Genomic Biomarker-Selected Umbrella Neoadjuvant Study for High Risk Localized Prostate Cancer

NCT04812366 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: H20-03434
• Study Type: interventional
• Target: 315
• Locations: 2 countries
• Sites: 9

Brief Summary

The objective of this study is to see if providing an appropriate therapy based on the genomic testing of prostate tumour tissue will result in an improved clinical response. Each participant will be treated with 8 weeks of a luteinizing hormone-releasing hormone agonist (LHRHa) plus apalutamide (APA) while genome sequence characterization is being done. Participants with biopsy specimens deemed unevaluable for genomic testing will remain on LHRHa plus APA for an additional 16 weeks. Participants with evaluable tissue will be assigned to one of the open-label sub-studies on the basis of genomic profiling results. Within each group, they will be randomized to a specific treatment arm either LHRHa plus APA alone or adding abiraterone acetate and prednisone, docetaxel or niraparib. The study will evaluate the response rate and outcomes after radical prostatectomy in each arm of the trial.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Complete Pathologic Response (pCR)

  Pathological Minimal Residual Disease (pMRD): pathological minimal residual disease (pMRD) is defined as residual tumour 5mm or less.

  6 years

• Pathological Minimal Residual Disease (pMRD)

  Pathological minimal residual disease is defined as residual tumour 5 mm or less.

  6 years

Secondary Outcomes (3)

• Pain level assessment

  6 years

• Generic Quality of Life (QoL)

  6 years

• Quality of Life-Prostate Cancer Patients

  6 years

Study Arms (6)

Group 1a

ACTIVE COMPARATOR

LHRHa plus apalutamide.

Drug: Apalutamide 60mg Tab

Group 1b

ACTIVE COMPARATOR

LHRHa plus apalutamide plus abiraterone acetate plus prednisone.

Drug: Apalutamide 60mg Tab; Drug: Abiraterone Acetate 250mg; Drug: Prednisone 5mg Tab

Group 2a

ACTIVE COMPARATOR

LHRHa plus abiraterone acetate plus prednisone.

Drug: Abiraterone Acetate 250mg; Drug: Prednisone 5mg Tab

Group 2b

ACTIVE COMPARATOR

LHRHa plus abiraterone acetate plus prednisone plus docetaxel.

Drug: Abiraterone Acetate 250mg; Drug: Prednisone 5mg Tab; Drug: Docetaxel

Group 3

ACTIVE COMPARATOR

LHRHa plus abiraterone acetate plus prednisone plus niraparib

Drug: Abiraterone Acetate 250mg; Drug: Prednisone 5mg Tab; Drug: Niraparib 100mg Oral Capsule

Group 4

ACTIVE COMPARATOR

LHRHa plus apalutamide plus atezolizumab

Drug: Apalutamide 60mg Tab; Drug: Atezolizumab

Interventions

Apalutamide 60mg Tab DRUG

4 tablets by mouth once a day for 24 weeks

Group 1a; Group 1b; Group 4

Abiraterone Acetate 250mg DRUG

4 tablets by mouth on an empty stomach once a day for 16 weeks

Group 1b; Group 2a; Group 2b; Group 3

Prednisone 5mg Tab DRUG

1 tablet by mouth once daily while taking abiraterone acetate

Group 1b; Group 2a; Group 2b; Group 3

Docetaxel DRUG

Infusion every 3 weeks for 6 cycles (each cycle has 3 weeks)

Group 2b

Niraparib 100mg Oral Capsule DRUG

3 capsules by mouth once daily for 16 weeks

Group 3

Atezolizumab DRUG

1200mg infusion every 3 weeks for 6 cycles

Group 4

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: This is a prostate cancer study
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- I. Males ≥ 18 years of age
• II. Histologically confirmed adenocarcinoma of the prostate without pathologic evidence of small cell differentiation at the time of initial diagnosis
• III. High-risk localized prostate cancer as defined by:
• PSA (prostate specific antigen) \>20, any GS or \>8 or
• Gleason pattern 4 in 6 or more systematic cores (pattern 4 must be dominant, ≥50% average across 6 or more systematic cores) or
• ≥ 50% Gleason pattern 4 in 3 or more systematic or Magnetic Resonance Imaging (MRI)-targeted cores and PSA ≥ 20 (may include G4+3 or G4+4 but pattern 4 must be dominant, ≥50% average across 3 or more systematic cores) or
• ≥25% Gleason pattern 5 in 3 or more systematic or MRI-targeted cores (may include G4+5, or G3+5, but pattern 5 must be ≥25% average across 3 or more systematic cores).
• Gleason \> 8 or greater on minimum of one core either targeted or systematic biopsy and PSA \>20
• Participants with oligometastatic (\< 3) metastases by PSMA (Prostate-Specific Membrane Antigen) imaging only who are deemed candidates for radical prostatectomy are eligible
• IV. Participants must consent to genetic testing at registration and prior to assignment by a central reference laboratory
• V. No prior systemic or localized treatment for prostate cancer. Up to 30 days of LHRHa is allowable prior to treatment.
• VI. ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1 (Appendix II) and a life expectancy of ≥ 3 years
• VII. Participants must have adequate end-organ function and all laboratory tests must be performed within 4 weeks prior to registration into master protocol.
• VIII. Participant consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each participant must sign a consent form prior to enrolment in the trial to document their willingness to participate.

You may not qualify if:

• \- I. Received more than 30 days of LHRHa prior to registration and initiation of LHRHa + APA
• II. Stage T4 prostate cancer by clinical examination or radiologic evaluation
• III. Hypogonadism or severe androgen deficiency as defined by screening serum testosterone more than 50 ng/dL below the normal range for the institution
• IV. Participants with serious illnesses or medical conditions which could cause unacceptable safety risks or would not permit the participant to be managed according to the protocol. This includes but is not limited to:
• Active infection or chronic liver disease requiring systemic therapy;
• Active or known human immunodeficiency virus (HIV) with detectable viral load;
• Uncontrolled or recent clinically significant cardiac disease, including: angina pectoris, symptomatic pericarditis, coronary artery bypass grafting, coronary angioplasty, or stenting, or myocardial infarction in the previous 12 months; history of documented congestive heart failure (New York Heart Association functional classification III-IV) or cardiomyopathy; history of any cardiac arrhythmias, e.g. ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months;
• Participants with uncontrolled hypertension
• V. Participants who are unable to swallow oral medication and/or have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• VI. Participants with a history of hypersensitivity to any of the study drugs or any excipient
• VII. Participants with a history of non-compliance to medical regimen
• VIII. Severe concurrent disease, infection, or co-morbidity that, in the judgement of the Investigator, would make the participant inappropriate for enrollment or prostatectomy
• IX. Prior androgen deprivation, chemotherapy, surgery, or radiation for prostate cancer
• X. Receiving concurrent androgens, estrogens, or pregestational agents, or prior exposure to any of these agents within 6 months prior to randomization
• XI. M1 by conventional imaging (CT, bone scan)

Sponsors & Collaborators

• University of British Columbia: lead
• Janssen Inc.: collaborator
• University Health Network, Toronto: collaborator

Study Sites (9)

University of California Davis

Sacramento, California, 95817, United States

RECRUITING

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

University of Michigan Health

Ann Arbor, Michigan, 48109-5946, United States

RECRUITING

U.T. MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Vancouver Prostate Centre

Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

RECRUITING

Ottawa Hospital Research Institute (OHRI)

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

University Health Network

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide; Abiraterone Acetate; Prednisone; Docetaxel; niraparib; atezolizumab

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)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Martin E Gleave, MD

  University of British Columbia

  STUDY CHAIR

Central Study Contacts

Martin E Gleave, MD

CONTACT

604-875-5006; m.gleave@ubc.ca

Tiiu Sildva, PhD

CONTACT

tiiu.sildva@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator/Study Chair

Study Record Dates

• First Submitted: March 12, 2021
• First Posted: March 23, 2021
• Study Start: September 21, 2021
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: December 16, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); CA (4)