Binary Oncolytic Adenovirus in Combination With HER2-Specific CAR VST, Advanced HER2 Positive Solid Tumors (VISTA) (VISTA)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03740256|
Recruitment Status : Not yet recruiting
First Posted : November 14, 2018
Last Update Posted : November 29, 2018
This study 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-AdVST), in combination with intra-tumor injection of CAdVEC, an oncolytic adenovirus that is designed to help the immune system including HER2-AdVST react to the tumor.
The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: oncolytic adenovirus (CAdVEC) and T cells (HER2-AdVST).
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. Other oncolytic adenoviruses have been used in patients before however CAdVEC has not. 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, the genes will be expressed, resulting in activation of the immune response so it can attack and kill cancer cells. However, because this approach may have limited effects on the other tumor sites that have not received the oncolytic virus injection, 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 investigators can put a new gene into T cells and make them specifically recognize and kill cancer cells expressing HER2. In the past patients have 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. Investigators want to see if these cells can survive in a patients blood and affect the tumor. Although HER2 chimeric antigen receptor modified cytotoxic T lymphocytes have been used in patients before, HER2-AdVST has not.
|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|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||39 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||VISTA (VIrus Specific T Cells and Adenovirus): A First in Human Phase I Trial of Binary Oncolytic Adenovirus in Combination With HER2-Specific CAR VST Cells in Patients With Advanced HER2 Positive Solid Tumors|
|Estimated Study Start Date :||January 1, 2019|
|Estimated Primary Completion Date :||January 1, 2023|
|Estimated Study Completion Date :||January 1, 2037|
Experimental: Treatment Phase
Six dose levels will be evaluated using the BOIN design. Cohorts of size 3 will be enrolled at each dose level (see section 11.1) 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.AdVST 3 days later (Day 4), according to the following dose levels.
Dose Level 1 CAdVEC = 1.00E+10 HER2.CAR-AdVST = 0
Dose Level 2 CAdVEC = 1.00E+10 HER2.CAR-AdVST = 1.00E+06
Dose Level 3 CAdVEC = 1.00E+11 HER2.CAR-AdVST = 1.00E+06
Dose Level 4 CAdVEC = 1.00E+11 HER2.CAR-AdVST = 1.00E+07
Dose Level 5 CAdVEC = 1.00E+12 HER2.CAR-AdVST = 1.00E+07
Dose Level 6 CAdVEC = 1.00E+12 HER2.CAR-AdVST = 1.00E+08
The administration of CAdVEC may create a pro-inflammatory tumor microenvironment and will promote the recruitment and expansion of adoptively transferred CAR AdVSTs via both CAR recognition of tumor antigen and TCR recognition of viral antigen. The CAR AdVSTs expanded at primary tumor sites may re-circulate and target metastasized tumors. The combination this study proposes to test has the potential to overcome each of the established individual limitations of oncolytic viruses and of CAR T-cell/VST and testing each element separately would not be beneficial or informative.
Other Name: HER2.CAR AdVST
- 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||Texas Children's Hospital|