Neoplasms

All Conditions

Mouth and Tooth Diseases

Rare Diseases

Carcinoma

Salivary Gland Neoplasms

Carcinoma, Adenoid Cystic

Mouth Neoplasms

Head and Neck Neoplasms

Mouth Diseases

Stomatognathic Diseases

Salivary Gland Diseases

Adenoid Cystic Carcinoma

Oral Cancer

All Drugs and Chemicals

Gallium 68 PSMA-11

Radiopharmaceuticals

On the scheduled visit date for the study,

* An intravenous cannula (plug) will be inserted in a vein in the participant's arm, through which the 68-Ga PSMA radiotracer for the scan will be injected. The infusion will take about 1-2 minutes.
* PET imaging will be performed with a dedicated PET/CT scanner. 2.5-6.0 mCi (depending on weight of the patient) of PSMA radiotracer will be injected intravenously.

68-Ga PSMA PET scan

Dr Wen-Long NEI, MD

The objectives of this pilot feasibility study, which is on the use of 68-Ga PSMA PET imaging of salivary gland tumours, are

* to determine the proportion of patients with high PSMA-ligand uptake on Ga-68 PSMA imaging in locally advanced, recurrent or metastatic salivary gland cancers and other rare cancer; and
* to determine if in vitro PSMA expression correlates to PSMA-ligand uptake on Ga-68 PSMA imaging in locally advanced, recurrent or metastatic salivary gland cancers and other rare cancers.

The hypotheses of this study are that there is high PSMA-ligand uptake on Ga-68 PSMA imaging in locally advanced, recurrent or metastatic salivary gland cancers and other rare cancers; and that in vitro PSMA expression correlates to PSMA-ligand uptake on Ga-68 PSMA imaging.

The potential participant will be screened and confirmed for eligibility by the appropriate study-team member. A signed IRB approved informed consent will be obtained prior to conducting any study-related procedures.

On the scheduled visit date for the study,

* An intravenous cannula (plug) will be inserted in a vein in the participant's arm, through which the 68-Ga PSMA radiotracer for the scan will be injected. The infusion will take about 1-2 minutes.
* PET imaging will be performed with a dedicated PET/CT scanner. 2.5-6.0 mCi (depending on weight of the patient) of PSMA radiotracer will be injected intravenously.
* A PET scan will be done around 60 minutes after the injection of the 68-Ga PSMA imaging agent.
* During imaging, the participant will be asked to lie still and may be asked to hold his/her breath for a few seconds.
* Imaging will be performed using a PET/CT, which will take 30 to 40 minutes to complete. Imaging of the body from vertex to mid thigh or feet will be obtained.
* After the completion of the scan, the plug will be removed.

A Final Study Visit will take place on that one scheduled day. The participant will not need to visit the doctor's office during the course of the study outside of their usual scheduled doctor's follow up appointments.

PSMA-PET Imaging of Salivary Gland Tumours and Other Rare Cancers

The proportion of patients with PSMA-ligand uptake greater than liver uptake on Ga-68 PSMA imaging in locally advanced, recurrent or metastatic salivary gland cancers and other rare cancer.

Correlation between the value of IHC PSMA expression and the PSMA PET SUVmax in locally advanced, recurrent or metastatic salivary gland cancers and other rare cancers.

National Cancer Centre, Singapore

Infections

Xerostomia

Adenoviridae Infections

Gene Transfer

AdhAQP1

Blake M Warner, D.D.S.

This study will examine whether the experimental drug AdhAQP1 can increase salivary flow in patients whose parotid glands have been exposed to therapeutic radiation for treatment of head and neck cancer. Radiation may damage the parotid glands (salivary glands located under the skin in front of the ear), leading to dry mouth, infections, excessive tooth decay, mouth sores, difficulty swallowing and pain. AdhAQP1 contains the human aquaporin-1 gene, which codes for a protein that works to transport water across cells, and a virus that normally can cause colds in humans, but is modified to render it ineffective. In animal experiments, AdhAQP1 has increased saliva production for a short time.

Patients between 18 years of age or older who received radiation treatment for head and neck cancer at least 5 years before enrolling in this study, who have no evidence of recurrent tumor, who have dry mouth and who secrete abnormally low levels of saliva from the parotid glands may be eligible for this study. Candidates are screened with a medical history, physical examination, blood, urine and saliva tests, electrocardiogram (EKG), chest x-ray, MRI exam, gallium scan (a nuclear medicine test to look for inflammation in the salivary glands), technetium pertechnetate scan (a nuclear medicine test to examine salivary gland function), parotid sialogram (x-ray of parotid gland), PET and CT scans to look for signs of tumor and a skin biopsy to collect skin cells for use in immunological tests.

Participants have a salt and sugar solution infused through a catheter (plastic tube) into both parotid glands. After 10 minutes, the solution drains into the mouth and is swallowed. Saliva is collected from the parotid glands at 6 and 24 hours after administration of the salt and sugar solution. Ten to 14 days later, patients are admitted to the NIH Clinical Center for up to 4 days for the following tests and procedures:

* On the first day, administration, through a catheter, of the study drug AdhAQP1 into one parotid gland.
* Monitoring over the next 3 days for changes in patients' ability to produce saliva. This includes medical examinations and several blood, urine and saliva collections.
* Technetium scan on day 2.
* Gallium scan on day 2.

Patients return to NIH for follow-up visits at 1, 2, 4, and 6 weeks after the AdhAQP1 infusion and then 3, 4, 5, 6 and 12 months for a medical examination and blood, urine and saliva collections. Gallium, technetium and MRI scans are repeated at several of the follow-up visits, and sialograms are done at 6 and 12 months. Chest x-ray and EKG are repeated at 4 and 6 months.

The treatment of most head and neck cancer patients includes ionizing radiation (IR). Salivary glands in the IR field suffer irreversible damage. There is no conventional treatment available to correct this condition. Our research group has been developing the AdhAQP1 recombinant serotype 5 adenoviral (rAd5) vector based on the hypothesis that a replication deficient rAd5 vector is capable of safely transferring the human aquaporin-1 (hAQP1) cDNA to parotid glands of adult patients with IR-induced salivary hypofunction, resulting in an elevated salivary output, albeit transiently. Salivary glands have proven to be valuable gene transfer targets in numerous pre-clinical animal model studies. hAQP1, the archetypal water channel, is a plasma membrane protein that facilitates water movement across lipid bilayers. Rat and minipig studies have clearly shown that the AdhAQP1 strategy for restoring salivary flow to IR-damaged salivary glands is effective, and studies in rats, non-human primates and minipigs have shown that AdhAQP1 and similar rAd5 vectors are without significant untoward effects after salivary gland delivery. The purpose of this clinical protocol is to test the safety of AdhAQP1, with some measures of efficacy, in adult patients with established IR-induced parotid gland hypofunction. The targeted tissue site for the AdhAQP1 vector in the proposed study is a single parotid gland. In this Phase 1 dose-escalation study, safety will be evaluated using conventional clinical and immunological parameters. The primary outcome measure for biological efficacy will be parotid gland salivary output.

Effect of AdhAQP1 on Salivary Flow in Patients Treated With Radiation for Head and Neck Cancer

Open-Label, Dose-Escalation Study Evaluating the Safety of a Single Administration of AdhAQP1, an Adenoviral Vector Encoding Human Aquaporin-1 to One Parotid Salivary Gland in Individuals With Irradiation-Induced Parotid Salivary Hypofunction

National Institute of Dental and Craniofacial Research (NIDCR)

Salivary sample collection, quality of life survey, salivary gland imaging, bone marrow aspiration

collection of approximately 40 mL of bone marrow aspirate

Bone Marrow Aspiration

Salivary gland size will be measured by ultrasound.

Ultrasound Imaging of Salivary Glands

Whole saliva production rates (sialometry) will be measured under unstimulated (first passive drool method) and stimulated (chewing gum) saliva collection conditions

Salivary Assay

Participants will self-assess with the following Quality of Life (QoL) surveys: University of Michigan Xerostomia related quality of life scale (XeQOL), the MD Anderson Dysphagia Index (MDADI), and the VAS xerostomia questionnaire.

Quality of Life Instruments

Randall Kimple, PhD

Xerostomia, or dry mouth, is a common side effect of head neck radiation. Current treatment options for radiation-induced xerostomia are generally supportive in nature. Most of these supportive interventions do not reverse xerostomia and are palliative in intent.

The investigators propose that autotransplantation of marrow-derived mesenchymal stromal cells (MSCs) in salivary glands post-RT or post-chemoradiation therapy (CRT) may provide an innovative remedy to treat xerostomia and restore quality of life.

Participants can expect to be on study for up to 6 months.

This feasibility study will analyze the salivary composition, salivary viscoelasticity, salivary gland US, and QoL surveys of participants without head and neck cancer (HNC) to determine standard values. The investigators will then compare this to the salivary composition and viscoelasticity of participants with treated HNC.

Additionally, the investigators will examine the paracrine factors of marrow MSCs in order to prove a hypothesis that paracine factors constitutively expressed by marrow MSCs \[Wnts, fibroblast growth factors (FGFs), GDNF and others\] will directly influence the biology of dormant salivary gland stem cells following intraglandular transplantation and allow for functional recovery following RT.

Primary Objective

* To determine the feasibility of in vitro expansion of marrow-derived MSCs from HNC patients to \>50 million cells.

Secondary Objectives

* To assess the stability of salivary function in HNC patients using quality-of-life (QoL) questionnaires and salivary composition analysis.
* To assess the stability of salivary gland size as measured by ultrasound.

Correlative Objectives

* To compare assess the secretome profile of MSCs from HNC patients treated with radiation or, chemoradiation, or previously untreated.
* To compare the salivary composition, viscoelasticity, salivary gland ultrasound, and QoL of HNC patients to non-HNC patients

Salivary Gland Autotransplantation for Treatment of XRT Induced Xerostomia

Salivary Gland Autotransplantation of Marrow Mesenchymal Stromal Cells for Treatment of Radiation-induced Xerostomia - FDA IND (Investigational New Drug) Enabling Studies

The secretome profile of MSCs from HNC participants treated with radiation, chemoradiation, or previously untreated will be statistically compared using enzyme-linked immunosorbent assay (ELISA).

The secretome profile of MSCs from HNC participants treated with radiation, chemoradiation, or previously untreated will be statistically compared using and western blots.

The feasibility of in vitro expansion of MSCs derived from marrow aspirates collected from participants will be determined by if they can be culture expanded for up to two weeks to generate \>50 million MSCs per donor. Feasibility will reported as the number of participants whose marrow-derived MSCs can be expanded in vitro to \> 50 million cells within two weeks.

The University of Michigan Xerostomia related quality of life scale (XeQOL) is a 15-item questionnaire about how a participants oral health affects their life. Each item is scored from 1-5 either 'not at all', 'a little', 'somewhat', 'quite a bit', or 'very much' for a total score of 15-75. Higher scores represent greater degree of symptoms.

The MD Anderson Dysphagia Inventory (MDADI) is a 20-item questionnaire about how a participants perceive their swallowing ability. Each item is scored from 'strongly agree', 'agree', 'no opinion', 'disagree', or 'strongly disagree'. One question provides a 'global score between 1-5 where 1 is extremely low functioning and 5 is high functioning. The remaining 19 questions measure a composite score from 20-100 where higher scores represent higher degree of function.

The Visual Analogue Scale (VAS) - xerostomia questionnaire is an 8-item questionnaire about how a participant perceives their dry mouth. Each item is visually scored on a sliding scale (100mm in length) between two extremes (Q1 and Q2 from 'not difficult at all' to 'very difficult', Q3 from 'A lot' to 'None', Q4-Q7 from 'Not Dry at All' to 'Very Dry', and Q8 from 'Not Thirsty at All' to 'Very Thirsty'. The participant places a line on the scale to mark their answer. Change between various time points can be determined based on measured distance along the scale for each answer.

Unstimulated saliva production will be measured at two time points by the passive drool method over a 5-minute time frame. Participants will allow saliva to pool in the mouth and, then, with head tilted forward, gently guide saliva into a saliva collection aid attached to a cryovial. Difference in weight of the cryovial empty and after the test will represent the amount of saliva produced.

Stimulated saliva production will be measured at two time points by having participants chew inert gum base to the pace of a metronome (70 beats per minute) while expectorating saliva (without swallowing) into the saliva collection aid for 5 minutes total. Difference in weight of the cryovial empty and after the test will represent the amount of saliva produced.

The size of salivary glands will be measured via ultrasound at baseline and up to 6 months on study.

University of Wisconsin, Madison

Symptoms and General Pathology

Musculoskeletal Diseases

Eye Diseases

Skin and Connective Tissue Diseases

Immune System Diseases

Syndrome

Sjogren's Syndrome

Graft vs Host Disease

Arthritis

Arthritis, Rheumatoid

Joint Diseases

Rheumatic Diseases

Collagen Diseases

Dry Eye Syndromes

Keratoconjunctivitis Sicca

Lacrimal Apparatus Diseases

Connective Tissue Diseases

Autoimmune Diseases

Homologous Wasting Disease

This study will examine whether transplanted stem cells can turn into salivary gland cells in stem cell recipients. If so, stem cells might be used to restore salivary gland function in patients with Sjogren's syndrome and other causes of dry mouth. People with severe dry mouth may develop difficulty swallowing, severe tooth decay, infections of the mouth and pharynx, and mouth sores.

Female patients 18 years of age and older who are enrolled in the National Heart, Lung and Blood Institute's protocol 97-H-009 or 97-H-0202 and who have received a stem cell transplant from a male donor may be eligible for this study. Five patients with graft-versus host disease (GVHD) and five without GVHD will be included. GVHD is a transplantation reaction in which the donor's cells mount an immune response against the recipient's tissues. Patients with chronic GVHD have mouth ulcerations and dry mouth similar to that of patients with Sjogren's syndrome. Five healthy female volunteers will also be enrolled.

Participants will have a medical and dental history. Then, cells will be collected from the inside of the cheek (buccal cell scraping) and from the salivary glands (labial gland biopsy) as described below:

Buccal cell scraping - Cells are collected from the inside of the cheek by wiping for 5 seconds with a plastic brush.

Labial glands biopsy - The lower lip will be numbed and a small incision will be made on the inside of the lower lip. Six small salivary glands in the lower lip will be removed and the incision will be closed with four stitches.

Cells collected from these procedures will be examined to see if donated stem cells turned into salivary gland or cheek cells.

Patients will return to the clinic 5 to 10 days after the biopsy to have the stitches removed and assess healing.

Patients with Sjogren's syndrome (1-2 million in the U.S.), and patients exposed to ionizing radiation during therapy for head and neck cancer (\~40,000 new patients/year in the U.S.), experience severe salivary gland hypofunction. In both patient groups, via different pathogenic mechanisms, acinar cells in the glands are lost. These cells are the sole site of fluid production in salivary glands, and such patients cannot produce adequate levels of saliva, leading to considerable morbidity (xerostomia, dysphagia, dental caries, oro-pharyngeal infections, and mucositis). In many patients, all parenchymal tissue may be lost. For this latter group, there is no available therapy as they are not candidates for either pharmacological or gene therapy if little to no epithelial tissue remains. Recent reports suggest that organ-specific stem cells can differentiate into cells of other organs. These findings carry significant implications for possible clinical use. This protocol will investigate if adult human hematopoietic stem cells (HSC) can transdifferentiate into salivary gland and oral mucosal epithelial cells. We will recruit female bone marrow transplant recipients (from existing NHLBI protocols) who have received HSC from a male donor. This gender-mismatched strategy will allow us to detect cells of donor origin by using an RNA probe specific to the human Y chromosome. A biopsy of labial minor salivary glands and a cheek scraping will be obtained from female transplant patients. The biopsy causes minimal discomfort and the cheek scraping is a non-invasive technique. Both procedures are used routinely for clinical diagnosis. The samples will be co-stained for specific genetic and protein markers for salivary gland or oral mucosal epithelial cells, respectively. Cells positive for these markers (Y chromosome, cytokeratins, mucin 1, and NKCC1) would indicate that the donor's HSC became functionally competent salivary gland epithelial cells. This protocol will also examine bone marrow transplant recipients with chronic Graft-versus-Host Disease (GVHD). These patients show similar complications (xerostomia and oral mucositis) as those encountered in patients with Sjogren's Syndrome. We hypothesize that GVHD may provide a positive recruitment signal for HSC to home to salivary and oral mucosal sites. This protocol will recruit 5 female bone marrow transplant recipients without GVHD and 5 with GVHD. The primary potential benefit of this study is that if HSC can turn into salivary gland cells, they could be used to regenerate lost salivary gland tissues or to seed an artificial salivary gland for patients with irreversible salivary gland damage.

Potential of Transplanted Stem Cells to Mature Into Salivary Gland and Cheek Cells

Assessment of the Potential of Hematopoietic Stem Cells to Transdifferentiate Into Salivary Gland and Oral Mucosal Epithelial Cells in Adult Bone Marrow Transplant Patients

Nervous System Diseases

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Pituitary Diseases

Melanoma

Neuroendocrine Tumors

Glioma

Retinoblastoma

Sarcoma

Mesothelioma

Mesothelioma, Malignant

Osteosarcoma

Medulloblastoma

Neuroblastoma

Carcinoid Tumor

Rhabdomyosarcoma

Ocular Melanoma

Neuroendocrine Tumor

Soft Tissue Sarcoma

Malignant Mesothelioma

Pancreatic Neuroendocrine Tumor

Vasoconstrictor Agents

Respiratory System Agents

Hematinics

Epinephrine

Liver Extracts

Racepinephrine

Epinephryl borate

ENV-101 (taladegib) tablets, 200 mg once-daily in 28-day cycles

ENV-101 (taladegib) tablets, 300 mg once-daily in 28-day cycles

ENV-101 (taladegib)

Paul Frohna, M.D., Ph.D.

This study employs a 2-stage design that aims to evaluate the efficacy and safety of ENV- 101, a potent Hedgehog (Hh) pathway inhibitor, in patients with refractory advanced solid tumors characterized by loss of function (LOF) mutations in the Patched-1 (PTCH1) gene. Stage 1 of this study will enroll approximately 44 patients randomized between two dose levels. As appropriate, Stage 2 of the study will expand enrollment based on the results of Stage 1.

A Study Evaluating the Safety and Efficacy of ENV-101 (Taladegib) in Patients With Advanced Solid Tumors Harboring PTCH1 Loss of Function Mutations

A Phase 2, Multi-Center Study Evaluating the Safety and Efficacy of ENV-101 (Taladegib) in Patients With Advanced Solid Tumors Harboring PTCH1 Loss of Function Mutations

ORR is comprised of Complete Response (CR) and Partial Response (PR), measured by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1), as determined by an independent review (confirmed CR or PR will be defined as a repeat assessment performed no less than 28 days after the criteria for response is first met).

Unacceptable toxicities = non-hematologic AEs \>= Grade 3 in severity, not including alopecia and fatigue.

Best overall response of confirmed CR or PR as determined by the treating Investigator using RECIST 1.1.

CBR = the proportion of patients who achieved CR, PR or stable disease as determined by the treating Investigator using RECIST 1.1.

OS = Number of months from initiation of study medication to the date of death due to any cause or last follow up.

DOR = the number of months from the start of CR or PR, whichever response is recorded first and subsequently confirmed, to the first date that recurrent or progressive disease is documented or death.

PFS = number of months from initiation of study medication to the earlier of disease progression or death due to any cause or last follow up.

Percentage change in inhibition of Gli1, a marker for inhibition of the Hedgehog pathway, in skin biopsies.

Measurement of trough concentration of study medication in blood at Baseline and the end of each 28-day treatment cycle

Endeavor Biomedicines, Inc.

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Esophageal Neoplasms

Breast Neoplasms

Adenocarcinoma

Stomach Neoplasms

Carcinoma, Squamous Cell

Lung Neoplasms

Urinary Bladder Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Esophageal Cancer

Stomach Cancer

Mitogens

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

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.

CAdVEC

Shalini Makawita, MD

Jun Zhang

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.

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. Investigators 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. After receiving the CAdVEC injection participants will be observed for at least 4 hours before leaving the hospital. During that time the study team will monitor vital signs and watch for any side-effects from the treatment. Participants will also be contacted by telephone about 24 hours after receiving the CAdVEC injection.

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. After receiving the infusion of HER2-specific autologous T cells participants will be observed for at least 3 hours before they may leave the hospital. Additionally, participants must plan to remain in the Houston area for at least 3 weeks after the infusion.

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 obtain a tumor tissue biopsy before CAdVEC injection, between days 5 and 10 after infusion of the HER-2 CAR-T cells, and at the time tumor recurs. 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.

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

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

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 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 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 is defined as the time from start of treatment to disease progression or death.

Overall survival is defined as the time from the start of treatment to death due to any cause.

Treatment related adverse events with grade 3 or greater severity by CTCAE 5.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PSMA-PET Imaging of Salivary Gland Tumours and Other Rare Cancers	NCT05581979	Salivary Gland ... Rare Malignant ...	68-Ga PSMA PET ...	21 Years - 99 Years	National Cancer Centre, Singapore
Effect of AdhAQP1 on Salivary Flow in Patients Treated With Radiation for Head and Neck Cancer	NCT00372320	Parotid Salivar...	Gene Transfer AdhAQP1	18 Years -	National Institutes of Health Clinical Center (CC)
Effect of AdhAQP1 on Salivary Flow in Patients Treated With Radiation for Head and Neck Cancer	NCT00372320	Parotid Salivar...	Gene Transfer AdhAQP1	18 Years -	National Institutes of Health Clinical Center (CC)
Salivary Gland Autotransplantation for Treatment of XRT Induced Xerostomia	NCT04007081	Xerostomia Head and Neck C...	Bone Marrow Asp... Ultrasound Imag... Salivary Assay Quality of Life...	18 Years - 89 Years	University of Wisconsin, Madison
Salivary Gland Autotransplantation for Treatment of XRT Induced Xerostomia	NCT04007081	Xerostomia Head and Neck C...	Bone Marrow Asp... Ultrasound Imag... Salivary Assay Quality of Life...	18 Years - 89 Years	University of Wisconsin, Madison
Potential of Transplanted Stem Cells to Mature Into Salivary Gland and Cheek Cells	NCT00023491	Graft vs Host D... Sjogren's Syndr...		-	National Institutes of Health Clinical Center (CC)
PSMA-PET Imaging of Salivary Gland Tumours and Other Rare Cancers	NCT05581979	Salivary Gland ... Rare Malignant ...	68-Ga PSMA PET ...	21 Years - 99 Years	National Cancer Centre, Singapore
A Study Evaluating the Safety and Efficacy of ENV-101 (Taladegib) in Patients With Advanced Solid Tumors Harboring PTCH1 Loss of Function Mutations	NCT05199584	Solid Tumors Wi...	ENV-101 (talade...	18 Years -	Endeavor Biomedicines, Inc.
Salivary Gland Autotransplantation for Treatment of XRT Induced Xerostomia	NCT04007081	Xerostomia Head and Neck C...	Bone Marrow Asp... Ultrasound Imag... Salivary Assay Quality of Life...	18 Years - 89 Years	University of Wisconsin, Madison
Binary Oncolytic Adenovirus in Combination With HER2-Specific Autologous CAR VST, Advanced HER2 Positive Solid Tumors	NCT03740256	Bladder Cancer Head and Neck S... Cancer of the S... Lung Cancer Breast Cancer Gastric Cancer Esophageal Canc... Colorectal Canc... Pancreatic Aden... Solid Tumor	CAdVEC	18 Years -	Baylor College of Medicine

Spots Global Cancer Trial Database for salivary gland