Multi-Targeted Recombinant Ad5 (CEA/MUC1/Brachyury) Based Immunotherapy Vaccine Regimen in People With Advanced Cancer
- Conditions
- Prostate CancerBreast CancerLung CancerNeoplasmsColon Cancer
- Interventions
- Biological: ETBX-051; adenoviral brachyury vaccineBiological: ETBX-061; adenoviral Mucin-1 (MUC1) vaccineBiological: ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine
- Registration Number
- NCT03384316
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief 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.
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- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 11
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 2/Arm 2 - Dose Expansion ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine Dose Expansion 1/Arm 1-Dose De-Escalation ETBX-061; adenoviral Mucin-1 (MUC1) vaccine Dose De-Escalation 1/Arm 1-Dose De-Escalation ETBX-051; adenoviral brachyury vaccine Dose De-Escalation 1/Arm 1-Dose De-Escalation ETBX-011; adenoviral Carcinoembryonic antigen (CEA) vaccine Dose De-Escalation 2/Arm 2 - Dose Expansion ETBX-051; adenoviral brachyury vaccine Dose Expansion 2/Arm 2 - Dose Expansion ETBX-061; adenoviral Mucin-1 (MUC1) vaccine Dose Expansion
- Primary Outcome Measures
Name Time Method Recommended Phase 2 Dose (RP2D) RP2D was based upon evaluation of DLTs. Participants were followed for DLTs from the first dose of vaccine for 3 weeks. RP2D is defined as ≤ 1 of 6 of the initial 6 subjects who experience a dose limiting toxicity (DLT), than this dose level will be defined as the RP2D. A DLT is defined as any Grade 3 or greater toxicity that is possibly related to the vaccine and as defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 with the exception of transient (≤ 24 hours) Grade 3 flu-like symptoms or fever, which is controlled with medical management (≤ 24 hours) Grade 3 fatigue, skin reactions or rash, headache, nausea, emesis that resolves to Grade ≤ 1 or asymptomatic grade 3 amylase/lipase elevation.
Number of Participants With Serious and Non-serious Adverse Events Date treatment consent signed to date off study, approximately 16 months and 6 days. Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
- Secondary Outcome Measures
Name Time Method Number of Participants Who Achieve an Objective Confirmed Complete or Partial Response Assessed by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Approximately 3.5 months Objective response is determined by participants whose tumors shrunk after therapy assessed by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \<10 mm. Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Number of Patients With Disease Control (Confirmed Response or Stable Disease (SD)) Lasting for at Least 6 Months up to 6 months Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for Partial Response (PR) nor sufficient increase to qualify for Progressive Disease (taking as reference the smallest sum diameters while on study).
Progression-free Survival (PFS) up to 12 months The amount of time a subject survives without disease progression after treatment. Progression is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) and is at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum diameters while on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of 5 mm. (Note: the appearance of one or more lesions is also considered progression).
Overall Survival (OS) up to 12 months OS is defined as the amount of time a subject survives after therapy assessed from the date of first treatment to the date of death (any cause).
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States