Microdevice for In Situ Candidate Drug Screening in Skin Lesions of T-Cell Lymphoma
- 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 cutaneous disease amenable to measurement by mSWAT. 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 (plaque or tumor lesion of a minimum diameter of 1.5 cm, and the epidermis and dermis is clinically suspected to be at least 6 mm in depth)
- Participant 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
- Participants unable to undergo treatment wash-out period due to actively progressive disease requiring immediate systemic therapy are eligible if they may safely delay initiation of next therapy to allow for microdevice implantation and retrieval (e.g. typically within 1-2 weeks) in the opinion of their treating medical or cutaneous oncology provider. Participants with stable disease on systemic therapy must undergo washout period
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Absolute neutrophil count >= 500/mcL (within 28 days prior to the procedure)
- Platelets >= 50,000/mcL (within 28 days prior to the procedure)
- 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
- Participants 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
- Participants 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 National Institute of Health (NIH) central data repositories
- Participant is considered to have capacity to properly follow instructions at home for the care of device(s) that will be glued and/or bandaged to the skin and fixed in place
- 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
- Participants 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. Consistent topical steroid use (used for >= 4 weeks prior to cycle 1 day 1 [C1D1]) may be continued to all sites except those selected to undergo implantation (must undergo washout); and following retrieval may not resume topical steroids to those sites if participant will be initiating a new systemic therapy. Should a participant clinically progress on first systemic therapy and require a change in treatment, skin directed therapies may be introduced to all skit sites
- Participants unable to undergo treatment wash-out period due to rapidly progressive disease requiring immediate systemic therapy who cannot safely delay therapy to allow for microdevice implantation and removal (e.g. typically 1-2 weeks) in the opinion of their treating medical or cutaneous oncology provider
I. To evaluate the safety of microdevice placement and removal based on assessment of adverse events.
II. To determine the feasibility of microdevice analysis based on the ability to place and retrieve the device with sufficient tissue, of sufficient quality, for downstream histopathology analysis and interpretation of at least 80% of the device reservoirs.
I. To assess specific safety and feasibility parameters of device placement.
II. To assess specific safety and feasibility parameters of device retrieval by either a) punch biopsy tool or b) standard surgical excision.
III. To measure local intralesional response to clinically relevant cancer agents in cutaneous lesions of T cell lymphomas using quantitative histopathologic assessment of tumor tissue.
IV. To perform a preliminary assessment of the correlation between the extent of tumor response to drug with the microdevice and the clinical responses to systemic therapy (via disease measurements including modified severity weighted assessment tool [mSWAT] and high-throughput T cell receptor [TCR] sequencing) and overall outcomes (including progression-free survival and overall survival).
V. To explore additional potential biomarkers of drug response, including immune infiltrates, in the local tumor tissue adjacent to the microdevice.
VI. To assess intralesional heterogeneity in drug response by comparing the extent of tumor response to drug among different locations in a single tumor with multiple microdevices.
VII. To describe the genomic aberrations of the lesion tissue where microdevice(s) will be placed (using whole exome sequencing) and the transcriptional signatures of the lesion tissue not exposed to and exposed to drug (using RNA sequencing).
VII. To perform a preliminary assessment of the correlation of genomic aberrations and perturbations in signaling pathways with extent of response to individual drugs.
Patients undergo the percutaneous placement of the microdevices and all microdevices are retrieved within 72 hours of implantation. Microdevices release drugs including interferon alpha, interferon gamma, romidepsin, olaparib, methotrexate, pralatrexate, bexarotene, brentuximab vedotin, gemcitabine, doxorubicin, pembrolizumab, ruxolitinib, venetoclax, azacytidine, duvelisib, alemtuzumab, bortezomib, palbociclib, and mogamulizumab. If surgical excision is considered by the dermatology study investigator or patient to be of such risk that is not acceptable to the patient, the microdevice(s) may be left indwelling.
After completion of study, patients are followed up every 4 weeks for 2 years.
Trial Phase Phase NA
Trial Type Diagnostic
Dana-Farber Harvard Cancer Center
Cecilia Alejandra Larocca
- Primary ID 18-639
- Secondary IDs NCI-2020-01025
- Clinicaltrials.gov ID NCT04045470