Clinical Trials /

A Salvage Trial of AR Inhibition With ADT and Apalutamide With Radiation Therapy Followed by Docetaxel in Men With PSA Recurrent Prostate Cancer After Radical Prostatectomy (STARTAR)

NCT03311555

Description:

The purpose of this study is to describe the rate of 3-year progression free survival in men with recurrent PSA-only disease after prostatectomy, who receive combined apalutamide (ARN-509) and standard ADT with salvage radiation therapy followed by docetaxel, ADT, and apalutamide, AND who have had testosterone recovery to >100 ng/dl at 36 months. The hypothesis is that AR inhibition with apalutamide added to standard salvage external beam radiation with androgen deprivation therapy, as well as the addition of 6 cycles of docetaxel, will further prolong progression free survival.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Salvage Trial of AR Inhibition With ADT and Apalutamide With Radiation Therapy Followed by Docetaxel in Men With PSA Recurrent Prostate Cancer After Radical Prostatectomy (STARTAR)
  • Official Title: A Salvage Trial of AR Inhibition With ADT and Apalutamide With Radiation Therapy Followed by Docetaxel in Men With PSA Recurrent Prostate Cancer After Radical Prostatectomy (STARTAR)

Clinical Trial IDs

  • ORG STUDY ID: Pro00080868
  • NCT ID: NCT03311555

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
ApalutamideARN-509, JNJ-56021927Recurrent PSA-only non-metastatic prostate cancer
Androgen deprivationRecurrent PSA-only non-metastatic prostate cancer
DocetaxelRecurrent PSA-only non-metastatic prostate cancer

Purpose

The purpose of this study is to describe the rate of 3-year progression free survival in men with recurrent PSA-only disease after prostatectomy, who receive combined apalutamide (ARN-509) and standard ADT with salvage radiation therapy followed by docetaxel, ADT, and apalutamide, AND who have had testosterone recovery to >100 ng/dl at 36 months. The hypothesis is that AR inhibition with apalutamide added to standard salvage external beam radiation with androgen deprivation therapy, as well as the addition of 6 cycles of docetaxel, will further prolong progression free survival.

Trial Arms

NameTypeDescriptionInterventions
Recurrent PSA-only non-metastatic prostate cancerExperimentalSubjects with recurrent PSA-only prostate cancer within 4 years of prostatectomy, and a PSA of greater than 0.2 ng/mL and less than 4 ng/mL in the absence of metastatic disease on CT and bone scans.
  • Apalutamide
  • Androgen deprivation
  • Docetaxel

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically-confirmed diagnosis of prostate adenocarcinoma. Variants of prostate
             cancer, including neuroendocrine features and small cell carcinoma of the prostate,
             are not permitted.

          2. Gleason sum of 7 (with pT3 disease or positive margins or positive nodes [4 or
             fewer]), 8, 9, or 10 based on the radical prostatectomy specimen

          3. PSA relapse within 4 years of prostatectomy defined by persistently detectable or
             rising PSA after surgery.

          4. Evidence of disease recurrence or progression as evidenced by a PSA > 0.20. This
             requires 2 consecutive rises in PSA, at least 1 week apart, over the
             post-prostatectomy nadir OR one PSA value above 0.20 ng/mL IF the patient failed to
             achieve a post-prostatectomy nadir of < 0.2 ng/mL.

          5. Age ≥ 18 years

          6. Karnofsky performance status ≥ 80

          7. Adequate laboratory parameters

               -  Adequate bone marrow function: ANC ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hb
                  >9g/dL

               -  AST/SGOT and ALT/SGPT ≤ 2.5 x Institutional Upper Limit of Normal (ULN)

               -  Serum bilirubin ≤ 1.5 x Institutional ULN (In subjects with Gilbert's syndrome,
                  if total bilirubin is > 1.5xULN, measure direct and indirect bilirubin and
                  patient is eligible if direct bilirubin ≤ 1.5xULN).

               -  Glomerular filtration rate (either estimated or calculated from 24-hour urine
                  collection) ≥ 45 mL/min

               -  Serum potassium ≥3.5 mmol/L

          8. A minimum of 4 weeks from any major surgery prior to Cycle 1 Day 1.

          9. Ability to swallow, retain, and absorb oral medication.

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

         11. Must use a condom if having sex with a pregnant woman.

         12. Male patient and his female partner who is of childbearing potential must use 2
             acceptable methods of birth control (one of which must include a condom as a barrier
             method of contraception) starting at screening and continuing throughout the study
             period and for 3 months after final study drug administration.

        Exclusion Criteria:

          1. Radiographic evidence of metastatic disease. Patients with node-positive disease (≤4
             positive nodes) at the time of radical prostatectomy are eligible. Patients with
             pelvic nodes less than 1.5 cm by short axis at the time of screening are eligible.
             Patients with any enlarged lymph nodes in the retroperitoneum or above the aortic
             bifurcation or with pelvic nodes ≥ 1.5 cm must be excluded.

          2. PSA ≥ 4.0 ng/mL.

          3. Testosterone level ≤ 100 ng/dL.

          4. More than 1 month of prior hormone exposure or hormone exposure within 30 days of
             enrollment (up to 1 month of prior LHRH agonist and/or anti-androgen therapy as
             neoadjuvant therapy prior to prostatectomy is allowed). Prior enzalutamide,
             apalutamide, ketoconazole, abiraterone, or TAK700 for prostate cancer are prohibited.
             Prior antiandrogen therapy (including but not limited to bicalutamide, flutamide,
             nilutamide, enzalutamide, and apalutamide) and prior estrogen therapy (including
             estrogen patch) are not allowed. All investigational agents are prohibited within 30
             days of enrollment.

          5. The following medications are prohibited within 2 weeks of enrollment and while on
             study drug:

               -  5 α-reductase inhibitors (finasteride, dutasteride);

               -  Biologic or other agents with anti-tumor activity against prostate cancer;

               -  Systemic glucocorticoids greater than the equivalent of 10 mg per day of
                  prednisone; oPremedication with systemic glucocorticoids greater than the
                  equivalent of 10 mg per day of prednisone is permitted prior to docetaxel
                  infusions.

               -  Androgens (testosterone, dihydroepiandrosterone [DHEA], etc.)

          6. Prior immunotherapy including sipuleucel-T.

          7. Prior systemic chemotherapy (docetaxel, cabazitaxel, estramustine, other cytotoxic
             agents)

          8. History of solid organ or stem cell transplantation.

          9. History of seizure or any condition that may predispose to seizure (e.g., prior
             cortical stroke, prior head or traumatic brain injury with loss of consciousness,
             prior or current space-occupying lesion in the brain). Also, history of loss of
             consciousness or transient ischemic attack within 12 months of Day 1 visit.

         10. Known or suspected brain metastasis or active leptomeningeal disease.

         11. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,
             active or uncontrolled infection) that could cause unacceptable safety risks or
             compromise compliance with the protocol.

         12. Severe or unstable angina, myocardial infarction, symptomatic congestive heart
             failure, arterial or venous thromboembolic events (eg, pulmonary embolism,
             cerebrovascular accident including transient ischemic attacks), or clinically
             significant ventricular arrhythmias within 6 months prior to enrollment

         13. Sustained uncontrolled hypertension (>150/90 average over 1 week) despite optimal
             medical management

         14. Impairment of gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of apalutamide or increase the risk of radiation (e.g.,
             uncontrolled nausea, vomiting, diarrhea, malabsorption syndromes, prior small bowel
             resection, or inflammatory bowel disease).

         15. Patients who have received prior prostate or pelvic radiotherapy, including external
             beam or brachytherapy.

         16. Patients who have not recovered from side effects of prior systemic therapy prior to
             Cycle 1 Day 1.

         17. Use of medications known to lower the seizure threshold within 4 weeks prior to study
             entry.

         18. Patients unable or unwilling to abide by the study protocol or cooperate fully with
             the investigator.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) at 36 months (3 years)
Time Frame:36 months
Safety Issue:
Description:The proportion of subjects with testosterone >100 ng/dl at 36 months post-Cycle 1 Day 1 without one or more of the following: Serum PSA value of 0.2 ng/mL or more above the post-radiotherapy PSA nadir and confirmed (at least) 4 weeks later by a second PSA measurement higher than the first by any amount Continued rise in the PSA level following study treatment if no nadir is experienced, defined as 2 rising values greater than the baseline PSA and separated by at least 4 weeks Evidence of clinical progression or initiation of systemic therapy for progressive disease Death

Secondary Outcome Measures

Measure:Proportion of subjects with a PSA of <0.1 ng/mL and testosterone recovery
Time Frame:12 months
Safety Issue:
Description:Proportion of subjects with a PSA of <0.1 ng/mL and testosterone recovery (defined as testosterone >100 ng/dl) at 12 months post-Cycle 1 Day 1
Measure:Proportion of subjects with a PSA of <0.1 ng/mL and testosterone recovery
Time Frame:24 months
Safety Issue:
Description:Proportion of subjects with a PSA of <0.1 ng/mL and testosterone recovery (defined as testosterone >100 ng/dl) at 24 months post-Cycle 1 Day 1
Measure:Proportion of subjects with a PSA of <0.1 ng/mL and testosterone recovery
Time Frame:36 months
Safety Issue:
Description:Proportion of subjects with a PSA of <0.1 ng/mL and testosterone recovery (defined as testosterone >100 ng/dl) at 36 months post-Cycle 1 Day 1
Measure:Biochemical progression-free survival
Time Frame:36 months
Safety Issue:
Description:Proportion of subjects still alive without disease progression based on PSA only
Measure:Median PSA nadir value
Time Frame:36 months
Safety Issue:
Description:Median PSA nadir value
Measure:Time to Testosterone recovery
Time Frame:up to 36 months
Safety Issue:
Description:Time to testosterone recovery (defined as testosterone >100 ng/dl)
Measure:Percent of subjects with Adverse Events as assessed by CTCAE v4.0
Time Frame:up to 36 months
Safety Issue:
Description:To describe the safety, feasibility and tolerability profile of combination apalutamide, ADT, and radiation therapy followed by apalutamide, ADT, and docetaxel as assessed by NCI common toxicity scales
Measure:Percentage of patients completing all treatments
Time Frame:36 weeks
Safety Issue:
Description:To describe the percentage of patients completing all treatments including salvage radiation therapy and 6 cycles of docetaxel

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tian Zhang, MD

Trial Keywords

  • Recurrent PSA-only prostate cancer following prostatectomy

Last Updated

October 16, 2019