Drug Screening Using Novel IMD in ACC and Salivary Cancers

Study Overview
=================
Brief Summary
-----------------
This research study is studying the effect of different drugs as possible treatments for adenoid cystic carcinoma (ACC), a type of head and neck cancer. The name of the study intervention involved in this study is: -implantable microdevice

Detailed Description
-----------------
This window-of-opportunity pilot study will assess the safety and feasibility of using an implantable microdevice (IMD) to efficiently measure local intratumor response to multiple drugs within previously untreated salivary gland ACC patients undergoing definitive oncologic resection. -This research study is a Pilot Study, which is the first-time investigators are examining this study device in ACC. The treatment received (surgery and/or chemotherapy) will be the normal standard-of-care treatment for ACC. However, the placement and removal of the microdevice is being tested for the first time in this type of cancer. This research study involves drugs that are released by a small implantable microdevice (IMD) as small as the tip of a needle, that is inserted into the tumor and is then removed 3-5 days later during surgery. The microdevice can hold up to 20 drugs in very small concentrations that are able to access the cancer through small pores in the device. When the device is removed along with the cancer at the time of surgery, it will be evaluated to understand which drug(s) may be effective to treat these cancers. It is expected that about 30 people will take part in this research study. The U.S. Food and Drug Administration (FDA) has not approved the microdevice a treatment for any disease. AACRF, a research foundation, is supporting this research study by providing funding for the research study, the study drugs and study procedures.

Official Title
-----------------
Therapeutic Drug Screening Using a Novel Implantable Microdevice (IMD) in Adenoid Cystic Carcinoma (ACC) and Salivary Cancers: a Window of Opportunity Study

Conditions
-----------------
Adenoid Cystic Carcinoma, Adenoid Cystic Carcinoma of the Salivary Gland

Intervention / Treatment
-----------------
* Combination Product: Implantable Microdevice (IMD)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must have histologically confirmed adenoid cystic carcinoma (ACC) of the salivary glands of the head and neck without evidence of recurrent, metastatic or advanced, incurable disease undergoing definitive surgical management; any stage disease is permitted (American Joint Committee on Cancer 2017 8th edition). If initial fine needle aspiration (FNA) biopsy shows findings suggestive of ACC or a basaloid neoplasm, the patient is considered eligible. Initial FNAs showing unspecified salivary neoplasms should be discussed with the treating surgeon and PI. Age 18 years or older. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. A measurable primary tumor site both clinically and radiologically measuring at least 1 x 1 cm. Patients must be deemed medically fit to undergo both percutaneous and surgical procedures by their treating head and neck surgeon and medical oncologist. Participants will undergo laboratory testing within 7 days prior to the microdevice placement: they are required to have a platelet count ≥50,000/mcL, PT/INR <2, and aPTT <1.5x upper limit of normal. Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 14 days Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Participants who are receiving any other investigational agents. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit the safety of a biopsy and/or surgery. Pregnant women are excluded from this study because of the possible increased dose of radiation from imaging associated with the device placement and the potential risk to the pregnancy of the surgery/device placement. Uncorrectable bleeding or coagulation disorder known to cause increased risk with surgical or percutaneous biopsy procedures. If the patient is on systemic anticoagulation, this should be discussed with the overall PI and treating surgeon

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMD PLACEMENT + SURGICAL RESECTION + ADJUVANT TREATMENT ARM<br>Newly diagnosed, localized ACC salivary cancers undergoing surgical resection Interventional radiology guided IMD placement Planned oncologic resection with IMD retrieval 3-5 days after placement Standard of care adjuvant treatment Tumor specimen analysis for local drug response and molecular analysis | Combination Product: Implantable Microdevice (IMD)<br>* Percutaneous CT image-guided placement of the microdevice(s). At least one, and up to 3, devices will be placed in each tumor. Drugs will be released from the microdevice into local tumor tissues. The duration of drug release will be for a period of 3-5 days while the microdevice is in the tumor prior to retrieval. The local tissue is retrieved along with the microdevice and no residual drug will remain. Each microdevice harbors up to 20 drugs and/or drug combinations relevant to the treatment of salivary cancer. The drugs used will include some standard agents approved by the Food and Drug Administration (FDA) for treatment of different types of cancers, or drugs classes under investigational. Drugs may include all or a subset of the following which each may be tested as single agents or in any number of combinations: Lenvatinib, Axitinib, All trans retinoic acid (ATRA), Venetoclax, Pembrolizumab, Cisplatin, Carboplatin, Vinorelbine<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 3 or Higher Treatment-Related Toxicity Rate | All grade 3 or higher adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms were counted. Rate is the proportion of treated participants experiencing at least one treatment-related grade 3 or higher AE of any type during the time of observation. | AE assessed on post-operative visit, which take placed between 7-14 days after the surgical procedure. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamic (PD) | Pharmacodynamics reported based on dose/exposure efficacy and safety relationships, there are no clinically significant differences in efficacy and safety between pembrolizumab doses of 200 mg or 2 mg/kg every 3 weeks in patients with melanoma or NSCLC. | Screening Period 1 day | 
| Evaluate the likelihood of independent drug or combination response/failure in this pilot population to determine the appropriateness of nominating therapies for further clinical investigation |  | through study completion, an average of 1 year | 
| Tumor Response | Tumor molecular profiling using a commercially available assay (CARIS® MI Profile) will be performed on pathology material from resection sent for permanent processing using cut unstained tissue slides, in post-operative visit up 14 days | through study completion, an average of 1 year | 
| Gene Expression Level | Tumor molecular profiling using a commercially available assay (CARIS® MI Profile) will be performed on pathology material from resection sent for permanent processing using cut unstained tissue slides, in post-operative visit up to 14 Days | through study completion, an average of 1 year | 
| Changes in Tumor Metabolism | Tumor molecular profiling using a commercially available assay (CARIS® MI Profile) will be performed on pathology material from resection sent for permanent processing using cut unstained tissue slides, in post-operative visit up to 14 Days | through study completion, an average of 1 year | 
| Biomarker levels | For hypothesis-generating biomarker discovery, genome-wide approaches looking at both established and novel candidate biomarkers may be able to identify new biomarkers exclusive to ACC | through study completion, an average of 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Adenoid Cystic Carcinoma, Adenoid Cystic Carcinoma of the Salivary Gland, Implantable Microdevice IMD