Phase 1
N=6
Treatment of Castration Resistant Prostate Cancer Using Multi-Targeted Recombinant Ad5 PSA/MUC1/Brachyury Based Immunotherapy Vaccines
Prostatic Neoplasms · Prostatic Cancer
Bottom Line
View on ClinicalTrials.gov: NCT03481816 ↗Enrolled (actual)
6
Serious AEs
11.1%
Results posted
Dec 2020
Primary outcome: Primary: Number of Participants With Dose-Limiting Toxicities — 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- ETBX-071; adenoviral PSA vaccine (Biological); ETBX-061; adenoviral MUC1 vaccine (Biological); ETBX-051; adenoviral brachyury vaccine (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Male
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Jan 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose-Limiting Toxicities |
0; 0 | — |
| PRIMARY Recommended Phase 2 Dose |
500000000000 | — |
| SECONDARY Percentage of Participants With an Objective Response |
0; 8.3; 0; 0 | — |
| SECONDARY Percentage of Participants With a Disease Control Rate (DCR) Lasting for at Least 6 Months |
0; 8.3; 0; 0; 0; 41.6 | — |
| SECONDARY Duration of Response |
16 | — |
| SECONDARY Progression-free Survival (PFS) |
22 | — |
| SECONDARY Overall Survival (OS) |
12.2; NA | — |
| SECONDARY Percentage of Overall Survival (OS) Probability at 12 Months and 24 Months |
50.0; 100; 33.3; 100 | — |
| SECONDARY Prostate-Specific Antigen Doubling Time (PSA DT) at Week 14 and End of Study |
NA; 2.4; NA; 4.3 | — |
| SECONDARY Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) |
6; 12 | — |
Summary
Background:
Metastatic castration resistant prostate cancer (mCRPC) keeps growing even when the amount of testosterone in the body is reduced to very low levels. mCRPC is incurable. Researchers want to develop vaccines to teach the immune system to target and kill cancer cells. They want to test three of these vaccines (ETBX-071, ETBX-061, and ETBX-051) against mCRPC.
Objective:
To test the safety of combination ETBX-071, ETBX-061, and ETBX-051 and to study their effects on the immune system.
Eligibility:
People ages 18 and older with mCRPC that has not responded to standard therapies
Design:
Participants will be screened with:
Medical history
Physical exam
Blood, urine, and heart tests
Computed tomography (CT) or magnetic resonance imaging (MRI) scans
Bone scan
Participants will get the vaccines as shots under the skin every 3 weeks for 3 doses. They may then have the shots every 8 weeks for up to 1 year.
Participants will keep a diary to record any symptoms from the vaccines.
Participants will have blood tests each time they get the vaccines. They will also have scans and other tests to measure the effect the vaccines have on their tumors.
Participants will have a visit within 28 days after their last treatment. This includes a physical exam and blood and urine tests.
Participants will then be contacted by phone every 3 months for the first year, every 6 months for the next 2 years, and every 12 months for another 2 years.
Participants will be asked to join a long-term follow up study.
Eligibility Criteria
- INCLUSION CRITERIA:
- Age more than or equal to 18 years (male).
- Ability to understand and provide signed informed consent that fulfills Institutional Review Board (IRB)s guidelines.
- Cytologically or histologically confirmed prostate cancer for which no curative standard approved therapy is available by either the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center or Walter Reed National Military Medical Center at Bethesda prior to starting this study. If no pathologic specimen is available, patients may enroll with a pathologists report showing a histological diagnosis of prostate cancer and a clinical course consistent with the disease.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Subjects who have received prior prostate specific antigen (PSA), mucin1 (MUC1), and/or brachyury-targeted immunotherapy (e.g. vaccine) are eligible for this trial if this treatment was discontinued at least 3 months prior to enrollment.
- Resolution of all toxic side effects of prior chemotherapy, radiotherapy, or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade less than or equal to1.
- Adequate hematologic function at screening, as follows:
- Absolute neutrophil count (ANC) greater than or equal to x 10 to the ninth power/L
- Hemoglobin more than or equa to 9 g/dL
- Platelets more than or equal to 75,000/microliter.
- Prothrombin (PT)-international normalized ratio (INR) 1 week (2 separate increasing values over a minimum of 2ng/ml (Prostrate Cancer Working Group 2 (PCWG2) PSA eligibility criteria). If patients had been on flutamide, PSA progression is documented 4 weeks or more after withdrawal. For patients on bicalutamide or nilutamide disease progression is documented 6 or more weeks after withdrawal. The requirement for a 4-6 week withdrawal period following discontinuation of flutamide, nilutamide or bicalutamide only applies to patients who have been on these drugs for at least the prior 6 months. For all other patients, they must stop bicalutamide, nilutamide or flutamide the day prior to enrollment.
- Patients must agree to continue to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone analogue/antagonist or bilateral orchiectomy
- Prior treatment with immunotherapy, hormonal therapy, radium 223, chemotherapy and/or other experimental therapy is allowed.
EXCLUSION CRITERIA
- Treatment with an investigational drug study within 28 days of before starting on study treatment.
- Subjects with concurrent cytotoxic chemotherapy or radiation therapy. There must be at least 28 days between any other prior chemotherapy (or radiotherapy) and study treatment. Prior antibody therapy must be discontinued 8 weeks prior to start of study treatment. Prior hormonal therapy can be discontinued 24 hours prior to start of study treatment.
- Any prior PSA, MUC1, and/or brachyury-targeted immunotherapy (e.g., vaccine) must have been discontinued at least 12 weeks before initiation of study treatment. Subjects must have recovered from all acute toxicities from prior treatment prior to screening for this study.
- Prior treatment with Adenovirus-Based vectors immunotherapy
- Known active brain or central nervous system metastasis, or seizures requiring anticonvulsant treatment, cerebrovascular accident, or transient ischemic attack (< 6 months prior to enrollment).
- Subjects with a history of autoimmune disease (active or past), such as but not restricted to inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Autoimmune-related thyroid disease, type I diabetes and vitiligo are permitted if the condition is well controlled.
- Subjects with serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, or other illness considered by the Investigator as high risk for investigational drug
Data sourced from ClinicalTrials.gov (NCT03481816). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.