Clinical trial NCT04045470: A Pilot of a Microdevice For In Situ Candidate Drug Screening in Cutaneous Lesions of T-Cell Lymphoma
Official title: A Pilot of a Microdevice For In Situ Candidate Drug Screening in Cutaneous Lesions of T-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cutaneous T Cell Lymphoma
Peripheral T Cell Lymphoma
Keywords: Cutaneous T Cell Lymphoma
Peripheral T Cell Lymphoma
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
First posted: 2019-08-05
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Expansion cohort may enroll only after initial cohort has completed enrollment
Primary purpose: DIAGNOSTIC

Brief summary: This research is being done to study the safety of implanting and retrieving a microdevice that releases up to 19 drugs directly within a cancerous lesion as a possible tool to evaluate the effectiveness of several approved cancer drugs against cutaneous T cell lymphoma and peripheral T cell lymphoma

Detailed description: This research study is a Pilot and Feasibility Study, which is the first time investigators are examining this study microdevice loaded with drugs in patients with cutaneous lesions of cutaneous T cell lymphoma (CTCL) or peripheral T cell lymphoma (PTCL) patients.

The FDA (the U.S. Food and Drug Administration) has not approved the use of all the drugs contained in the microdevice as a treatment for cutaneous or peripheral T cell lymphoma. All drugs used in this study are FDA approved. Some drugs are for different cancer indications. Romidepsin, vorinostat, bexarotene, brentuximab vedotin, pralatrexate, and mogamulizumab have been FDA approved for CTCL. The FDA has not approved the use of the microdevice as a tool to identify what cancer treatment is best for any disease.

In this research study, the investigators are investigating whether the microdevice loaded with 19 drugs can be safely inserted in and removed from cancerous skin lesion. The microdevice was developed as a tool with the ultimate goal to help screen several existing and investigational drugs directly within a patient's tumor to identify what drugs are the most effective for treating a patient's cancer.

This microdevice was investigated in laboratory studies and shown to help identify what drugs could be effective in treating a specific cancer type. The microdevice was able to release drugs only to the immediately surrounding tumor tissue in concentrations of one millionth of what is normally needed for a therapeutic dose. The microdevice can be retrieved along with a few millimeters of surrounding treated tumor tissue for analysis of tumor response to drug.

Eligibility criteria: Inclusion Criteria:

* Participants must have clinical diagnosis of cutaneous T-cell lymphoma or peripheral T-cell lymphoma with cutaneous involvement supported by histological evaluation of skin lesions.
* Participants must have measurable cutaneous disease, based on the modified Severity Weighted Assessment Tool (mSWAT; definition provided in appendix E). Skin lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
* Two lesions are amenable to placement of multiple devices in terms of lesion size and location, as assessed by dermatologist (minimum diameter of 1.5 cm).
* Patient must have the following minimum washout period from previous treatments and cannot be on any systemic therapy at the time of implantation.

  * 2 week from topical therapies of lesional skin selected for implantation
  * 2 weeks from retinoids, interferons, vorinostat, romidepsin, therapeutic doses of oral corticosteroids (physiologic replacement doses of oral corticosteoids are allowed)
  * 4 weeks from phototherapy
  * 5 half-lives for systemic cytotoxic anticancer agents, monoclonal antibodies, and investigational therapy
  * 12 weeks from local radiation therapy of lesional skin selected for implantation
  * 15 weeks from systemic immunotherapy targeting PD-1/PD-L1
* Age minimum of age 18.
* ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
* Participants will undergo laboratory testing within 28 days prior to the procedure. Participants must have marrow function as defined below:

  * absolute neutrophil count ≥500/mcL
  * platelets ≥50,000/mcL
* Participants must be evaluated by a dermatologist or medical oncologist who will determine the clinically appropriate treatment strategy based on clinical history and extent of disease. Systemic therapy will be mandatory for cohort 2/expansion cohort, not for cohort 1. Systemic therapy may be initiated anytime within 4 weeks of MD removal.
* Patients must be deemed medically stable to undergo percutaneous procedures by their treating cutaneous oncologist.
* Ability to understand and the willingness to sign a written informed consent document.
* Patients must be willing to undergo research-related genetic and transcriptomic sequencing (somatic and germline) and data management, including the deposition of de-identified genetic sequencing data in NIH central data repositories.
* Patient is considered to have capacity to properly follow instructions at home for the care of device(s) that will each have an attached thin guidewire protruding through the skin and fixed in place (see Appendix B).

Exclusion Criteria:

* Positive serum pregnancy test at screening visit.
* Uncorrectable bleeding or coagulation disorder known to cause increased risk with surgical or biopsy procedures
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in this study.
* 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 compliance with study requirements.
* Patients who will receive standard of care systemic therapy are not allowed to start any new skin directed therapy (e.g. topical steroids, radiation, phototherapy) concurrent with first systemic therapy initiated after device implantation and retrieval. Should a patient clinically progress on first systemic therapy and require a change in treatment, skin directed therapies may be introduced.
* Patients unable to undergo treatment wash-out period due to rapidly progressive disease requiring immediate systemic therapy

Primary outcomes:
measure: To Quantify The Number Of Microdevice-Related Failures Or Adverse Events As Assessed By CTCAE v4.0 After Microdevice Placement and Removal
timeFrame: 2 years
measure: To Retrieve The Device With Sufficient Tissue Of Sufficient Quality
timeFrame: 2 years
Secondary outcomes:
measure: Local Intralesional Response To Clinically Relevant Cancer Agents In Cutaneous T Cell Lymphomas
timeFrame: 2 years
measure: Intralesional Heterogeneity In Drug Response Using Quantitative Histopathologic Assessment Of Tumor Tissue
timeFrame: 2 years
measure: Assessment Of Microdevice-Predicted Tumor Response To Drug
timeFrame: 3 years
measure: Quantitative Assessment Of Drug Effect On The Tumor Microenvironment And Signal Pathways By Immunofluorescence
timeFrame: 5 years
measure: To Identify Genomic And Transcriptomic Biomarkers of Drug Response by Whole Exome and RNA Sequencing and Subsequent Correlations To Microdevice Predicted Tumor Response
timeFrame: 5 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Cecilia Larocca, MD
role: PRINCIPAL_INVESTIGATOR
References: