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 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: Pro00080868
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

Recurrent PSA-only prostate cancer following prostatectomy

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) at 36 Months (3 Years)

  The percentage 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

  up to 36 months

Secondary Outcomes (8)

• Number of Participants With a PSA of <0.1 ng/mL and Testosterone Recovery at 12 Months Post-Cycle 1 Day 1

  12 months

• Percentage of Participants With a PSA of <0.1 ng/mL and Testosterone Recovery at 24 Months Post-Cycle 1 Day 1

  24 months

• Percentage of Participants With a PSA of <0.1 ng/mL and Testosterone Recovery at 36 Months Post-Cycle 1 Day 1

  36 months

• Biochemical Progression-free Survival (PFS) at 36 Months (3 Years)

  36 months

• Median PSA Nadir Value

  36 months

Study Arms (1)

Recurrent PSA-only non-metastatic prostate cancer

EXPERIMENTAL

Subjects 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.

Drug: Apalutamide; Drug: Androgen deprivation; Radiation: Salvage radiation therapy; Drug: Docetaxel

Interventions

Apalutamide DRUG

240mg tablet daily for 36 weeks

Also known as: ARN-509, JNJ-56021927

Recurrent PSA-only non-metastatic prostate cancer

Androgen deprivation DRUG

ADT will consist of treatment with a GnRH agonist or antagonist per physician and institutional preference. Either leuprolide acetate (Lupron Depot, 22.5 mg or 45 mg IM), triptorelin pamoate (Trelstar, 11.25 mg or 22.5 mg IM), goserelin acetate (Zoladex, 10.8mg SC) or degarelix (Firmagon 120 mg or 240 mg SC) will be administered monthly, every 3 months, or every 6 months, depending on institutional standards, for 36 weeks total.

Recurrent PSA-only non-metastatic prostate cancer

Salvage radiation therapy RADIATION

On week 9 (+/- 28 days), subjects will begin salvage radiation therapy to the prostate bed. The total dose to the prostate bed must be 66-74 Gy in 1.8-2 Gy daily fractions over a total of 6-8 weeks

Recurrent PSA-only non-metastatic prostate cancer

Docetaxel DRUG

About 4 weeks (+/- 2 weeks, pending recovery of adverse events from radiation to Grade 2 or less) after completing radiation, patients will start docetaxel 75mg/m2 intravenously, every 3 weeks for 6 cycles.

Recurrent PSA-only non-metastatic prostate cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically-confirmed diagnosis of prostate adenocarcinoma. Variants of prostate cancer, including neuroendocrine features and small cell carcinoma of the prostate, are not permitted.
• 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
• PSA relapse within 4 years of prostatectomy defined by persistently detectable or rising PSA after surgery.
• 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.
• Age ≥ 18 years
• Karnofsky performance status ≥ 80
• 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
• A minimum of 4 weeks from any major surgery prior to Cycle 1 Day 1.
• Ability to swallow, retain, and absorb oral medication.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• 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.
• PSA ≥ 4.0 ng/mL.
• Testosterone level ≤ 100 ng/dL.
• 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.
• The following medications are prohibited within 2 weeks of enrollment and while on study drug:
• 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.)
• Prior immunotherapy including sipuleucel-T.
• Prior systemic chemotherapy (docetaxel, cabazitaxel, estramustine, other cytotoxic agents)
• History of solid organ or stem cell transplantation.
• 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.
• Known or suspected brain metastasis or active leptomeningeal disease.
• 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.

Sponsors & Collaborators

• Andrew J. Armstrong, MD: lead

Study Sites (5)

GU Research Network / Urology Cancer Center

Omaha, Nebraska, 68130, United States

Location

Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Duke Cancer Center Cary

Cary, North Carolina, 27518, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest Univesity

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide; Docetaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Andrew Armstrong, MD
• Organization: Duke University

andrew.armstrong@duke.edu

919-668-8797

Study Officials

• Tian Zhang, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine and Surgery

Study Record Dates

• First Submitted: September 26, 2017
• First Posted: October 17, 2017
• Study Start: March 28, 2018
• Primary Completion: December 22, 2022
• Study Completion: December 22, 2022
• Last Updated: March 19, 2024
• Results First Posted: March 19, 2024

Record last verified: 2024-02

Locations

US (5)