Multi-Targeted Recombinant Ad5 (CEA/MUC1/Brachyury) Based Immunotherapy Vaccine Regimen in People With Advanced Cancer
Condition: Neoplasms; Prostate Cancer; Lung Cancer; Breast Cancer; Colon Cancer
MeSH terms: Colonic Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      ETBX-011, ETBX-061, and ETBX-051 are cancer vaccines. Their goal is to teach the immune
      system to target and kill cancer cells. The vaccines target 3 proteins found in many types of
      cancer. Researchers think targeting all 3 proteins in unison will have the best results.

      Objective:

      To test the safety of combining ETBX-011, ETBX-061, and ETBX-051 and their effects on the
      immune system.

      Eligibility:

      People ages 18 and older with advanced cancer that has not responded to standard therapies

      Design:

      Participants will be screened with:

      Medical history

      Physical exam

      Blood, urine, and heart tests

      Scan: They will lie in a machine that takes pictures of the body.

      Participants will receive the 3 vaccines through 3 shots under the skin every 3 weeks for 3
      doses, then every 8 weeks for up to 1 year. They will have blood and urine tests at each
      vaccine visit. They will have scans and other measurements of their tumor after 9 weeks and
      then at their vaccine visits every 8 weeks.

      Participants will keep a diary of symptoms at the injection site.

      Participants will have a visit 90 days after their final treatment. This will include a
      physical exam and blood and urine tests. If they have any ongoing side effects, they will be
      followed until these end or are not changing.

      After this visit, they will be called every 3 months for the first year, every 6 months for
      the next 2 years, then every 12 months for another 2 years to see how they are doing.

      Participants will have the option to enroll in a long-term follow-up study.

      ...
    

Detailed description: 
      Background:

        -  The overall goal of the current project is to expand our immunotherapeutic approach for
           the treatment of advanced 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 vaccine targeting three (3) human tumor associated antigens
           (TAA), carcinoembryonic antigen (CEA), mucin-1 (MUC1), and brachyury, respectively has
           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-011/ETBX-061/ETBX-051), when administered subcutaneously
      (SC) to subjects with advanced solid tumors

      Eligibility:

        -  Subjects age 18 and older with cytologically or histologically confirmed locally
           advanced or metastatic solid tumor malignancy who have completed or had disease
           progression on at least one prior line of disease-appropriate therapy or who are not
           candidates for therapy of proven efficacy for their disease.

        -  Subjects may have measurable or non-measurable but evaluable disease. Subjects with
           surgically resected metastatic disease at high risk of relapse are also eligible.

        -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1

        -  Adequate organ and bone marrow function

        -  Subjects with active autoimmune diseases requiring systemic treatment and subjects
           requiring systemic steroids (except for physiologic doses for steroid replacement) are
           not allowed

      Design:

        -  This is a Phase I trial in subjects with advanced cancer. A combination of three
           therapeutic vaccines (ETBX-011, ETBX-51, EBX-61) using the same modified Adenovirus
           vector backbone, separately encoding three well-studied tumor-associated antigens will
           be assessed. The vaccine will be tested at a single dose level, and a dose de-escalation
           design (if required). The dose level of each vaccine tested will be 5x1011 VP. This dose
           has been found in prior phase 1 testing of Ad5 [E1-, E2b-]-CEA(6D) (ETBX-011) to be well
           tolerated (with no dose-limiting toxicities (DLTs) or related Serious adverse events
           (SAEs), and optimal for induction of immune responses. Each of the three vaccines will
           be administered subcutaneously (SC) at separate injection sites (proximal limb,
           preferably the thigh), every 3 weeks for 3 doses, then bi-monthly (every 8 week) boosts
           for up to a year.

        -  Up to six patients will be enrolled at Dose Level 1. If less than or equal to l of 6
           patients experience a DLT, initiation of the dose expansion phase will occur. If greater
           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 Dose Level -1
           (1x10^11 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 greater than or equal to 2 of 6 experience DLT at Dose
           Level -1, then a protocol amendment may be written to evaluate a further dose
           de-escalation.

        -  A dose expansion phase of study will be enrolled after the MTD of the combination
           vaccine has been determined. An additional 4 subjects will be enrolled in the dose
           expansion component of the trial, for a total of 10 subjects at the MTD.

        -  The ETBX-011, ETBX-51 and ETBX-61 vaccines will be administered SC every 3 weeks for 3
           doses, and then bi monthly boosts for up to a year. Evaluations including immunological
           assessments will be carried out at baseline, on days of vaccination, and after the last
           vaccination.
    

Intervention name(s): ETBX-051; adenoviral brachyury vaccine; ETBX-061; adenoviral Mucin-1 (MUC1) vaccine; ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine
Intervention type(s): Biological; Biological; Biological
Intervention description(s): immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year; immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year; immunotherapeutic vaccine administered subcutaneously every 3 weeks for 3 doses, and then every 8 weeks for up to a year
Intervention MeSH terms: Vaccines
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Combination Vaccine; Adenoviral; ETBX-011; ETBX-061; ETBX-051