients must have a clinical T stage documented by the treating urologist/medical
             oncologist within 90 days prior to treatment start using the 7th edition AJCC staging
             system, recorded as the urologist's/medical oncologist's best clinical assessment of
             extent of local disease by digital rectal examination and/or available imaging studies
             such as transrectral ultrasound, CT scan, and/or MRI. Applicable to Cohort A and B1.

          -  The primary tumor must be considered unresectable by RP based on initial imaging with
             gross negative margins as determined by a urologist and documented as such.
             (applicable to cohorts A and B1 only)

          -  Recovery of reversible effects of prior surgery (i.e., incisional pain, wound
             drainage) to Grade ≤1, and at least 4 weeks from prior surgery to treatment start.
             (biopsy excluded)

          -  Able to swallow the study drug(s) whole as a tablet

          -  Willing to take abiraterone acetate on an empty stomach; no food should be consumed at
             least one hour before and for at least two hours after the dose of abiraterone acetate
             is taken (Note: apalutamide does not have to be taken on an empty stomach.)

          -  Agrees 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 agrees 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. Must also agree not to donate
             sperm during the study and for 3 months after receiving the last dose of study drug.

          -  For Cohorts B1 and B2 only, biopsy confirmation of metastases (strongly encouraged; if
             safe and feasible at treating center)

        Exclusion Criteria:

          -  Prior treatment for prostate cancer including prior surgery (excluding TURP and
             patients with rising PSA after RP), pelvic lymph node dissection, radiation therapy
             unless the patient is eligible for Cohort B2.

          -  Prior cytotoxic chemotherapy or biologic therapy for prostate cancer

          -  More than 2 months of prior ADT with GnRH antagonist/agonist at time of treatment
             start. Bicalutamide given for < 2 months at the time of registration as flare
             prevention is allowed. For Cohort B2, prior ADT and/or first generation anti-androgen
             treatment in the (neo)adjuvant and/or salvage setting in conjunction with radiation or
             surgery is allowed provided last effective dose of ADT and/or first generation
             anti-androgen is > 12 months prior to the date of randomization and total duration of
             prior therapy is 12 months or lesser, and their testosterone is currently >150ng/dL.

          -  Prior exposure to ketoconazole (systemic), abiraterone acetate, enzalutamide or other
             agents targeting the AR signaling pathway

          -  Concomitant therapy with any other experimental drug

          -  Known brain, liver, lung or other visceral metastasis (with the exception of
             retroperitoneal and / or pelvic nodal metastases as per inclusion criteria)

          -  Prior prostate cancer metastasis-directed therapies

          -  Currently active second malignancy or past history of malignancies diagnosed within
             the last 5 years that require active therapy and/or in remission with life expectancy
             of < 5 years, with the exception of resected non-melanoma skin cancers, non-muscle
             invasive bladder cancer, state I head and neck cancer, or stage I colorectal cancer

          -  Significant medical condition other than cancer, that would prevent consistent and
             compliant participation in the study that would, in the opinion of the investigator,
             make this protocol unreasonably hazardous including but not limited to:

               -  Any medical condition requiring a higher dose of corticosteroid than 10mg
                  prednisone/prednisolone once daily

               -  History of gastrointestinal disordered (medical disorders or extensive surgery)
                  that may interfere with the absorption of the study agents

               -  Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg);
                  patients with a history of hypertension are allowed provided blood pressure is
                  controlled by anti-hypertensive treatment (systolic BP < 160 mmHg or diastolic BP
                  <95 mmHg)

               -  Active or symptomatic viral hepatitis of chronic liver disease

               -  Known active HIV, Hepatitis B or Hepatitis C infection. (HIV testing is not
                  mandatory)

               -  History of pituitary or adrenal dysfunction

               -  History of hypogonadism

               -  Clinically significant heart disease as evidenced by myocardial infarction, or
                  arterial thrombotic events in the past 6 months, severe or unstable angina, or
                  New York Heart Association (NYHA) Class III or IV heart disease or cardiac
                  ejection fraction measurement of <50% at baseline, or clinically significant
                  ventricular arrhythmias within 6 months prior to treatment start.

               -  History of seizure or any condition that may predispose to seizure (including,
                  but not limited to prior stroke, transient ischemic attack or loss of
                  consciousness </= 1 year prior to treatment start; brain arteriovenous
                  malformation; or intracranial masses such as schawnnomas and meningiomas that are
                  causing edema or mass effect)

               -  Uncontrolled diabetes mellitus

               -  History of inflammatory bowel disease

               -  Baseline moderate and severe hepatic impairment (Child Pugh Class B & C)

          -  Use of any prohibited concomitant medications within 14 days prior to treatment start,
             or use of prohibited concomitant medication listed in section 7.9.1 within the
             outlined windows NOTE: Medications known to lower the seizure threshold must be
             discontinued or substituted at least 4 weeks prior to treatment start

          -  Pre-existing condition that warrants long-term corticosteroid use in excess of 10 mg
             prednisone/prednisolone daily

          -  Known allergies, hypersensitivity or intolerance to apalutamide, abiraterone acetate,
             prednisone, or GBRH agonist or GNRH antagonist

          -  Administration of an investigational therapeutic within 30 days of treatment start

          -  Patients that cannot tolerate MRI

          -  Any condition which, in the opinion of the investigator, would preclude participation
             in this trial
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic complete response
Time Frame:24 months
Safety Issue:
Description:The primary efficacy measure of pathological complete response and minimal residual disease is defined as the less than or equal to 5 mm of morphologically identifiable carcinoma in the RP specimen.

Secondary Outcome Measures

Measure:PSA Response Rate
Time Frame:10 months from randomization
Safety Issue:
Description:defined as percentage of patients with an undetectable PSA at 10 months from randomization (after completion of all protocol treatment)
Measure:Time to PSA Progression
Time Frame:24 months
Safety Issue:
Description:Time from the start of treatment to the date of first evidence of disease progression (serum PSA ≥0.2ng/mL, which is confirmed by a second determination with a PSA ≥0.2 ng/mL, according to the 2007 American Urological Association Prostate Guidelines). This will be estimated by the cumulative incidence function. For each arm, time to PSA progression will be presented for all patients as well as by metastatic status

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • prostate cancer
  • apalutamide
  • abiraterone acetate
  • memorial sloan kettering cancer center
  • 17-646

Last Updated

November 11, 2019