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A Pilot of a Microdevice For In Situ Candidate Drug Screening in Cutaneous Lesions of T-Cell Lymphoma

Primary Purpose

Cutaneous T Cell Lymphoma, Peripheral T Cell Lymphoma

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Microdevices
Standard of care therapy
Standard of care systemic therapy
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Cutaneous T Cell Lymphoma focused on measuring Cutaneous T Cell Lymphoma, Peripheral T Cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Dana Farber Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Initial Cohort

Expansion Cohort

Arm Description

Patients with plaque or tumor skin lesions of cutaneous T cell lymphoma or peripheral T cell lymphoma Mandatory skin biopsy for corollary studies will be obtained Patients will undergo percutaneous placement of four total microdevice(s) into two skin lesions (2 MD per skin lesion)

Only patients with plaque or tumor skin lesions of cutaneous T cell lymphoma or peripheral T cell lymphoma who plan to start systemic therapy as part of standard of care Mandatory skin biopsy for corollary studies will be obtained Patients will undergo percutaneous placement of four total microdevice(s) into two skin lesions (2 MD per skin lesion) Participants will receive standard of care therapy and clinical course followed Participants will undergo standard of care therapy as previously determined by treating oncologist and/or dermatologist prior to enrollment to study Participants will not be assigned any treatment intervention

Outcomes

Primary Outcome Measures

To Quantify The Number Of Microdevice-Related Failures Or Adverse Events As Assessed By CTCAE v4.0 After Microdevice Placement and Removal
"Failure" will be considered any of the following: Any grade 3 or 4 adverse events associated with device placement or retrieval Any device resulting in "major" adverse events as listed below: device unable to be found or unable to be retrieved device invading into vessel or device embolism infection or severe tissue damage or abnormal wound healing associated with device or procedure (as deemed by a neutral consultant e.g. dermatologist, ID specialist or surgeon) severe allergic/hypersensitivity reaction severe bleeding Any device resulting in *two or more* "minor" adverse events as listed below: device migration more than 10 mm device fracture not causing a major adverse event mild allergic/hypersensitivity reaction manageable pain associated with biopsy procedure minor bleeding For purposes of this endpoint, safety will be evaluated on a per-patient level, where an event is defined as any "failure" observed among all implanted devices.
To Retrieve The Device With Sufficient Tissue Of Sufficient Quality
For the feasibility endpoint, a "successful" procedure will be defined as the ability to retrieve the device (by either skin punch biopsy tool or surgical excision) without damaging tumor tissue surrounding the microdevice to allow for immunohistochemistry analysis. For purposes of this endpoint, feasibility will be assessed on a per-device basis rather than a per-patient basis, with each device considered relatively independent in terms of placement, retrieval, and analysis.

Secondary Outcome Measures

Local Intralesional Response To Clinically Relevant Cancer Agents In Cutaneous T Cell Lymphomas
Intralesional Heterogeneity In Drug Response Using Quantitative Histopathologic Assessment Of Tumor Tissue
Comparison of tumor responses to like drug delivered from separate microdevices.
Assessment Of Microdevice-Predicted Tumor Response To Drug
Correlation of tumor response to drug released by microdevice compared with clinical response to systemic administration of like drug
Quantitative Assessment Of Drug Effect On The Tumor Microenvironment And Signal Pathways By Immunofluorescence
Descriptive statistics will be used to summarize the quantitative measurements in cell number of different immunophenotypes and quantify signal transduction cascades. Descriptive statistics will be employed to summarize the variance in different measures of drug-induced microenvironment changes across participants.
To Identify Genomic And Transcriptomic Biomarkers of Drug Response by Whole Exome and RNA Sequencing and Subsequent Correlations To Microdevice Predicted Tumor Response
Genetic alterations will be cataloged in terms of single nucleotide variants, insertions/deletions, and copy number changes and will be reported in a descriptive manner. Preliminary correlations between a specific genetic feature and specific clinical features will be tested using Fisher's exact test for categorical variables or the Wilcoxon Rank-Sum test for continuous variables. Analyses of correlations between genetic and clinical features in different specimen types and patient groups are exploratory, and will rely on descriptive statistics without formal hypothesis testing. For each genetic feature of interest (e.g. mutation, gene expression profile) we will divide patient samples into groups based on the presence or absence of the feature. We will then assess whether the presence of the feature is associated with clinical outcomes using odds ratios, or correlation between genetic feature and overall survival, using Kaplan Meier estimates, with 95% confidence intervals to each.

Full Information

First Posted
July 25, 2019
Last Updated
August 25, 2023
Sponsor
Dana-Farber Cancer Institute
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1. Study Identification

Unique Protocol Identification Number
NCT04045470
Brief Title
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 11, 2019 (Actual)
Primary Completion Date
January 1, 2025 (Anticipated)
Study Completion Date
January 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cutaneous T Cell Lymphoma, Peripheral T Cell Lymphoma
Keywords
Cutaneous T Cell Lymphoma, Peripheral T Cell Lymphoma

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Model Description
Expansion cohort may enroll only after initial cohort has completed enrollment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Initial Cohort
Arm Type
Experimental
Arm Description
Patients with plaque or tumor skin lesions of cutaneous T cell lymphoma or peripheral T cell lymphoma Mandatory skin biopsy for corollary studies will be obtained Patients will undergo percutaneous placement of four total microdevice(s) into two skin lesions (2 MD per skin lesion)
Arm Title
Expansion Cohort
Arm Type
Experimental
Arm Description
Only patients with plaque or tumor skin lesions of cutaneous T cell lymphoma or peripheral T cell lymphoma who plan to start systemic therapy as part of standard of care Mandatory skin biopsy for corollary studies will be obtained Patients will undergo percutaneous placement of four total microdevice(s) into two skin lesions (2 MD per skin lesion) Participants will receive standard of care therapy and clinical course followed Participants will undergo standard of care therapy as previously determined by treating oncologist and/or dermatologist prior to enrollment to study Participants will not be assigned any treatment intervention
Intervention Type
Device
Intervention Name(s)
Microdevices
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Standard of care therapy
Intervention Description
Participant to receive standard of care therapy as previously determined by participant's treating oncologist and/or dermatologist, which may include a skin-directed or systemic therapy
Intervention Type
Other
Intervention Name(s)
Standard of care systemic therapy
Intervention Description
Participant to receive standard of care therapy as previously determined by participant's treating oncologist and/or dermatologist, which must include a systemic therapy.
Primary Outcome Measure Information:
Title
To Quantify The Number Of Microdevice-Related Failures Or Adverse Events As Assessed By CTCAE v4.0 After Microdevice Placement and Removal
Description
"Failure" will be considered any of the following: Any grade 3 or 4 adverse events associated with device placement or retrieval Any device resulting in "major" adverse events as listed below: device unable to be found or unable to be retrieved device invading into vessel or device embolism infection or severe tissue damage or abnormal wound healing associated with device or procedure (as deemed by a neutral consultant e.g. dermatologist, ID specialist or surgeon) severe allergic/hypersensitivity reaction severe bleeding Any device resulting in *two or more* "minor" adverse events as listed below: device migration more than 10 mm device fracture not causing a major adverse event mild allergic/hypersensitivity reaction manageable pain associated with biopsy procedure minor bleeding For purposes of this endpoint, safety will be evaluated on a per-patient level, where an event is defined as any "failure" observed among all implanted devices.
Time Frame
2 years
Title
To Retrieve The Device With Sufficient Tissue Of Sufficient Quality
Description
For the feasibility endpoint, a "successful" procedure will be defined as the ability to retrieve the device (by either skin punch biopsy tool or surgical excision) without damaging tumor tissue surrounding the microdevice to allow for immunohistochemistry analysis. For purposes of this endpoint, feasibility will be assessed on a per-device basis rather than a per-patient basis, with each device considered relatively independent in terms of placement, retrieval, and analysis.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Local Intralesional Response To Clinically Relevant Cancer Agents In Cutaneous T Cell Lymphomas
Time Frame
2 years
Title
Intralesional Heterogeneity In Drug Response Using Quantitative Histopathologic Assessment Of Tumor Tissue
Description
Comparison of tumor responses to like drug delivered from separate microdevices.
Time Frame
2 years
Title
Assessment Of Microdevice-Predicted Tumor Response To Drug
Description
Correlation of tumor response to drug released by microdevice compared with clinical response to systemic administration of like drug
Time Frame
3 years
Title
Quantitative Assessment Of Drug Effect On The Tumor Microenvironment And Signal Pathways By Immunofluorescence
Description
Descriptive statistics will be used to summarize the quantitative measurements in cell number of different immunophenotypes and quantify signal transduction cascades. Descriptive statistics will be employed to summarize the variance in different measures of drug-induced microenvironment changes across participants.
Time Frame
5 years
Title
To Identify Genomic And Transcriptomic Biomarkers of Drug Response by Whole Exome and RNA Sequencing and Subsequent Correlations To Microdevice Predicted Tumor Response
Description
Genetic alterations will be cataloged in terms of single nucleotide variants, insertions/deletions, and copy number changes and will be reported in a descriptive manner. Preliminary correlations between a specific genetic feature and specific clinical features will be tested using Fisher's exact test for categorical variables or the Wilcoxon Rank-Sum test for continuous variables. Analyses of correlations between genetic and clinical features in different specimen types and patient groups are exploratory, and will rely on descriptive statistics without formal hypothesis testing. For each genetic feature of interest (e.g. mutation, gene expression profile) we will divide patient samples into groups based on the presence or absence of the feature. We will then assess whether the presence of the feature is associated with clinical outcomes using odds ratios, or correlation between genetic feature and overall survival, using Kaplan Meier estimates, with 95% confidence intervals to each.
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cecilia Larocca, MD
Phone
617-632-6571
Email
clarocca@partners.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cecilia Larocca, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cecilia Larocca, MD
Phone
617-632-6571
Email
clarocca@partners.org
First Name & Middle Initial & Last Name & Degree
Cecilia Larocca, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
IPD Sharing Time Frame
Data can be shared no earlier than 1 year following the date of publication
IPD Sharing Access Criteria
BCH - Contact the Technology & Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

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A Pilot of a Microdevice For In Situ Candidate Drug Screening in Cutaneous Lesions of T-Cell Lymphoma

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