Combination Immunotherapy in Biochemically Recurrent Prostate Cancer
- Conditions
- Prostate Cancer
- Interventions
- Registration Number
- NCT03315871
- Lead Sponsor
- National Cancer Institute (NCI)
- 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, CV301, and MSB0011359C (M7824) can induce an anti-tumor attack 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.
- Detailed Description
Background:
Androgen deprivation therapy (ADT) and surveillance are treatment options for prostate cancer patients with biochemical progression after localized therapy (i.e., biochemically recurrent \[BCR\] 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.
Objectives:
Primary Objectives:
Safety Lead-In: To evaluate the safety and tolerability of combination immunotherapy in participants with castration-resistant prostate cancer
Biochemical Recurrence: To determine if the combination immunotherapy can induce a 30% decline in PSA in 28% of participants with biochemically recurrent prostate cancer.
Eligibility Criteria (for biochemical recurrence):
Histologically confirmed adenocarcinoma of the prostate
Participants with negative CT Scan and Tc-99m Bone Scan
Participants with a PSA over 0.8 ng/ml for participants following radical prostatectomy or for participants following definitive radiation therapy: a rise in PSA of \>= 2 ng/mL above the nadir
Participants 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 participants with castration resistant prostate cancer
Design:
Three-arm, non-randomized study
Accrual goal is a total of 37 evaluable participants (6 in an initial safety cohort, 6 participants who received M7824 as part of the initial investigation and 25 homogenously treated participants) to evaluate response
Participants 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 participants will be enrolled and may undergo a surveillance period during which up to 4 consecutive monthly PSA values will be captured by the labs.
After surveillance period, if applicable, participants will be treated with 2 vaccines concurrently, Prostvac and CV301, during months 1-4. For months 5-7, MSB0011359C \[an anti-PD-L1 antibody (avelumab) with TGF(Beta)-Trap molecule\] will be added to the regimen.
-Effective with amendment v7/29/2021, MSB0011359C will no longer be given as part of the treatment combination for the Biochemical Recurrence cohort (Arms 2 and 3)
Participants will be monitored for on-treatment and post-treatment PSA, immune and imaging responses.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1/combination therapy (closed December 2018) PROSTVAC-F Prostvac + CV301+ MSB0011359C 1/combination therapy (closed December 2018) MSB0011359C (M7824) Prostvac + CV301+ MSB0011359C 1/combination therapy (closed December 2018) CV301 Prostvac + CV301+ MSB0011359C 2/combination therapy + surveillance (closed) PROSTVAC-V Surveillance followed by Prostvac + CV301 then Prostvac + CV301 + MSB0011359C 2/combination therapy + surveillance (closed) PROSTVAC-F Surveillance followed by Prostvac + CV301 then Prostvac + CV301 + MSB0011359C 2/combination therapy + surveillance (closed) MSB0011359C (M7824) Surveillance followed by Prostvac + CV301 then Prostvac + CV301 + MSB0011359C 2/combination therapy + surveillance (closed) CV301 Surveillance followed by Prostvac + CV301 then Prostvac + CV301 + MSB0011359C 3/combination vaccine therapy +/- surveillance PROSTVAC-V Surveillance as needed followed by Prostvac + CV301 1/combination therapy (closed December 2018) PROSTVAC-V Prostvac + CV301+ MSB0011359C 3/combination vaccine therapy +/- surveillance CV301 Surveillance as needed followed by Prostvac + CV301 3/combination vaccine therapy +/- surveillance PROSTVAC-F Surveillance as needed followed by Prostvac + CV301
- Primary Outcome Measures
Name Time Method deterimine if combination immunotherapy can result in 30% decline in PSA 6 months, one year fraction of evaluable subjects who experience at least a 30% decline from the maximum to the minimum PSA value while on study
- Secondary Outcome Measures
Name Time Method slope of the PSA change over time end of treatment The slopes obtained after administering the vaccines alone or in combination with the checkpoint inhibitor will be tested vs the slopes obtained prior to administering the vaccines, using a two-tailed 0.05 significance level paired t-test or Wilcoxon signed rank test (if the paired differences are not normally distributed)
fraction of subjects with grade 3 and grade 4 adverse events 6 weeks Reprting the grade of adverse events noted in each participant and reporting the fraction with grade 3 and grade 4 adverse events
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
šŗšøBethesda, Maryland, United States