- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03637543
Nivolumab in Patients With High-Risk Biochemically Recurrent Prostate Cancer
A Phase 2 Study of Nivolumab in Patients With High-Risk Biochemically Recurrent Prostate Cancer
This research study is studying an immune-based cancer drug as a possible treatment for prostate cancer.
The drug involved in this study is:
-Nivolumab
Study Overview
Detailed Description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved nivolumab for this specific disease but it has been approved for other uses. Nivolumab is an antibody inhibitor of the programmed death-1 (PD-1) pathway. By blocking PD-1, this medication may allow the immune system to recognize and fight cancer.
In this research study, the investigators are investigating whether nivolumab has any activity in patients who have a rising PSA (prostate specific antigen) after previously undergoing surgery or radiation for prostate cancer. Although nivolumab was previously not found to have significant effect in advanced prostate cancer after all other therapies had failed, based on new research, the investigators are testing whether nivolumab could have a greater effect earlier in the disease course and before patients receive hormone therapies.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: David J. Einstein, MD
- Phone Number: 617-667-2100
- Email: deinstei@bidmc.harvard.edu
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center
-
Boston, Massachusetts, United States, 02215
- Dana Farber Cancer Institute
-
Boston, Massachusetts, United States, 02135
- St. Elizabeth's Medical Center
-
South Weymouth, Massachusetts, United States, 02190
- DFCI South Shore
-
-
New Hampshire
-
Londonderry, New Hampshire, United States, 03053
- DFCI Londonderry
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients must have signed an informed-consent form indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study.
- Patients must have a history of prostate adenocarcinoma (adenocarcinoma must be the primary histology; secondary components of variant histologies are acceptable) confirmed on biopsy and treated with primary radical prostatectomy (RP) or definitive radiation (RT). Prior salvage RT is acceptable.
Patients must have experienced biochemical recurrence (BCR) plus have minimum PSA values noted below:
- Following primary RP: Any detectable rising PSA after RP (or after salvage RT if performed), minimum PSA 1.0 at time of screening
- Following primary RT: PSA rise to ≥2 ng/mL above the nadir
- No evidence of metastases on conventional imaging (CT or MRI plus bone scan)
- PSA doubling time (PSADT) <10 months --PSADT: calculated as per Prostate Cancer Working Group 3 (PCWG3) and the Memorial Sloan Kettering Cancer Center calculator: (https://www.mskcc.org/nomograms/prostate/psa_doubling_time)
With linear regression model of normal logarithm of PSA and time, based on:
- At least 3 consecutive PSA values with each value ≥0.2 ng/mL
Interval between first and last PSA values is ≥8 weeks but ≤12 months.
-Archival tissue is mandatory, either prostatectomy specimen or (in patients who received primary RT) diagnostic core biopsies. Patients must consent to next-generation sequencing performed on this tissue.
If diagnostic core biopsies are only available tissue, at least 3 cores must be involved by tumor
- Easteron Cooperative Oncology Group (ECOG) performance status 0-1
- Age ≥18 years
- Adequate organ and marrow function:
- System Laboratory Value
- Hematological
- White blood cell (WBC) ≥ 2000/µL
- Absolute Neutrophil Count (ANC) ≥ 1500/μL
- Platelets (Plt) ≥ 100 x103/μL
Hemoglobin (Hgb) > 9.0 g/dL (with or without transfusion)
-Renal
- Serum Creatinine ≤ 2 x ULN
- Hepatic
- Bilirubin1 ≤ 1.5× upper limit of normal (ULN)
- Aspartate aminotransferase (AST) ≤ 3 × ULN
Alanine aminotransferase (ALT) ≤ 3 × ULN
- Except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL
- Baseline testosterone ≥100 ng/dL
- Recovery from acute toxicity related to prior therapy, including surgery and radiation, or no treatment-related toxicity ≥ grade 2.
- History of prior malignancy or concurrent separate malignancy is not an exclusion criterion so long as the non-prostate malignancy is stable and does not require any treatment.
- Able to understand and sign informed consent and adhere to study procedures.
- Male patients whose female partners are of reproductive potential must agree to use a contraception during the trial period
Exclusion Criteria:
- Current use of ADT or plan to initiate ADT during trial period
- Major surgery or radiation therapy within 14 days of starting study treatment
- Subjects with active autoimmune disease. Patients with a history of autoimmune disease that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system, heart, lungs, kidneys, skin, and gastrointestinal tract will be allowed.
- Known history of immune deficiencies or chronic viral infections including HIV, hepatitis B (HBV), and hepatitis C (HCV) (patients with prior therapy for HBV or HCV is permitted if viral clearance was documented).
- Concurrent medical condition requiring use of systemic corticosteroids with prednisone >10 mg per day or equivalent. Use of inhaled, nasal, and topical steroids (applied to small body areas) is allowed.
- Current use (within past 4 weeks) of other prohibited medications including anti-cancer therapies, hormonal therapies, 5-alpha reductase inhibitors, and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto).
- Prior treatment with immune checkpoint inhibitors. (Prior cancer vaccines are allowed.)
- Serious intercurrent medical or psychiatric illness that, in the judgment of the investigator, would interfere with patient's ability to carry out the treatment program
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: PD-L1 Positive
-Nivolumab will be given on day 1 of a 28-day cycle intravenously
|
Nivolumab is an antibody inhibitor of the programmed death-1 (PD-1) pathway.
By blocking PD-1, this medication may allow the immune system to recognize and fight cancer
Other Names:
|
Experimental: PD-L1 Negative
-Nivolumab will be given on day 1 of a 28-day cycle intravenously
|
Nivolumab is an antibody inhibitor of the programmed death-1 (PD-1) pathway.
By blocking PD-1, this medication may allow the immune system to recognize and fight cancer
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease Control
Time Frame: 12 weeks
|
Proportion of patients with high-risk biochemically-recurrent (BCR) prostate cancer (PCa) that experiences decline or stabilization in PSA (without symptomatic/radiographic progression) after 12 weeks of nivolumab treatment
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Maximal change in prostate specific antigen (PSA) during nivolumab treatment
Time Frame: 2 years
|
2 years
|
Best PSA response during nivolumab treatment as an absolute change relative to baseline
Time Frame: 2 years
|
2 years
|
Change in PSA doubling time (PSADT) at end-of-study relative to baseline
Time Frame: 2 years
|
2 years
|
Time from enrollment to development of radiographic metastatic disease
Time Frame: 2 years
|
2 years
|
Time from enrollment to initiation of androgen deprivation therapy (ADT)
Time Frame: 2 years
|
2 years
|
Treatment-related adverse events as assessed by CTCAE v5.0
Time Frame: 2 years
|
2 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: David J. Einstein, MD, Beth Israel Deaconess Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Urogenital Diseases
- Male Urogenital Diseases
- Genital Diseases, Male
- Genital Diseases
- Prostatic Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
Other Study ID Numbers
- 18-249
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Prostate Cancer
-
Roswell Park Cancer InstituteRecruitingObesity | Overweight | Cancer Survivor | Prostate Adenocarcinoma | Stage I Prostate Cancer | Stage II Prostate Cancer | Stage III Prostate Cancer | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate Cancer | Stage IVA Prostate Cancer | Stage IVB Prostate Cancer | Stage A Prostate Cancer | Stage... and other conditionsUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Regeneron Pharmaceuticals; Prostate Cancer FoundationWithdrawnStage III Prostate Cancer | Stage IV Prostate Cancer | Stage IVA Prostate Cancer | Stage IVB Prostate Cancer | Stage IIIA Prostate Cancer | Stage IIIB Prostate Cancer | Stage IIIC Prostate Cancer
-
Jonsson Comprehensive Cancer CenterProgenics Pharmaceuticals, Inc.TerminatedRandomized Trial of PSMA PET Scan Before Definitive Radiation Therapy for Prostate Cancer (PSMA-dRT)Stage II Prostate Cancer AJCC v8 | Stage IIIA Prostate Cancer AJCC v8 | Stage IIIB Prostate Cancer AJCC v8 | Stage IIC Prostate Cancer AJCC v8 | Stage III Prostate Cancer AJCC v8 | Stage IIIC Prostate Cancer AJCC v8 | Stage IIA Prostate Cancer AJCC v8 | Stage IIB Prostate Cancer AJCC v8 | Stage I Prostate...United States
-
University of Southern CaliforniaNational Cancer Institute (NCI); SanofiTerminatedDiarrhea | Recurrent Prostate Cancer | Hormone-resistant Prostate Cancer | Stage I Prostate Cancer | Stage III Prostate Cancer | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI)CompletedRecurrent Prostate Cancer | Stage I Prostate Cancer | Stage III Prostate Cancer | Adenocarcinoma of the Prostate | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
Ohio State University Comprehensive Cancer CenterRiverside Methodist HospitalCompletedStage I Prostate Cancer | Stage III Prostate Cancer | Stage IV Prostate Cancer | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
Ryan Kohlbrenner, MDRadiological Society of North AmericaCompletedProstate Adenocarcinoma | Stage IV Prostate Cancer AJCC v8 | Prostate Carcinoma | Stage IIIA Prostate Cancer AJCC v8 | Stage IIIB Prostate Cancer AJCC v8 | Stage IIC Prostate Cancer AJCC v8 | Stage III Prostate Cancer AJCC v8 | Stage IIIC Prostate Cancer AJCC v8 | Stage IVA Prostate Cancer AJCC v8 | Stage...United States
-
Mayo ClinicNational Cancer Institute (NCI)WithdrawnStage I Prostate Cancer AJCC v8 | Stage II Prostate Cancer AJCC v8 | Stage IIIA Prostate Cancer AJCC v8 | Stage IIIB Prostate Cancer AJCC v8 | Stage IIC Prostate Cancer AJCC v8 | Stage III Prostate Cancer AJCC v8 | Stage IIIC Prostate Cancer AJCC v8 | Stage IIA Prostate Cancer AJCC v8 | Stage IIB Prostate...United States
-
University of California, IrvineCompletedRecurrent Prostate Cancer | Stage I Prostate Cancer | Stage III Prostate Cancer | Adenocarcinoma of the Prostate | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
-
Barbara Ann Karmanos Cancer InstituteGenentech, Inc.CompletedRecurrent Prostate Cancer | Stage I Prostate Cancer | Stage III Prostate Cancer | Adenocarcinoma of the Prostate | Stage IIA Prostate Cancer | Stage IIB Prostate CancerUnited States
Clinical Trials on Nivolumab
-
Universitair Ziekenhuis BrusselNot yet recruiting
-
Brown UniversityBristol-Myers Squibb; The Miriam Hospital; Rhode Island Hospital; Women and Infants...Terminated
-
Bristol-Myers SquibbRecruitingMelanomaSpain, United States, Italy, Chile, Greece, Argentina
-
Baptist Health South FloridaBristol-Myers Squibb; NovoCure Ltd.TerminatedRecurrent GlioblastomaUnited States
-
HUYABIO International, LLC.Bristol-Myers SquibbRecruitingUnresectable or Metastatic Melanoma | Progressive Brain MetastasisSpain, United States, Italy, Japan, Belgium, France, New Zealand, Brazil, Korea, Republic of, Australia, Germany, Singapore, Czechia, Austria, South Africa, United Kingdom, Puerto Rico
-
Michael B. Atkins, MDBristol-Myers Squibb; Hoosier Cancer Research NetworkActive, not recruitingAdvanced Renal Cell CarcinomaUnited States
-
Jason J. Luke, MDArray BioPharmaActive, not recruitingMelanoma | Renal Cell Carcinoma | Solid Tumor | Non-small Cell Lung Cancer | Head and Neck Squamous Cell CarcinomaUnited States
-
Bristol-Myers SquibbCompletedLung CancerItaly, United States, France, Russian Federation, Spain, Argentina, Belgium, Brazil, Canada, Chile, Czechia, Germany, Greece, Hungary, Mexico, Netherlands, Poland, Romania, Switzerland, Turkey, United Kingdom
-
National Health Research Institutes, TaiwanNational Taiwan University Hospital; Mackay Memorial Hospital; China Medical... and other collaboratorsRecruitingHepatocellular Carcinoma (HCC)Taiwan
-
IRCCS San RaffaeleBristol-Myers SquibbRecruiting