Androgen Deprivation Therapy and Apalutamide With or Without Radiation Therapy for the Treatment of Biochemically Recurrent Prostate Cancer, RESTART Study

NCT04585932 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: 2019-1093NCI-2020-02553
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well androgen deprivation therapy and apalutamide with or without radiation therapy works for the treatment of prostate cancer that has a rise in the blood level of prostate-specific antigen (PSA) and has come back after treatment with surgery or radiation (biochemically recurrent). Androgens can cause the growth of prostate tumor cells. Apalutamide may help fight prostate cancer by blocking the use of androgens by the tumor cells. Androgen deprivation therapy drugs, leuprolide or degarelix, work to lower the amount of androgen in the body, also preventing the tumor cells from growing. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radiation therapy with apalutamide and androgen deprivation therapy may help to control prostate cancer that has come back in only a few (up to 5) spots in the body.

Conditions

Biochemically Recurrent Prostate Carcinoma; Metastatic Prostate Carcinoma; Oligometastatic Prostate Carcinoma; Stage IV Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Time to prostate specific antigen (PSA) recurrence

  Will estimate with the 95% Bayesian credible interval.

  From treatment start with androgen deprivation therapy plus apalutamide until PSA recurrence (> 0.2 ng/ml) for patients who received surgery, or PSA >= nadir+2ng/mL for patients who received only prior definitive radiation of the prostate, up to 4 years

Secondary Outcomes (14)

• Time to testosterone recovery

  From treatment start until testosterone > 150ng/dL, assessed up to 4 years

• Eugonadal time to PSA recurrence

  Up to 4 years

• Overall survival

  Up to 4 years

• Incidence of adverse events

  Up to 4 weeks after last dose of apalutamide

• Time to first new metastasis or local/pelvic recurrence

  Up to 4 years

Other Outcomes (1)

• Identification of response or resistance markers

  Up to 4 years

Study Arms (2)

Group I (apalutamide, leuprolide, degarelix)

ACTIVE COMPARATOR

Patients receive apalutamide PO QD on days 1-28 and ADT consisting of leuprolide IM every 12 weeks or degarelix SC every 4 weeks. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Apalutamide; Drug: Degarelix; Drug: Leuprolide Acetate; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Group II (apalutamide, leuprolide, degarelix, RT)

EXPERIMENTAL

Patients receive apalutamide PO QD on days 1-28 and ADT consisting of leuprolide IM every 12 weeks or degarelix SC every 4 weeks. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo RT between cycles 4-7 in the absence of disease progression or unacceptable toxicity.

Drug: Apalutamide; Drug: Degarelix; Drug: Leuprolide Acetate; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radiation Therapy

Interventions

Apalutamide DRUG

Given PO

Also known as: ARN 509, ARN-509, ARN509, Erleada, JNJ 56021927, JNJ-56021927

Group I (apalutamide, leuprolide, degarelix); Group II (apalutamide, leuprolide, degarelix, RT)

Degarelix DRUG

Given SC

Also known as: FE200486, Firmagon

Group I (apalutamide, leuprolide, degarelix); Group II (apalutamide, leuprolide, degarelix, RT)

Leuprolide Acetate DRUG

Given IM

Also known as: A-43818, Abbott 43818, Abbott-43818, Carcinil, Depo-Eligard, Eligard, Enanton, Enantone, Enantone-Gyn, Ginecrin, LEUP, Leuplin, Leuprorelin Acetate, Lucrin, Lucrin Depot, Lupron, Lupron Depot, Lupron Depot-3 Month, Lupron Depot-4 Month, Lupron Depot-Ped, Lutrate, Procren, Procrin, Prostap, TAP-144, Trenantone, Uno-Enantone, Viadur

Group I (apalutamide, leuprolide, degarelix); Group II (apalutamide, leuprolide, degarelix, RT)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Group I (apalutamide, leuprolide, degarelix); Group II (apalutamide, leuprolide, degarelix, RT)

Questionnaire Administration OTHER

Ancillary studies

Group I (apalutamide, leuprolide, degarelix); Group II (apalutamide, leuprolide, degarelix, RT)

Radiation Therapy RADIATION

Undergo RT

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Group II (apalutamide, leuprolide, degarelix, RT)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed prostate cancer
• Signed informed consent form (ICF) indicating that the subject understands the purpose of, and procedures required for, the study and is willing to participate in the study
• Consent to MD Anderson laboratory protocol Lab02-152
• Available tumor tissue sample (recently collected +/- archival)
• Biochemically recurrent prostate cancer following definitive treatment with radical prostatectomy or / and external beam radiation therapy. Patient may have received prior androgen deprivation with or without other treatments in the neoadjuvant, adjuvant or salvage setting as long as \>= 6 months from discontinuation have elapsed at the time of randomization
• Progression based on the following criteria:
• PSA progression: For patients with prior radical prostatectomy (+/- radiation), PSA progression defined by a minimum of two rising PSA levels with an interval of at least 1 week between each determination and a PSA of \>= 0.5 ng/ml at screening. For patients with only prior definitive radiation of the prostate, PSA recurrence is defined as PSA \>= nadir+2 ng/mL
• PSA doubling time of =\< 12 months at the time of study entry. Calculation of PSA doubling time should include the use of all available PSA values obtained within past 12 months prior to randomization, with a minimum of 3 values \>= 0.1 ng/mL PSA values obtained prior to localized therapy will be excluded. PSA doubling time to be estimated using Memorial Sloan Kettering Cancer Center online calculator
• Identification of up to 5 metastatic lesions or/and pelvic node recurrent sites by advanced imaging technology (PSMA PET/CT or fluciclovine PET/CT). In case of inconsistency between the two imaging modalities, up to 5 lesions in the PSMA/PET will be accepted. All sites should be eligible to be treated with definitive intent. At least one of these lesions will be histologically confirmed. Symptomatic metastatic disease or disease impending symptoms (e.g. brain metastasis, painful bone metastasis, and spine disease) can be treated with definitive local therapy prior to enrollment. This lesion will be counted towards the total number of metastatic lesions
• Must be able to receive luteinizing hormone-releasing hormone (LHRH) agonist or antagonist during the course of the study
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1
• Must be able to swallow tablets
• To avoid risk of drug exposure through the ejaculate (even men with vasectomies), patients must agree while on study drug and for 3 months following the last dose of study drug to:
• Use a condom during sexual activity
• Not donate sperm

You may not qualify if:

• Histologically confirmed recurrence in a prior definitively irradiated prostate cancer field per the judgment of the investigator
• Ongoing androgen deprivation therapy (with or without short-term first generation anti-androgens) for \> 4 weeks at the time of randomization
• =\< 30 days prior to cycle 1 day 1, patient had:
• A transfusion (platelets or red blood cells)
• Hematopoietic growth factors
• An investigational agent (=\< 30 days or 5 half-lives, whichever is longer)
• Major surgery
• Active hematologic or solid malignancy other than prostate cancer with at least 30% chance of recurrence per investigator assessment; (exceptions: adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission)
• Known allergies, hypersensitivity, or intolerance to apalutamide or LHRH agonist/antagonist or excipients
• Current evidence of any of the following:
• Uncontrolled hypertension
• Gastrointestinal disorder affecting absorption
• Corrected QT interval by the Fridericia correction formula (QTcF) \> 450 msec on the screening electrocardiogram (ECG)
• History of clinically significant cardiovascular disease including, but not limited to:
• Myocardial infarction or unstable angina =\< 3 months prior to treatment initiation

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; Leuprolide; luprolide acetate gel depot; Radiotherapy; Radiation

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)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Therapeutics; Physical Phenomena

Study Officials

• Eleni Efstathiou

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: October 14, 2020
• Study Start: November 24, 2020
• Primary Completion: January 8, 2021
• Study Completion: January 8, 2021
• Last Updated: January 20, 2021

Record last verified: 2021-01

Locations

US (1)