RECRUITING

Binary Oncolytic Adenovirus in Combination With HER2-Specific Autologous CAR VST, Advanced HER2 Positive Solid Tumors

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2020-12-14

Study Completion:2038-12-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03740256

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
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 ≥7 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.	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.

Inclusion Criteria

Exclusion Criteria

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 ≥7 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.

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.

Contacts and Locations

Study Contact

Shalini Makawita, MD

CONTACT

832-957-6500

Shalini.Makawita@bcm.edu

Jun Zhang

CONTACT

281-889-7394

jzhang22@houstonmethodist.org

Principal Investigator

Shalini Makawita, MD

PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Study Locations (Sites)

Baylor St. Luke's Medical Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Baylor College of Medicine

Shalini Makawita, MD, PRINCIPAL_INVESTIGATOR, Baylor College of Medicine

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-12-14

Study Completion Date2038-12-30

Study Record Updates