Phase 1
Completed N=38
Safety and Tolerability of a Modified Vaccinia Ankara (MVA)-Based Vaccine Modified to Express Brachyury and T-cell Costimulatory Molecules (MVA-Brachyury-TRICOM)
Source: ClinicalTrials.gov NCT02179515 ↗Enrolled (actual)
38
Serious AEs
21.1%
Results posted
Jan 2021
Primary outcomePrimary: Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) — 3; 14; 17 Participants
Summary
Background:
- This cancer vaccine was developed to help teach the body's immune system to attack and destroy cancer cells. It teaches immune cells to target the Brachyury protein. This protein is present in some tumor cells, and it can help tumor cells spread to other parts of the body. Researchers want to see whether the new Brachyury protein vaccine can help treat people with advanced carcinomas.
Objective:
- To test the safety and effectiveness of giving the modified vaccinia Ankara (MVA)-brachyury-B7-1, ICAM-1 (Intercellular Adhesion Molecule 1), and LFA-3 (lymphocyte function-associated antigen 3) TRICOM vaccine to people with cancer.
Eligibility:
- Adults ages 18 and over whose type of cancer has not responded to standard therapies who do not have a history of autoimmune diseases and are capable of taking care of themselves.
Design:
* Participants will be screened with a medical history and physical exam. They will have blood and urine tests. They may have a computed tomography (CT) scan, a positron emission tomography (PET) scan, and a brain magnetic resonance imaging (MRI) scan. They may have a bone scan. They will have an electrocardiogram (ECG) to test heart rhythm.
* Participants will have visits about every 4 weeks. They will have a physical exam and blood and urine tests. They will be injected with the vaccine under the skin into the upper thigh or around the armpits.
* CT scans or MRI scans will be done at visit 1, after 3 months on study, and again 3 months later if still on the study. Another ECG will be done at their last vaccine visit.
* When participants stop the vaccine, they will return for visits until they recover from any side effects. They will have tests including physical exam, blood tests, scans, and x-rays.
* Participants will be asked to enroll in another study for long-term follow-up.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) |
3; 14; 17 | — |
| PRIMARY Number of Participants With Dose-Limiting Toxicities (DLT) |
0; 0; 0 | — |
| PRIMARY Maximum Tolerated Dose (MTD) |
NA | — |
| PRIMARY Number of Participants With Grade 3 or Greater Adverse Events Possibly Related to Vaccine |
0; 1; 0 | — |
| SECONDARY Number of Participants With Brachyury-Specific T-cell Responses Developed After 1, 2, and 3 Vaccinations |
0; 4; 0; 1; 2; 1 | — |
| SECONDARY Percentage of Total Peripheral Blood Mononuclear Cells (PBMCs) in Peripheral Blood Before Vaccination, and After 1 and 3 Vaccinations |
24.31; 32.64; 32.89; 23.68; 34.99; 29.86 | — |
| SECONDARY Number of Participants With Positive Anti-Brachyury Antibodies |
0; 1; 2; 0; 1; 3 | — |
| SECONDARY Changes in Serum Cytokines Soluble CD27 (sCD27) and Soluble Factors |
20.53; 19.34; 12.10; 25.65; 18.40; 15.12 | — |
| SECONDARY Changes in Serum Cytokines Soluble CD40 Ligand (sCD40L) and Soluble Factors |
4.76; 17.52; 18.94; 17.11; 17.81; 16.05 | — |
| SECONDARY Changes in the Ratio of Serums Soluble CD27 (sCD27):Soluble CD40 Ligand (sCD40L) |
4.31; 1.02; 0.64; 1.50; 1.25; 0.82 | — |
| SECONDARY Changes in Serum Cytokines Interleukin 2 (IL2), Interleukin 4 (IL4), Interleukin 10 (IL10), and Interferon Gamma (IFNg) |
0.00; 0.00; 0.00; 0.00; 0.00; 0.00 | — |
Eligibility Criteria
- INCLUSION CRITERIA:
(All Subjects)
- Patients must have a metastatic or unresectable locally advanced malignant solid tumor, histologically confirmed by the Laboratory of Pathology, National Cancer Institute (NCI). In the case of chordoma, unresectable, locally recurrent, or metastatic tumors are acceptable for enrollment, given that this represents incurable disease. Efforts will be made, as much as possible, to enroll patients with tumor types with known increased expression of brachyury (such as lung, breast, ovarian, prostate, colorectal, pancreatic, or chordoma; other tumors may be included as data on the level of brachyury in those tumors becomes available).
- Patients may have measurable or nonmeasurable but evaluable disease. Patients with surgically resected metastatic disease at high risk of relapse are also eligible.
- Prior therapy: Patients must have completed or had disease progression on at least one prior line of disease-appropriate therapy for metastatic disease, or not be candidates for therapy of proven efficacy for their disease.
- There should be a minimum of 4 weeks from any prior chemotherapy, immunotherapy and/or radiation, with the exception of hormonal therapy for prostate and breast cancers, human epidermal growth factor receptor 2 (HER2)-directed therapy for HER2+ breast cancer (3+ immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH+), and erlotinib in epidermal growth factor receptor (EGFR)-mutated lung cancer in the expansion cohort as detailed in section. There should be a minimum of 6 weeks from any prior antibody therapies, (such as ipilimumab or anti-Programmed cell death protein 1 (PD1)/Programmed death-ligand 1 (PDL1) due to prolonged half-life.
- Patients must have recovered (grade 1 or baseline) from any clinically significant toxicity associated with prior therapy. Typically, this is 3-4 weeks for patients who most recently received cytotoxic therapy, except for the nitrosoureas and mitomycin C, for which 6 weeks is needed for recovery.
- Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of modified vaccinia Ankara (MVA)-brachyury-B7-1, ICAM-1 (Intercellular Adhesion Molecule 1), and LFA-3 (lymphocyte function-associated antigen 3) TRICOM vaccine in patients 90% on room air.
- The effects of MVA-brachyury-TRICOM on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for a period of 4 months after the last vaccination therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Patients with prostate cancer must continue to receive gonadotropin releasing hormone (GnRH) agonist therapy (unless orchiectomy has been done). If a patient has refused GnRH therapy, they may be enrolled on a dose level for which the safety has already been determined.
Patients must be able to understand and be willing to sign a written informed consent document.
INCLUSION CRITERIA
(Expansion Phase Only)
The following inclusion criteria apply specifically to patients being considered for the expansion phase of the protocol.
- Subjects with epidermal growth factor receptor (EGFR)-mutated lung cancer may continue erlotinib if they have been on the drug for greater than or equal to 3 months with stable disease or a response. Erlotinib may also be continued in the case of a progressing tumor after prior response (or > 6 months stable disease).
- Patients with Estrogen receptor positive (ER+) breast cancer being treated with hormonal therapy (selective estrogen receptor modulator or aromatase inhibitor) who have rising tumor markers as evidence of disease progression or metastatic disease o
Data sourced from ClinicalTrials.gov (NCT02179515). 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. Informational only — not medical advice.