We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Binary Oncolytic Adenovirus in Combination With HER2-Specific Autologous CAR VST, Advanced HER2 Positive Solid Tumors (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 : Recruiting
First Posted : November 14, 2018
Last Update Posted : August 29, 2022
The Methodist Hospital Research Institute
Information provided by (Responsible Party):
Daniel Wang, Baylor College of Medicine

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.

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

Show Show detailed description

Layout table for study information
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
Actual Study Start Date : December 14, 2020
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

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
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

  1. Histologically confirmed advanced refractory HER2 positive solid tumors, including but not limited to: head and neck squamous cell carcinoma; cancer of the salivary glands; lung cancer; breast cancer; bladder cancer; gastric cancer; esophageal cancer; colorectal cancer; and pancreatic adenocarcinoma. HER2 positivity is defined as ≥2+ staining by IHC with either the FDA-approved CB11 antibody (Leica) or anti HER2/neu (4B5) (VENTANA), which refers to greater than weak-to-moderate staining intensity in >10% tumor cells (HER2 positivity requirement is excluded in DL1 and DL2 as HER2 targeted agents are not used).
  2. The disease must be deemed unsuitable for curative treatments including surgery, radiotherapy, systemic therapy, including checkpoint inhibitors, or any combination of the above modalities by the referring oncology physician and confirmed by the senior oncologists leading the protocol.
  3. Disease must have progressed after standard first line therapy, or without available effective treatment options. Patients are still eligible if they have failed more than one line of therapy.
  4. The patient must have at least one tumor site appropriate for intratumoral injection.
  5. The patient must have radiographically measurable disease as per RECIST 1.1.
  6. The patient must have adequate organ function within 7 days prior to treatment as indicated by following measures:

    • Hematologic: Absolute neutrophil count (ANC) ≥1.0 x 109/l; Hemoglobin ≥9 g/dl; Platelet count ≥ 100 x 109/l; PT or PTT ≤ 1.5 x ULN unless the subject is receiving anticoagulation.
    • Hepatic function: bilirubin < 2 x ULN, and AST and ALT < 3 x ULN
    • Renal Function: serum creatinine <2 x the ULN or creatinine clearance >60 mL/min.
  7. Prior HER2 targeted therapy is allowed if delivered at least 4 weeks prior to the enrollment. (Excluding DL1 and DL2)
  8. Eastern Cooperative Oncology Group (ECOG) performance status 2 or less (Appendix I).
  9. Females of childbearing potential must have a negative pregnancy test and agree to use contraception during on-study protocol therapy, or deemed to be not able to get pregnant.
  10. Male subjects with pregnant partner/female partner of childbearing potential agree to use barrier contraceptive during the study to minimize the risk of embryo-fetal exposure.
  11. The patient is ≥ 18 years of age, and able to understand and give informed consent to study related procedures and treatments.

Exclusion Criteria:

  1. Patients with any concurrent treatment that would compromise the study including but not limited to continuous high dose corticosteroids (more than 10mg/day prednisone or equivalent dose), lympho-depleting antibodies, immunotherapy, targeted therapies or cytotoxic agents, CNS metastasis requiring continuous high-dose steroids (more than 10mg/day prednisone or equivalent dose) or other active therapeutic intervention. This does not include stable, previously-treated brain metastases. Patients on DL1 and DL2 can continue prior checkpoint inhibitors and HER2 targeted agents during the DLT evaluation period.
  2. Patients at significant risk of airway compromise or other critical obstruction (e.g. bowel, ureter, etc.) in the event of possible post injection tumor inflammation based on the investigative team's judgement.
  3. History or evidence of active autoimmune disease requiring continuous systemic corticosteroids, immunosuppressants or other disease modifying agents.
  4. Evidence of significant immunosuppressive conditions, such as the following:

    • Post organ transplant.
    • Diagnosis of HIV or other immunodeficiency disorders.
  5. Diagnosis of other malignancies within 5 years except for cutaneous basal cell or squamous cell carcinoma, well-differentiated thyroid cancer, or localized prostate or cervical cancer.
  6. Patients with known active infectious disease, such as hepatitis B or C infection.
  7. Patient has had acute myocardial infarction within 6 months prior to enrollment for treatment.
  8. Patients with abnormal left ventricular function (LVEF <55%).
  9. Injectable tumor site is considered to incur a significant risk of major hemorrhage (e.g. located in the CNS (brain), pulmonary parenchyma, and proximal to critical neurovascular structures).
  10. Pregnant or breastfeeding females.
  11. 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.

Information from the National Library of Medicine

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

Layout table for location contacts
Contact: Daniel Wang, MD 713 798-3750 danielw@bcm.edu
Contact: Jun Zhang 281-889-7394 jzhang22@houstonmethodist.org

Layout table for location information
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   
Sponsors and Collaborators
Baylor College of Medicine
The Methodist Hospital Research Institute
Layout table for investigator information
Principal Investigator: Daniel Wang, MD Baylor College of Medicine
Layout table for additonal information
Responsible Party: Daniel Wang, Assistant Professor, Center for Cell and Gene Therapy, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT03740256    
Other Study ID Numbers: H-43405 VISTA
First Posted: November 14, 2018    Key Record Dates
Last Update Posted: August 29, 2022
Last Verified: August 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Daniel Wang, Baylor College of Medicine:
Human Epidermal Growth Factor Receptor 2
Head and Neck Squamous Cell Carcinoma
Salivary Gland
Solid Tumor
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Salivary Gland Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Mouth Neoplasms
Mouth Diseases
Stomatognathic Diseases
Salivary Gland Diseases