A Phase I/II Study of Active Immunotherapy With Ad5 [E1-,E2b-]-CEA(6D) Vaccine in Patients With Advanced or Metastatic Malignancies Expressing CEA
Overview
- Phase
- Phase 1
- Intervention
- Ad5 CEA Vaccine
- Conditions
- Not specified
- Sponsor
- NantCell, Inc.
- Enrollment
- 43
- Locations
- 2
- Primary Endpoint
- Number of Participants With Dose Limiting Toxicities
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief Summary
The purpose of this study is to find out what effects (good and bad) that a cancer vaccine has on you and your cancer. The cancer vaccine is called Ad5 [E1-, E2b-]-CEA(6D)or ETBX-011 and is made by Etubics. This vaccine is based on a virus called an adenovirus but it has been changed to express the protein CEA that is found on some cancer cells. Therefore, the vaccine can tell the immune system to attack cancer cells which make CEA. The investigators are trying to determine whether giving this virus is safe and whether this causes a strong immune system attack on the cancer. ETBX-011 is an investigational drug.
Detailed Description
This is a phase I/II study with the primary purpose to determine the safety of immunization with Ad5 \[E1-, E2B-\]-CEA(6D), in patients with advanced or metastatic CEA-expressing malignancies. The secondary objectives are to evaluate CEA-specific immune responses to the immunizations and to obtain preliminary data on clinical response rate. The study population consists of patients with a histologically confirmed diagnosis of metastatic malignancy that is CEA positive who were previously treated with standard therapy known to have a possible survival benefit or refused such therapy. The study will determine the safety of three dosage levels of Ad5 \[E1-, E2B-\]-CEA(6D) vaccine (phase I component), and the maximally tolerated dose of Ad5 \[E1-, E2B-\]-CEA(6D) vaccine (phase II component). The study drug is Ad5 \[E1-, E2B-\]-CEA(6D) given by subcutaneous (SQ) injection every 3 weeks for 3 immunizations. We will evaluate safety in each cohort at least 3 weeks after the last patient in the previous cohort has received their first injection. A dosing scheme will be considered safe if \<33% of patients treated at a dosage level experience DLT (e.g., 0 of 3, ≤1 of 6, ≤3 of 12 or ≤5 of 18 patients). We are currently enrolling up to 10 additional patients (Cohort 6) to evaluate safety, immunogenicity, and efficacy at the highest dose of vaccine.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Cohort 1
Cohort 1: Ad5 \[E1-, E2b-\]-CEA(6D) at a dose of 1 x 10\^9 particles
Intervention: Ad5 CEA Vaccine
Cohort 2
Cohort 2: Ad5 \[E1-, E2b-\]-CEA(6D) at a dose of 1 x 10\^10 particles
Intervention: Ad5 CEA Vaccine
Cohort 3
Cohort 3: Ad5 \[E1-, E2b-\]-CEA(6D) at a dose of 1 x 10\^11 particles
Intervention: Ad5 CEA Vaccine
Cohort 4
Cohort 4 (Phase II Cohort at MTD): Ad5 \[E1-, E2b-\]-CEA(6D) at a dose of 1 x 10\^11 particles
Intervention: Ad5 CEA Vaccine
Cohort 5
Cohort 5: Ad5 \[E1-, E2b-\]-CEA(6D) at a dose of 5 x 10\^11 particles
Intervention: Ad5 CEA Vaccine
Cohort 6
Cohort 6: Ad5 \[E1-, E2b-\]-CEA(6D) at a dose of 5 x 10\^11 particles
Intervention: Ad5 CEA Vaccine
Outcomes
Primary Outcomes
Number of Participants With Dose Limiting Toxicities
Time Frame: Every 3 weeks for 9 weeks and every 3 months for 1 year
The primary objective of this protocol is to determine the safety of immunization with Ad5 \[E1-, E2b-\]-CEA(6D) in patients with advanced or metastatic CEA-expressing malignancies. A dosing scheme will be considered safe if \<33% of patients treated at a dosage level experience DLT (e.g., 0 of 3, ≤1 of 6, ≤3 of 12 or ≤5 of 18 patients).
Number of Participants With Adverse Events
Time Frame: from the time of first dose to the 30 days past last dose of study drug, up to 330 days
Secondary Outcomes
- Clinical Response Rate(from first dose up to a year follow up)
- Immune Response Against CEA - IFN-gamma Secreting Cells by Visit(Baseline (Week 0) up to Week 9)
- CEA Antibody (ng/mL) by Visit(Baseline (Week 0) to Week 9)