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.
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 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.
In this study, CAdVEC will be injected into participants tumor at one tumor site which is most easiest to reach. Once it 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 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 Solid Tumor | Biological: CAdVEC | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 45 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 2021 |
Estimated Primary Completion Date : | December 30, 2024 |
Estimated Study Completion Date : | December 30, 2038 |
Arm | Intervention/treatment |
---|---|
Experimental: Treatment Phase
Seven 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 = 5.00E+9 HER2 specific CAR-T cells = 0 Dose Level 2 CAdVEC = 1.00E+10 HER2 specific CAR-T cells = 0 Dose Level 3 CAdVEC = 1.00E+10 HER2 specific CAR-T cells = 1.00E+06 Dose Level 4 CAdVEC = 1.00E+11 HER2 specific CAR-T cells = 1.00E+06 Dose Level 5 CAdVEC = 1.00E+11 HER2 specific CAR-T cells = 1.00E+07 Dose Level 6 CAdVEC = 1.00E+12 HER2 specific CAR-T cells = 1.00E+07 Dose Level 7 CAdVEC = 1.00E+12 HER2 specific CAR-T cells = 1.00E+08 |
Biological: CAdVEC
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
|
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
This study will look at solid tumors (as a basket trial for any solid cancer) with HER2 positivity based on IHC
The patient must have adequate organ function within 7 days prior to consent for treatment as indicated by following measures:
Exclusion Criteria:
Evidence of significant immunosuppressive conditions, such as the following:
j. Pregnant or breastfeeding females. k. Uncontrolled intercurrent illness including but not limited to psychiatric illness and or social situations that in the opinion of the investigator would compromise compliance of study requirements or put the patient at unacceptable risk.
Contact: Daniel Wang, MD | 713 798-3750 | danielw@bcm.edu | |
Contact: Jun Zhang | 281-889-7394 | jzhang22@houstonmethodist.org |
United States, Texas | |
Baylor St. Luke's Medical Center | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Daniel Wang 713-798-3750 daniel.wang2@bcm.edu |
Principal Investigator: | Daniel Wang, MD | Baylor College of Medicine |
Tracking Information | |||||||||
---|---|---|---|---|---|---|---|---|---|
First Submitted Date ICMJE | November 9, 2018 | ||||||||
First Posted Date ICMJE | November 14, 2018 | ||||||||
Last Update Posted Date | April 26, 2021 | ||||||||
Estimated Study Start Date ICMJE | June 2021 | ||||||||
Estimated Primary Completion Date | December 30, 2024 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
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.
|
||||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
|
||||||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Binary Oncolytic Adenovirus in Combination With HER2-Specific Autologous CAR VST, Advanced HER2 Positive Solid Tumors | ||||||||
Official Title ICMJE | 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 | ||||||||
Brief Summary |
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. 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 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. In this study, CAdVEC will be injected into participants tumor at one tumor site which is most easiest to reach. Once it 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 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. |
||||||||
Detailed Description |
Treatment with CAdVEC: On the first day of your treatment, participants will receive an injection of CAdVEC into your tumor. A blood sample will be obtained from the participant before the CAdVEC intratumor injection . Depending on the location of the tumor, different techniques can be used for the injection into your tumor. The most common route of injection is ultrasound-guided percutaneous (needle puncture in the skin) injection, but endoscopic (using a lighted, flexible instrument called an endoscope) ultrasound-guidance will be used for some patients as appropriate. Prior to percutaneous injection, participants may receive an anti-anxiety medicine to calm them down, to relieve muscle spasms, and provide sedation. If the participants tumor is injected during an endoscopic procedure, the procedure may be done under sedation. Treatment with HER2- specific autologous T Cells: Earlier the participant gave blood for us to make HER2 targeting cytotoxic T-lymphocytes (HER2- specific autologous T Cells). These cells are grown in the lab and frozen for participants. Invesitgators made the cells by combining dendritic cells (DCs) or monocytes with the T cells in the presence of produced mixtures of adenoviral proteins. Investigators then put a new gene in to those T cells to make them specifically attract to and kill HER2 positive tumors. As the T cells grow, they are cultured by adding adenoviral proteins for stimulation and expansion. Investigators call those T cells: HER2- targeting T cells (HER2- specific autologous T Cells). This study looks at different doses of HER2- specific autologous T Cells. The decision about the dose participants receive is determined when enrolled on the study. Seven dose levels will be evaluated. 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. CAdVEC intratumoral injection will be given as a single injection to a single appropriate tumor site by direct, endoscopic, or image-guided injection on Day 1. The injection site will be chosen based on a combination of criteria, including accessibility and safety of injection site; tumor size; and anticipated tumor viability (e.g. avoid necrotic or cystic injection sites). HER2.CAR T cells will be given intravenously on day 4 after CAdVEC injection, with a 3 day window (until day 7). Before receiving the T cell infusion, participants may be given Benadryl (diphenhydramine) and Tylenol (acetaminophen). Tylenol and Benadryl are given to prevent a possible allergic reaction to the T cell administration. Standard medical tests before treatment: Before being treated, participants will receive a series of standard medical tests and procedures as well as research blood draws. Standard Medical tests during and after treatment: During treatment, participants will receive standard medical tests and procedures as well as research blood draws. Study specific evaluations: Investigators will follow participants closely after treatment for any side effects for at least 2 years after the last infusion. To learn more about the way the T cells are working in the body, an extra blood sample will be taken before the CAdVEC injection, before the CAR T cell infusion, and at week 1, 2, 4 , 6, months 3, 6, 9 and 12 after CAR T cell infusion. Thereafter every 6 months up to 5 years and then yearly for 15 years. Investigators will use this blood to see how long the T cells last and to look at the immune response to the cancer. Investigators may also ask to get a tumor tissue biopsy at week 12 if necessary. Buccal swabs (cheek scraping) and urine will be collected before CAdVEC injection, Days 2, 4 (or the day of CAR T-cell infusion), weeks 1 and 2 after CAR T cell infusion. |
||||||||
Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 1 | ||||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
||||||||
Condition ICMJE |
|
||||||||
Intervention ICMJE | Biological: CAdVEC
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
|
||||||||
Study Arms ICMJE | Experimental: Treatment Phase
Seven 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 = 5.00E+9 HER2 specific CAR-T cells = 0 Dose Level 2 CAdVEC = 1.00E+10 HER2 specific CAR-T cells = 0 Dose Level 3 CAdVEC = 1.00E+10 HER2 specific CAR-T cells = 1.00E+06 Dose Level 4 CAdVEC = 1.00E+11 HER2 specific CAR-T cells = 1.00E+06 Dose Level 5 CAdVEC = 1.00E+11 HER2 specific CAR-T cells = 1.00E+07 Dose Level 6 CAdVEC = 1.00E+12 HER2 specific CAR-T cells = 1.00E+07 Dose Level 7 CAdVEC = 1.00E+12 HER2 specific CAR-T cells = 1.00E+08 Intervention: Biological: CAdVEC
|
||||||||
Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||||
Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
45 | ||||||||
Original Estimated Enrollment ICMJE |
39 | ||||||||
Estimated Study Completion Date ICMJE | December 30, 2038 | ||||||||
Estimated Primary Completion Date | December 30, 2024 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria: This study will look at solid tumors (as a basket trial for any solid cancer) with HER2 positivity based on IHC
Exclusion Criteria:
j. Pregnant or breastfeeding females. k. Uncontrolled intercurrent illness including but not limited to psychiatric illness and or social situations that in the opinion of the investigator would compromise compliance of study requirements or put the patient at unacceptable risk. |
||||||||
Sex/Gender ICMJE |
|
||||||||
Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
|
||||||||
Listed Location Countries ICMJE | United States | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT03740256 | ||||||||
Other Study ID Numbers ICMJE | H-43405 VISTA | ||||||||
Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product |
|
||||||||
IPD Sharing Statement ICMJE | Not Provided | ||||||||
Responsible Party | Daniel Wang, Baylor College of Medicine | ||||||||
Study Sponsor ICMJE | Baylor College of Medicine | ||||||||
Collaborators ICMJE | The Methodist Hospital System | ||||||||
Investigators ICMJE |
|
||||||||
PRS Account | Baylor College of Medicine | ||||||||
Verification Date | April 2021 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |