Combination Immunotherapy in Biochemically Recurrent Prostate Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03315871|
Recruitment Status : Recruiting
First Posted : October 20, 2017
Last Update Posted : January 25, 2019
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.
To see if the combination treatment of PROSTVAC, CV301, and MSB0011359C (M7824) can induce an anti-tumor attack in people with biochemically recurrent prostate cancer.
People ages 18 and older with certain kinds of prostate cancer
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.
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Biological: PROSTVAC-V Biological: PROSTVAC-F Drug: MSB0011359C (M7824) Biological: CV301||Phase 2|
- Androgen deprivation therapy (ADT) and surveillance are treatment options for prostate cancer patients with biochemical progression after localized therapy (biochemically recurrent prostate cancer). The primary goal in these patients is to prevent morbidity from their cancer that results from disease progression and metastatic disease on conventional imaging.
- ADT can lower the PSA in these patients, but because of its substantial side effect profile and ambiguous long term impact, it is generally deferred by most patients until there is a rapid escalation in their PSA.
- Immunotherapy presents an alternative option for these patients that is especially attractive because it is not associated with substantial toxicity. Also, since immunotherapy can have lasting effects after treatment due to a sustained activated immune response, patients will not be required to take these treatments indefinitely to potentially benefit clinically.
- Current and previous clinical trials have demonstrated that single agent immunotherapy can impact PSA in patients in this population.
- The focus of this study is to determine if combination immunotherapy with immune-cell mobilizing vaccines can initiate an immune response in the first 4 months that is then augmented by an immune checkpoint inhibitor in the following 3 months.
- In addition to PSA responses (the primary metric in this population), safety, changes in immune responses, and PSA kinetics will also be evaluated.
- Safety Lead-In: To evaluate the safety and tolerability of combination immunotherapy in patients with castration-resistant prostate cancer
- Biochemical Recurrence: To determine if the combination immunotherapy can induce a 30% decline in PSA in 28% of patients with biochemically recurrent prostate cancer.
Key Eligibility Criteria (for biochemical recurrence):
- Histologically confirmed adenocarcinoma of the prostate
- Patients with negative CT Scan and Tc-99m Bone Scan
- Patients with a PSA over 0.8 ng/ml for patients following radical prostatectomy or for patients following definitive radiation therapy: a rise in PSA of greater than or equal to 2 ng/mL above the nadir
- Patients with a PSA doubling time of 5-15 months
- No history of active autoimmune disease or history of organ compromising autoimmune disease
- ECOG 0-1
- Safety lead-in cohort will evaluate 6 patients with castration resistant prostate cancer
- Single arm study
- Accrual goal is a total of 31 evaluable patients; 6 in an initial safety cohort and 25 to evaluate response
- Patients from an on-going study (NCT02649439) with nearly identical eligibility can serve as a contemporary control for secondary endpoints
- Following the safety lead-in, all patients will be enrolled and undergo a surveillance period during which 4 consecutive monthly PSA values will be captured by the NIH labs.
- After surveillance period, patients will be treated with 2 vaccines concurrently, Prostvac and CV301, during months 1-4. For months 5-7, MSB0011359C [an anti-PD-L1 antibody (avelumab) with TGFbeta-Trap molecule] will be added to the regimen.
- Patients will be monitored for on-treatment and post-treatment PSA, immune and imaging responses.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of Combination Immunotherapy in Biochemically Recurrent Prostate Cancer|
|Actual Study Start Date :||March 20, 2018|
|Estimated Primary Completion Date :||December 1, 2019|
|Estimated Study Completion Date :||December 1, 2020|
Recombinant vaccinia virus vector vaccine of the genus Orthopoxvirus. Administered by subcutaneous injection.
Recombinant fowlpox virus vector vaccine of the genus Avipoxvirus. Administered by subcutaneous injection.
Drug: MSB0011359C (M7824)
Fully human bi-functional fusion protein that combines lgG1 anti-PD-L1 and TGFbetaRII as a monoclonal antibody administered visa IV infusion over 1 hour.
Recombinant vaccinia virus vaccine of the genus Avipoxvirus. Administered subcutaneously.
- Fraction of evaluable subjects who experience at least a 30% decline from the maximum to the minimum PSA value while on study [ Time Frame: 6 months , one year ]
- Fraction of subjects with grade 3 and grade 4 adverse events [ Time Frame: 6 weeks ]
- Slope of the PSA change over time [ Time Frame: end of treatment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03315871
|Contact: Anna C Couvillon, C.R.N.P.||(240) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Ravi A Madan, M.D.||National Cancer Institute (NCI)|