Treatment of Castration Resistant Prostate Cancer Using Multi-Targeted Recombinant Ad5 PSA/MUC1/Brachyury Based Immunotherapy Vaccines

Prostatic Neoplasms Clinical Trial

Official title: Treatment of Patients With Castration Resistant Prostate Cancer Using a Multi-Targeted Recombinant Ad5 PSA/MUC1/Brachyury Based Immunotherapy Vaccines

Status Completed

Clinical Trial 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.

Clinical Trial Description

Background:

• The overall goal of the current project is to expand our immunotherapeutic approach for the treatment of prostate cancer employing a multi-targeted approach.

• Therapeutic cancer vaccines targeting overexpressed proteins offer a potential method to activate T cells against tumors.

• A novel adenovirus based vaccines targeting three (3) human tumor associated antigens (TAA), Prostate specific antigen (PSA), Mucin 1 (MUC1), and brachyury, respectively have demonstrated anti-tumor cytolytic T cell responses in pre-clinical animal models of cancer.

Objectives:

-To determine the overall safety and recommended phase 2 dose of a combination of three immunotherapeutic vaccines (ETBX-071, ETBX-061, and ETBX-051) when administered subcutaneously (SC) to subjects with metastatic castration resistant prostate cancer

Eligibility:

• Subjects age 18 and older with cytologically or histologically confirmed prostate cancer for which no curative standard approved therapy is available.

• Metastatic Castration Resistant Prostate Cancer (mCRPC) patients with rising PSA or progressive disease despite castration levels of testosterone.

• Prior treatment with immunotherapy hormonal therapy, radiotherapy, chemotherapy, and/or other experimental therapy is allowed.

• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1

• Adequate organ and bone marrow function

• Subjects with a history of autoimmune disease (active or past) and subjects requiring systemic steroids are not eligible (physiologic doses of steroids for steroid replacement as well as nasal, topical and inhaled steroids are allowed). Autoimmune-related thyroid disease, type I diabetes and vitiligo are permitted if the condition is well controlled.

Design:

• This is a Phase I trial in subjects with mCRPC. A combination of three therapeutic vaccines (ETBX-071, ETBX-061, and ETBX-051) which use the same modified Adenovirus vector backbone, separately encoding three well studied TAA,PSA, MUC1, and brachyury, respectively) will be assessed. The vaccines will be tested at standard dose levels, with a dose de-escalation (if required) design employed. The dose level of each vaccine tested will be 5x10 to the eleventh power VP. This dose has been found in a prior phase 1 testing of a similar vaccine Ad5 [E1-, E2b-]-carcinoembryonic antigen (CEA)(6D) (ETBX-011) to be well tolerated (with no dose-limiting toxicities (DLTs) or related serious adverse events(SAEs), and be optimal for induction of immune responses.

• Up to six patients will be enrolled at dose level 1. If less than or equal to 1 of 6 patients experience a DLT, an initiation of the dose expansion phase will occur. If more than or equal to 2 of 6 experience DLT at dose level 1, then dose de-escalation will occur. Up to six patients will be enrolled at the lower dose level (-1) (1x10 to the eleventh power VP). If less than or equal to 1 of 6 patients experience a DLT, then the maximum tolerated (MTD) will be declared at this dose, and initiation of the dose expansion phase will occur. If more than or equal to 2 of 6 experience DLT at dose level -1, then a further dose de-escalation will occur. Up to six patients will be enrolled at the lower dose level (-2) (5x10 to the tenth power VP). If less than or equal to 1 of 6 patients experience a DLT, then the maximum tolerated (MTD) will be declared at this dose, and initiation of the dose expansion phase will occur. If more than or equal to 2 of 6 experience DLT at dose level -2, then the study will be stopped.

• A dose expansion phase of study will be enrolled after the MTD of the vaccines have been determined. An additional 12 subjects will be enrolled in the dose expansion component of the trial, for a total of 18 subjects at the MTD.

• The ETBX-051, ETBX-61 and ETBX-71 vaccines will be administered subcutaneously (SC) at separate injection sites (proximal limb, preferably the thigh), will be administered SC every 3 weeks for 3 doses (dose de-escalation cohorts) followed by boosts every 8 weeks for 1 year (only patients enrolled in dose expansion cohort). ;

Related Conditions & MeSH terms

• Prostatic Cancer
• Prostatic Neoplasms

• NCT number: NCT03481816
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: July 24, 2018
• Completion date: March 9, 2021