Salvage Therapeutic Radiation With Enzalutamide and ADT in Men With Recurrent Prostate Cancer (STREAM)

NCT02057939 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00049865
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to describe the 2 year progression-free survival in men with recurrent PSA-only disease after prostatectomy receiving combined enzalutamide and standard androgen-deprivation therapy (ADT) with salvage radiation therapy. Eligible men will have recurrent PSA-only prostate cancer within 4 years of prostatectomy, and a PSA of 0.2 - 4 in the absence of metastatic disease on CT and bone scans. In addition to standard ADT and radiation therapy, research participants will take enzalutamide once daily for six months. It is primarily hypothesized the 2 year PFS rate will be improved with the combined therapy compared to the historical control data in a similar patients setting.

Conditions

Prostate Cancer

Keywords

Prostate cancer; enzalutamide; ADT; radiation

Outcome Measures

Primary Outcomes (1)

• Two Year Progression-free Survival

  Percentage of patients surviving 2 years from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of first documented progression or death due to any cause. Progression-free was defined as being without one of the following: serum PSA value of 0.2 ng/mL or more above post-radiotherapy PSA nadir that continues to increase 4 weeks later OR if no nadir is experienced, two rising PSA values over 4 or more weeks OR evidence of clinical progression or initiation of systemic therapy for progressive disease

  2 years

Secondary Outcomes (6)

• PSA Less Than 0.1

  every year, up to 3 years

• Three Year Progression-free Survival

  3 years

• Biochemical Progression-free Survival

  3 years

• PSA Nadir

  8 weeks

• Time to Testosterone Recovery

  3 years

Study Arms (1)

Enzalutamide

EXPERIMENTAL

Enzalutamide, Androgen Deprivation, and Radiation Therapy

Drug: enzalutamide; Drug: Androgen Deprivation; Radiation: Radiation Therapy

Interventions

enzalutamide DRUG

160 mg orally once daily for six months

Also known as: Xtandi

Enzalutamide

Androgen Deprivation DRUG

Two injections each lasting three months, for a total of six months of androgen deprivation therapy. Doctor will help determine which androgen deprivation drug to use.

Also known as: leuprolide acetate (Lupron Depot, 22.5 mg)

Enzalutamide

Radiation Therapy RADIATION

Daily (Monday-Friday) for 6-8 weeks, final dose of approximately 66 Gy

Enzalutamide

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, 8, 9, or 10 at the time of prostatectomy.
• 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 ≥ 70
• 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
• Serum creatinine ≤ 1.5 x Institutional ULN or 24-hour clearance ≥ 50 mL/min
• A minimum of 4 weeks from any major surgery prior to registration.
• Ability to swallow, retain, and absorb oral medication.
• Ability to understand and the willingness to sign a written informed consent document.
• Must use a condom if having sex with a pregnant woman.

You may not qualify if:

• Radiographic evidence of metastatic disease. Patients with node-positive disease (\<2 positive nodes) at the time of radical prostatectomy are eligible. Patients with pelvic nodes up to 2 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 ≥ 2 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 registration. Prior enzalutamide, ketoconazole, abiraterone, or TAK700 prohibited. Prior 5α reductase inhibitors are allowed.
• 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.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of enzalutamide or increase the risk of radiation (e.g., uncontrolled nausea, vomiting, diarrhea, malabsorption syndromes, prior small bowel resection, or inflammatory bowel disease).
• Patients who have received prior prostate or pelvic radiotherapy, including external beam or brachytherapy.
• Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy prior to registration.
• Patients unable or unwilling to abide by the study protocol or cooperate fully with the investigator.

Sponsors & Collaborators

• Duke University: lead
• Medivation, Inc.: collaborator
• Astellas Pharma Inc: collaborator

Study Sites (3)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (1)

• Bitting RL, Healy P, George DJ, Anand M, Kim S, Mayer T, Winters C, Riggan C, Rasmussen J, Wilder R, Stein M, Frizzell B, Harrison MR, Zhang T, Lee WR, Wu Y, Koontz BF, Armstrong AJ. Phase II Trial of Enzalutamide and Androgen Deprivation Therapy with Salvage Radiation in Men with High-risk Prostate-specific Antigen Recurrent Prostate Cancer: The STREAM Trial. Eur Urol Oncol. 2021 Dec;4(6):948-954. doi: 10.1016/j.euo.2020.01.005. Epub 2020 Feb 13.

  PMID: 32063492 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

enzalutamide; Leuprolide; Radiotherapy

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

Results Point of Contact

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

andrew.armstrong@duke.edu

919-668-4615

Study Officials

• Andrew Armstrong, MD ScM FACP

  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

Study Record Dates

• First Submitted: January 31, 2014
• First Posted: February 7, 2014
• Study Start: April 1, 2014
• Primary Completion: March 2, 2018
• Study Completion: June 5, 2019
• Last Updated: June 26, 2019
• Results First Posted: March 20, 2019

Record last verified: 2019-06

Locations

US (3)