Binary Oncolytic Adenovirus in Combination With HER2-Specific Autologous CAR VST, Advanced HER2 Positive Solid Tumors (VISTA)
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|ClinicalTrials.gov Identifier: NCT03740256|
Recruitment Status : Not yet recruiting
First Posted : November 14, 2018
Last Update Posted : January 23, 2020
This study is a first in human Phase 1 study that involves patients with a type of cancer called HER2 (Human Epidermal Growth Factor Receptor 2) positive cancer. Because there is no standard treatment for this cancer at this time or because the currently used treatments do not work fully, this study asks patients to volunteer to take part in a research study investigating the safety and efficacy of using special immune cells called HER2 chimeric antigen receptor-modified Adenovirus-specific cytotoxic T lymphocytes (HER2 specific CAR T cells), in combination with intra-tumor injection of CAdVEC, an oncolytic adenovirus that is designed to help the immune system including HER2 specific CAR T cell react to the tumor. The study is looking at combining these two treatments together, because we think that the combination of treatments will work better than each treatment alone. We also hope to learn the best dose level of the treatments and whether or not it is safe to use them together.
This research study combines two different ways of fighting cancer: oncolytic adenovirus (CAdVEC) and (HER2- specific autologous CAR T).
CAdVEC is an oncolytic adenovirus that has been modified to include additional immune system stimulators. Specifically, genes that stimulate the immune system have been added to the oncolytic adenovirus. Oncolytic adenoviruses are viruses that are made to target and kill cancer cells without killing normal cells. In this study, CAdVEC will be injected into participants tumor at one tumor site which is most easiest to reach. Once the oncolytic adenovirus infects the cancer cells, activation of the immune response will occur so it can attack and kill cancer cells. This approach may have limited effects on the other tumor sites that have not received the oncolytic virus injection, so, patients will also receive specific T cells following the intratumor CAdVEC injection. These T cells are special infection-fighting blood cells that can kill cells infected with viruses and tumor cells. Investigators have found from previous research that they can put a new gene into T cells and make them specifically recognize and kill cancer cells expressing HER2. Only patients that have already signed a consent form that allowed us to put on their T cells the HER2 chimeric receptor with viral antigen receptor on their T cells will be able to be in this study.
Investigators want to see if these cells can survive in the blood and affect the tumor. Both CAdVEC and HER2-specific autologous CAR T are investigational products. They are not approved by the FDA.
|Condition or disease||Intervention/treatment||Phase|
|Bladder Cancer Head and Neck Squamous Cell Carcinoma Cancer of the Salivary Gland Lung Cancer Breast Cancer Gastric Cancer Esophageal Cancer Colorectal Cancer Pancreatic Adenocarcinoma||Biological: CAdVEC||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||39 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A First in Human Phase I Trial of Binary Oncolytic Adenovirus in Combination With HER2-Specific Autologous CAR T Cells in Patients With Advanced HER2 Positive Solid Tumors|
|Estimated Study Start Date :||June 1, 2020|
|Estimated Primary Completion Date :||January 1, 2024|
|Estimated Study Completion Date :||January 1, 2038|
Experimental: Treatment Phase
Six dose levels will be evaluated using the BOIN design. Cohorts of size 3 will be enrolled at each dose level until 9 evaluable patients have been studied at a single dose. Each patient will receive an intratumoral injection of CAdVEC alone or combined with an injection of HER2.CAR.T cells 3 days later (Day 4), according to the following dose levels.
Dose Level 1 CAdVEC = 1.00E+10 HER2-specific-CAR- T = 0
Dose Level 2 CAdVEC = 1.00E+10 HER2-specific-CAR- T = 1.00E+06
Dose Level 3 CAdVEC = 1.00E+11 HER2-specific-CAR- T = 1.00E+06
Dose Level 4 CAdVEC = 1.00E+11 HER2-specific-CAR- T= 1.00E+07
Dose Level 5 CAdVEC = 1.00E+12 HER2-specific-CAR- T = 1.00E+07
Dose Level 6 CAdVEC = 1.00E+12 HER2-specific-CAR- T = 1.00E+08
The intratumoral administration of CAdVEC will create a pro-inflammatory tumor microenvironment and will promote the recruitment and expansion of adoptively transferred HER2 specific CAR T cells via CAR (tumor antigen). We expect HER2 CAR T cells expanded at primary tumor sites will re-circulate and target metastasized tumors. The combination we propose to test has the potential to overcome each of the established individual limitations of oncolytic viruses and of CAR T-cells. Testing each element separately would not be beneficial or informative, since the combination therapy is anticipated to have unique profiles of both therapeutic benefit and potential toxicities.
Other Name: HER2-specificCAR- T
- Number of patients with dose limiting toxicity (DLT) by CTCAE 5.0 [ Time Frame: 6 weeks after the HER2.CAR AdVST infusion or 6 weeks + 3 days after the CAdVEC injection. ]Incidence of dose limiting toxicities (DLT) of CAdVEC intratumoral injection in combination with HER2.CAR AdVST cells in patients with advanced refractory HER2 positive solid tumors.
- Overall Response Rate (ORR) according to RECIST1.1 criteria [ Time Frame: 13 weeks ]Overall response rate is defined as the number of patients experiencing PR or better (i.e. PR + CR) divided by the number evaluable for efficacy. Tumor regression or progression will be evaluated accordingly with RECIST 1.1 criteria.
- Disease Control Rate (DCR) [ Time Frame: 13 weeks ]Disease Control Rate is defined as as the number of patients experiencing SD or better (i.e. SD+PR+CR) divided by the number evaluable for efficacy. Tumor regression or progression will be evaluated accordingly with RECIST 1.1 criteria.
- Progression Free Survival (PFS) [ Time Frame: 15 years ]Progression-Free Survival is defined as the time from start of treatment to disease progression or death.
- Overall Survival (OS) [ Time Frame: 15 years ]Overall survival is defined as the time from the start of treatment to death due to any cause.
- Number of treatment related adverse events with grade 3 or greater severity by CTCAE 5.0 [ Time Frame: 30 days ]Treatment related adverse events with grade 3 or greater severity by CTCAE 5.0
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03740256
|Contact: Andrew Sikora, MD||713-798-3909||Andrew.Sikora@bcm.edu|
|Principal Investigator:||Andrew Sikora, MD||Baylor College of Medicine|