Combination Immunotherapy in Biochemically Recurrent Prostate Cancer
Phase II Trial of Combination Immunotherapy in Biochemically Recurrent Prostate Cancer
2 other identifiers
interventional
40
1 country
1
Brief Summary
Background: Some people with prostate cancer have a rise in prostate-specific antigen (PSA). This can happen even after treatments like radiation and surgery. Androgen deprivation therapy (ADT) drugs and close monitoring are one standard way to treat this group of people. Another way is to monitor people and their PSA values over time. Researchers want to see if a combination of new drugs can help these people. Objective: To see if the combination treatment of PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec vaccinia), CV301, and MSB0011359C (M7824) can induce an anti-tumor impact in people with biochemically recurrent prostate cancer. Eligibility: People ages 18 and older with certain kinds of prostate cancer Design: Participants will be screened with
- Medical history
- Physical exam
- Blood and urine tests
- A scan of the neck, chest, abdomen, and pelvis
- A bone scan A sample of tissue that was already taken will be tested. This will confirm the diagnosis, stage, and disease status. Some participants will have close monitoring with four monthly PSA checks. All participants will get two study drugs as shots under the skin. They will get the third drug in a vein. They will get the drugs over at least 7 months. Their vital signs will be checked before they get the drugs and for up to 1 hour after. Participants will have frequent study visits. They will have physical exams, urine and blood tests, and scans. Participants will return to the clinic about 4 weeks after they stop taking the study drugs. They will have a medical history, physical exam, and blood tests. They may also have long-term follow-up visits.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2 prostate-cancer
Started Mar 2018
Typical duration for phase_2 prostate-cancer
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 18, 2017
CompletedFirst Posted
Study publicly available on registry
October 20, 2017
CompletedStudy Start
First participant enrolled
March 20, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 4, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
June 4, 2024
CompletedResults Posted
Study results publicly available
June 19, 2025
CompletedJune 19, 2025
June 1, 2025
6.2 years
October 18, 2017
May 2, 2025
June 4, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of Participants With a Toxicity
Percentage of participants with a toxicity assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
At the end of therapy (7 months)
Prostate Specific Antigen (PSA) Response
Proportion of evaluable participants who experience at least a 30% decline. PSA is a tumor marker in prostate cancer and elevated in participants with this stage of disease. Declines of 30% can be associated with favorable clinical outcomes.
End of treatment (7 months)
Secondary Outcomes (2)
Number of Participants With Related and/or Unrelated Grade 3 and Grade 4 Adverse Events.
6 weeks
Number of Evaluable Participants With Biochemical Recurrence (BCR) With a 20% Change in PSA Doubling Time
End of treatment after 7 months
Other Outcomes (1)
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Adverse Events was monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, an average of 32 weeks.
Study Arms (3)
1/Safety Lead-in Combination Therapy (closed December 2018)
EXPERIMENTALProstvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301+ MSB0011359C (M7824)
2/Biochemical Recurrence: Combination Therapy + Surveillance (closed)
EXPERIMENTALSurveillance followed by Prostvac ( rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301 then Prostvac + CV301 + MSB0011359C (M7824)
3/Biochemical Recurrence: Combination Antigen Direct Immunotherapy +/- Surveillance
EXPERIMENTALSurveillance as needed followed by Prostvac (rilimogene galvacirepvec/rilimogene glafolivec vaccinia) + CV301
Interventions
Recombinant vaccinia virus vector antigen direct immunotherapy of the genus Orthopoxvirus. Administered by subcutaneous injection.
Recombinant fowlpox virus vector Antigen direct immunotherapy of the genus Avipoxvirus. Administered by subcutaneous injection.
Fully human bifunctional fusion protein that combines immunoglobulin G1 (IgG1) anti-programmed death-ligand 1 (PD-L1) and Transforming growth factor, beta receptor II (TGFbetaRII) as a monoclonal antibody. Administered via intravenous (IV) infusion over 1 hour.
Recombinant vaccinia virus Antigen direct immunotherapy of the genus Avipoxvirus. Administered subcutaneously.
Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.
Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.
Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.
Biochemical recurrence group only. Screening, prior to Antigen direct immunotherapy therapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.
Screening, prior to Antigen direct immunotherapy, end of study therapy, then every 6 months as long as participants remain in follow-up. And as clinically indicated after one year.
Eligibility Criteria
You may qualify if:
- Histopathological documentation of prostate cancer confirmed in either the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center, or Walter Reed National Military Medical Center prior to enrollment. If no pathologic specimen is available, participants may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
- Recovery to baseline from acute toxicity related to prior therapy, including surgery and radiation. (28 days removed from last systemic therapy, 14 days removed from last radiation therapy).
- Hepatic function eligibility parameters (within 16 days before starting therapy):
- Bilirubin less than or equal to upper limit of normal (ULN) (OR in participants with Gilbert's syndrome, a total bilirubin less than or equal to 3.0), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 1.5 times upper limit of normal.
- Adequate renal function defined by an estimated creatinine clearance \> 50 mL/min according to the Cockcroft-Gault formula or by measure of creatinine clearance from 24-hour urine collection.
- No other active malignancies within the past 36 months (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder) or life-threatening illnesses.
- Willing to travel to the NIH for follow-up visits.
- years of age or older.
- Able to understand and sign informed consent.
- The effects Prostvac (rilimogene galvacirepvec/rilimogene glafolivec) and CV301 on the developing human fetus are unknown. For this reason, men must agree to use highly effective contraception (that is, methods with a failure rate of less than 1% per year) prior to study entry, for the duration of study therapy and at least four months after the last treatment administration. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.
- Castrate testosterone level (\<50ng/dl or 1.7nmol /L)
- Progressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone:
- Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer
- For Biochemical Recurrence:
- Prostate-specific antigen (PSA) progression defined by sequence of rising values separated by \>1 week (2 separate increasing values over a minimum of 2ng/ml (Prostate Cancer Working Group 2 (PCWG2) PSA eligibility criteria). If participants had been on flutamide, PSA progression is documented 4 weeks or more after withdrawal. For participants on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal.
- +21 more criteria
You may not qualify if:
- Immunocompromised status due to:
- Human immunodeficiency virus (HIV) positivity.
- Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease.
- Participants with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed.
- Participants with diabetes type I, vitiligo, or alopecia are allowed.
- Other immunodeficiency diseases
- Splenectomy
- Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (e.g., corneal transplant, hair transplant).
- Chronic administration (defined as daily or every other day for continued use \> 14 days) of systemic corticosteroids within 28 days before the first planned dose of investigational therapy. Use of corticosteroids with minimal systemic absorption (e.g., inhaled steroids, nasal sprays, and topical agents) is allowed.
- Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with participants ability to carry out the treatment program.
- Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto).
- History of prior chemotherapy (chemotherapy allowed for lead-in cohort in castration resistant disease.)
- History of prior immunotherapy within the last 3 years (immunotherapy allowed for lead-in cohort in castration resistant disease.)
- Receipt of an investigational agent within 28 days (or 56 days for an antibody-based therapy) before the first planned dose of study drugs.
- Major surgery within 4 weeks prior to enrollment
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Ravi A. Madan
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Ravi A Madan, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
October 18, 2017
First Posted
October 20, 2017
Study Start
March 20, 2018
Primary Completion
June 4, 2024
Study Completion
June 4, 2024
Last Updated
June 19, 2025
Results First Posted
June 19, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
- Access Criteria
- Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).