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Pilot Study of an Implantable Microdevice for Evaluating Drug Responses in Situ in Prostate Cancer

Primary Purpose

Prostate Cancer, Radical Prostatectomy

Status

Enrolling by invitation

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Microdevice

About this trial

This is an interventional diagnostic trial for Prostate Cancer focused on measuring Prostate Cancer, Radical Prostatectomy

Eligibility Criteria

22 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Eligibility Criteria Ex Vivo Cohort
- Participants must have the ability to understand and the willingness to sign a written informed consent document.
- Planned Radical Prostatectomy for Prostate Cancer.
- Participants must be 22 years of age or older.
Eligibility Criteria for Surgical Cohort
- Participants must have the ability to understand and the willingness to sign a written informed consent document.
- Participants must present with prostate cancer falling into an intermediate or high risk category to include features: Gleason score 3+4 or higher, greater than 3 biopsy cores positive and >50% of 1 core positive for carcinoma, and an MRI-visible lesion concerning for PCa in the region of the positive biopsy.
- Participants must be 22 years of age or older.
- Participants must be evaluated by a urologic oncologist who will determine the clinically appropriate treatment strategy based on clinical history and extent of disease.
- Participants must be deemed medically stable to undergo both percutaneous procedures and standard-of-care surgical procedures by their treating surgeon.
- Participants will undergo laboratory testing within 30 days prior to the procedure (or within 72 hours if there has been a change in the clinical status since the initial blood draw). Participants must have absolute neutrophil count ≥1,500/mcL, platelets ≥50,000/mcL, PT (INR) 0.8-1.2 and PTT within the normal range of the institution.
- Participants must have undergone multi-parametric prostate MRI that both assesses the extent of disease and allows the research team to assess for study eligibility. This will have been done as part of the standard-of-care. Abnormal imaging will be correlated with the biopsy findings to maximize the likelihood of the device being put in the lesion. If the images are not adequate, the MRI scan will be repeated at BWH/DFCI, again as part of standard-of-care management.
- The participant's case must be reviewed by representatives of urologic oncology and interventional radiology to assess the following factors:
  - Participant is clinically stable to undergo biopsy procedure(s) and surgical procedures
  - Participant has sufficient volume of disease as shown by MRI to allow implantation of the microdevice
  - A lesion can be selected where the microdevice is to be implanted that is a) amenable to percutaneous placement, and b) amenable to removal at the time of primary surgery -- Participants must be willing to undergo research-related genetic sequencing (somatic and germline) and data management, including the deposition of de-identified genetic sequencing data in NIH central data repositories.
Exclusion Criteria:
- 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.
- Uncorrectable bleeding or coagulation disorder known to cause increased risk with surgical or biopsy procedures (detailed below).

Sites / Locations

Brigham and Women's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Surgery Cohort

Ex-Vivo Cohort

Arm Description

Participant eligibility for intervention and selection of lesion for device placement - Surgery Cohort will undergo percutaneous placement of several microdevices in a selected tumor(s) prior to surgery. The microdevice in the surgery cohort will dwell in the tumor tissue for approximately 48 hours to allow time for tissue effects of the drugs in the microdevice reservoirs. Placement of at least 1, and up to 6, microdevices depending on the number of lesions, size and accessibility Extirpative surgery will proceed according to standard-of-care procedures. The microdevice(s) will be removed surgically along with surrounding tumor tissue. Standard of care treatment and follow-up of clinical course

Each participant will undergo a screening process to determine their eligibility for microdevice placement, consisting of the following items: Routine standard of care for radical prostatectomy. Placement of implantable microdevice with multiple miniature drug reservoirs but no drug in prostate that have been removed Ex vivo image guided removal using retrieval device Standard of Care Treatment and follow-up of clinical course

Outcomes

Primary Outcome Measures

Number of participants with adverse events as defined in the CTCAE v4.0

Safety of microdevice placement and removal based on assessment of adverse events

Number of Participants with successful surgical Placement and retrieval of Microdevice

Feasibility of microdevice placement based on the ability in the Surgical Cohort to percutaneously place and surgically retrieve the device with sufficient tissue, of sufficient quality, for downstream histopathology analysis and interpretation. In the Surgical Cohort, if not more than 1 IMD per patient fails to be percutaneously placed and surgically retrieved with sufficient tissue of sufficient quality for downstream histopathology analysis and interpretation, we would consider this procedure to be a success. If at least 23/30 Surgical Cohort patients have successful procedures, as previously defined, we would consider this approach feasible. The 90% CI for 23 out of 30 successes is (60.6%, 88.5%) and thus excluding a 60% success rate which is considered as too low.

Secondary Outcome Measures

Local intratumor response

measure local intratumor response to clinically relevant cytotoxic agents and small molecule drugs in prostate cancers using quantitative histopathologic assessment of tumor tissue. All inferences of secondary endpoints will use two-sided alpha = 0.05 and report 95% confidence intervals with any point estimates. Descriptive statistics will be used to summarize the quantitative measurements of apoptosis, proliferation, DNA repair, etc. for drug-treated regions compared to vehicle-treated regions. At least two separate regions will contain vehicle to account for tumor heterogeneity.

Intratumor heterogeneity in drug response

comparing the extent of tumor response to drug among different locations in a single tumor with multiple microdevice. All inferences of secondary endpoints will use two-sided alpha = 0.05 and report 95% confidence intervals with any point estimates.

Biomarkers of drug response

immune infiltrates, in the local tumor tissue adjacent to the microdevice, and to perform a preliminary assessment of the correlation between these features and extent of tumor response with the microdevice All inferences of secondary endpoints will use two-sided alpha = 0.05 and report 95% confidence intervals with any point estimates.

Genetic features of the tumor tissue

To determine the genetic features of the tumor tissue adjacent to the microdevice (e.g. whole exome sequencing, whole transcriptome sequencing) and to perform a preliminary assessment of the correlation between known genetic markers of drug sensitivity or resistance and extent of tumor response with the microdevice Genetic alterations will be catalogued in terms of single nucleotide variants, insertions/deletions, and copy number changes and will be primarily reported in a descriptive manner. Preliminary correlations between a specific genetic feature and specific clinical features will be tested using the Chi-squared/Fisher's exact test for categorical variables or the T-test or Wilcoxon Rank-Sum test for continuous variables

Full Information

NCT ID

NCT04399876

First Posted

May 19, 2020

Last Updated

August 16, 2022

Sponsor

Dana-Farber Cancer Institute

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT04399876

Brief Title

Pilot Study of an Implantable Microdevice for Evaluating Drug Responses in Situ in Prostate Cancer

Official Title

Pilot Study of an Implantable Microdevice for Evaluating Drug Responses in Situ in Prostate

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Enrolling by invitation

Study Start Date

June 22, 2020 (Actual)

Primary Completion Date

March 1, 2025 (Anticipated)

Study Completion Date

March 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Dana-Farber Cancer Institute

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

In this research study, is assessing the feasibility of using an MR-guided implantable microdevice to measure tumor response to chemotherapy and other clinically relevant drugs in participants that have prostate cancer and are scheduled for a radical prostatectomy. The name of the study intervention involved in this study is: - Implantation of a MR-guided microdevice

Detailed Description

This research study is assessing the feasibility and safety of implanting and retrieving a 'microdevice' that releases up to 20 drugs directly within the prostate cancer lesion as a possible tool to evaluate the effectiveness of several approved cancer drugs against prostate cancer. Participants will be identified with confirmed prostate cancer whose treatment plan includes surgery as a component of standard-of-care treatment. The name of the study intervention involved in this study is: Implantation of a MR-guided microdevice . It is expected that about 35 people will take part in this research study; 5 in the Ex Vivo Cohort and 30 in Surgery Cohort. Ex Vivo Cohort will undergo placement of microdevice in the prostate after its surgical removal. Surgery Cohort will undergo percutaneous placement of several microdevices in a selected tumor prior to surgery. This research study is a Pilot Study, which is the first-time investigators are examining this study intervention. The FDA (the U.S. Food and Drug Administration) has not approved the implantation of the microdevice for this specific disease, but usage of this has been approved for other uses.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer, Radical Prostatectomy

Keywords

Prostate Cancer, Radical Prostatectomy

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Surgery Cohort

Arm Type

Experimental

Arm Description

Arm Title

Ex-Vivo Cohort

Arm Type

Experimental

Arm Description

Intervention Type

Combination Product

Intervention Name(s)

Microdevice

Intervention Description

Surgery Cohort: Placement of 1-6 microdevices: Drugs chosen have all been FDA approved for the treatment of cancer (so therefore safe) and there are phase 2 or 3 data that the drug has efficacy in prostate cancer. Agents of interest included Abiraterone, Enzalutamide, Pembrolizumab, Ipilimumab, Carboplatin, Docetaxel, and Olaparib as well as combinations Ex vivo Cohort: Placement of multiple microdevices with miniature drug reservoirs but no drug is loaded into the removed prostate

Primary Outcome Measure Information:

Title

Number of participants with adverse events as defined in the CTCAE v4.0

Description

Safety of microdevice placement and removal based on assessment of adverse events

Time Frame

From the time of arrival to interventional radiology for microdevice placement up to 6 weeks.

Title

Number of Participants with successful surgical Placement and retrieval of Microdevice

Description

Time Frame

48 Hours

Secondary Outcome Measure Information:

Title

Local intratumor response

Description

Time Frame

48 Hours

Title

Intratumor heterogeneity in drug response

Description

Time Frame

48 Hours

Title

Biomarkers of drug response

Description

Time Frame

48 Hours

Title

Genetic features of the tumor tissue

Description

Time Frame

48 Hours

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

22 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Eligibility Criteria Ex Vivo Cohort Participants must have the ability to understand and the willingness to sign a written informed consent document. Planned Radical Prostatectomy for Prostate Cancer. Participants must be 22 years of age or older. Eligibility Criteria for Surgical Cohort Participants must have the ability to understand and the willingness to sign a written informed consent document. Participants must present with prostate cancer falling into an intermediate or high risk category to include features: Gleason score 3+4 or higher, greater than 3 biopsy cores positive and >50% of 1 core positive for carcinoma, and an MRI-visible lesion concerning for PCa in the region of the positive biopsy. Participants must be 22 years of age or older. Participants must be evaluated by a urologic oncologist who will determine the clinically appropriate treatment strategy based on clinical history and extent of disease. Participants must be deemed medically stable to undergo both percutaneous procedures and standard-of-care surgical procedures by their treating surgeon. Participants will undergo laboratory testing within 30 days prior to the procedure (or within 72 hours if there has been a change in the clinical status since the initial blood draw). Participants must have absolute neutrophil count ≥1,500/mcL, platelets ≥50,000/mcL, PT (INR) 0.8-1.2 and PTT within the normal range of the institution. Participants must have undergone multi-parametric prostate MRI that both assesses the extent of disease and allows the research team to assess for study eligibility. This will have been done as part of the standard-of-care. Abnormal imaging will be correlated with the biopsy findings to maximize the likelihood of the device being put in the lesion. If the images are not adequate, the MRI scan will be repeated at BWH/DFCI, again as part of standard-of-care management. The participant's case must be reviewed by representatives of urologic oncology and interventional radiology to assess the following factors: Participant is clinically stable to undergo biopsy procedure(s) and surgical procedures Participant has sufficient volume of disease as shown by MRI to allow implantation of the microdevice A lesion can be selected where the microdevice is to be implanted that is a) amenable to percutaneous placement, and b) amenable to removal at the time of primary surgery -- Participants must be willing to undergo research-related genetic sequencing (somatic and germline) and data management, including the deposition of de-identified genetic sequencing data in NIH central data repositories. Exclusion Criteria: 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. Uncorrectable bleeding or coagulation disorder known to cause increased risk with surgical or biopsy procedures (detailed below).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Adam S Kibel, MD

Organizational Affiliation

Brigham and Women's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Brigham and Women's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

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 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

Contact the Partners Innovations team at http://www.partners.org/innovation

Learn more about this trial

Pilot Study of an Implantable Microdevice for Evaluating Drug Responses in Situ in Prostate Cancer

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