search
Back to results

Non-fucosylated Anti-CTLA-4 (BMS-986218) + Degarelix Acetate vs. Degarelix Acetate Alone in Men With High-risk Localized Prostate Cancer (Neo-Red-P)

Primary Purpose

Prostate Cancer

Status
Active
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
BMS-986218 and Degarelix
Degarelix
Sponsored by
Columbia University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

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

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate (clinical stage T1c-T3b, N0, M0) without involvement of lymph nodes, bone, or visceral organs
  • Initial prostate biopsy is available for central pathologic review, and is confirmed to show at least 2 positive cores and a Gleason sum of ≥4+3
  • Radical prostatectomy has been scheduled at Columbia University Irving Medical Center
  • Age ≥18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1, or Karnofsky score ≥ 70% (see Appendix A)
  • Adequate bone marrow, hepatic, and renal function:

    • White blood cell count (WBC) >3,000 cells/mm3
    • Absolute neutrophil count (ANC)>1,500 cells/mm3
    • Hemoglobin >9.0 g/dL
    • Platelet count >100,000 cells/mm3
    • Serum creatinine <1.5 × upper limit of normal (ULN)
    • Serum bilirubin <1.5 × ULN
    • Alanine transaminase (ALT) <3 × ULN
    • Aspartate aminotransferase (AST)<3 × ULN
    • Alkaline phosphatase <3 × ULN
  • Willingness to provide written informed consent and HIPAA authorization for the release of personal health information, and the ability to comply with the study requirements (note: HIPAA authorization will be included in the informed consent)
  • Willingness to use barrier contraception from the time of first dose of BMS-986218 until 165 days from the last dose of BMS-986218.

Exclusion Criteria:

  • Presence of known lymph node involvement or distant metastases
  • Other histologic types of prostate cancers such as ductal, sarcomatous, lymphoma, small cell, and neuroendocrine tumors
  • Prior radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for prostate cancer
  • Prior immunotherapy/vaccine therapy for prostate cancer
  • Concomitant treatment with other hormonal therapy or 5α-reductase inhibitors (prior use of these agents is allowed).
  • Conditions requiring systemic treatment with either corticosteroids > 10 mg daily prednisone equivalents or other immunosuppressive medications within 14 days of study treatment administration, except for adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease.

    (1) Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating study treatment is permitted.

  • History of known or suspected autoimmune disease with the following exceptions:

    • Vitiligo
    • Resolved childhood atopic dermatitis
    • Psoriasis (with exception of psoriatic arthritis) not requiring systemic treatment (within the past 2 years).
    • Patients with Grave's disease or Hashimoto's thyroiditis that are now euthyroid clinically and by laboratory testing.
  • History of malignancy within the last 2 years, with the exception of non-melanoma skin cancers and superficial bladder cancer
  • Known uncontrolled or significant cardiovascular disease including, but not limited, to any of the following:

    1. Myocardial infarction or stroke/transient ischemic attack within the past 6 months.
    2. Uncontrolled angina within the past 3 months.
    3. Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes).
    4. History of other clinically significant heart disease (eg, cardiomyopathy, congestive heart failure with New York Heart Association functional classification III to IV, pericarditis, or significant pericardial effusion).
    5. History of myocarditis, regardless of etiology.
    6. Cardiovascular disease-related requirement for daily supplemental oxygen therapy.
  • Known prior or current history of HIV.
  • Patients with known untreated hepatitis B/C or those with a detectable viral load.
  • Active infection ≤7 days prior to start of treatment.
  • Live vaccine within 30 days of start of treatment.
  • Prior history of hypersensitivity to a monoclonal antibody.

Sites / Locations

  • Columbia University Irving Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Active Comparator

Experimental

Arm Label

Safety lead-in

Arm A

Arm B

Arm Description

The first 4 subjects enrolled will be given degarelix plus BMS-986218.

Degarelix 240mg subcutaneous (SQ) x1 dose 2 weeks prior to radical prostatectomy

BMS-986218 20mg IV every 2 weeks x 2 doses starting 3 weeks prior to radical prostatectomy plus degarelix 240mg SQ x1 dose 2 weeks prior to radical prostatectomy.

Outcomes

Primary Outcome Measures

The proportion of patients with an adverse event will be reported with an exact binomial 95% confidence interval
Characterizing the safety, tolerability, and feasibility of degarelix with or without BMS-986218 in the neoadjuvant setting. All subjects receiving at least one dose of the study drug(s) will be evaluable for toxicity.

Secondary Outcome Measures

Mean Treg cell staining percentage in harvested prostate tissues will be reported and compared post-treatment between the treatment groups using paired sample test.
The standard deviation, 95% confidence interval, median, and range of values will also be reported where appropriate
Pathological complete responses (pCR)- an absence of tumor identification on standard histological analysis of the resected prostate specimens.
The estimate and 95% confidence intervals will be obtained.
Undetectable PSA at 12 months- the proportion of patients who achieve an undetectable PSA (<0.1 ng/mL) by 12 months after prostatectomy
The estimate and 95% confidence intervals will be obtained.
PSA response rates- a 50% change in pre-treatment and post-treatment PSA.
These endpoints will be expressed as the proportion of men achieving a PSA response. The estimate and 95% confidence intervals will be obtained.
Time to PSA recurrence- the interval from the time of prostatectomy to the time when the first of at least two serial rises in PSA (≥2 weeks apart) with a PSA ≥0.2 ng/mL.
PSA will be measured every 3 (±1) months during the first post-operative year and every 6 (±2) months during the second and third post-operative years. For subjects who have not yet demonstrated PSA relapse after 3 years followup patients will be censored at the date of the last assessment that shows a lack of PSA recurrence. This outcome will be expressed as a median (95% CI) and will be determined using the Kaplan-Meier method.

Full Information

First Posted
March 6, 2020
Last Updated
March 22, 2023
Sponsor
Columbia University
Collaborators
Bristol-Myers Squibb, Ferring Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT04301414
Brief Title
Non-fucosylated Anti-CTLA-4 (BMS-986218) + Degarelix Acetate vs. Degarelix Acetate Alone in Men With High-risk Localized Prostate Cancer
Acronym
Neo-Red-P
Official Title
A Pilot Study of Neoadjuvant Non-fucosylated Anti-CTLA-4 (BMS-986218) + Degarelix Acetate vs. Degarelix Acetate Alone in Men With High-risk Localized Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 25, 2020 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
June 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Columbia University
Collaborators
Bristol-Myers Squibb, Ferring Pharmaceuticals

4. Oversight

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

5. Study Description

Brief Summary
The purpose of this study is to see whether immunotherapy with BMS-986218 added to degarelix (which suppresses testosterone) given prior to surgery can decrease the chance that cancer will come back compared to degarelix alone. People who usually have this type of prostate cancer usually do not receive any additional therapy prior to surgery. Approximately 24 individuals will be asked to participate in this study.
Detailed Description
This is a single-center, randomized, two-arm, study evaluating the safety, feasibility and immunogenicity of neoadjuvant degarelix(Arm A) or BMS-986218 plus degarelix (Arm B) prior to radical prostatectomy in men with high-risk localized prostate cancer (neo-RED-P). Our primary objective is to characterize safety, tolerability, and feasibility of degarelix with or without BMS-986218 in the neoadjuvant setting. The trial will monitor toxicity and safety, as well as surgery related adverse events. The secondary objectives will be to evaluate an immune response consistent with the proposed mechanism of action of BMS-986218, depletion of Tregs, and to assess the pathologic complete response rate, PSA response rate and time-to-PSA recurrence following treatment.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Safety lead-in
Arm Type
Other
Arm Description
The first 4 subjects enrolled will be given degarelix plus BMS-986218.
Arm Title
Arm A
Arm Type
Active Comparator
Arm Description
Degarelix 240mg subcutaneous (SQ) x1 dose 2 weeks prior to radical prostatectomy
Arm Title
Arm B
Arm Type
Experimental
Arm Description
BMS-986218 20mg IV every 2 weeks x 2 doses starting 3 weeks prior to radical prostatectomy plus degarelix 240mg SQ x1 dose 2 weeks prior to radical prostatectomy.
Intervention Type
Drug
Intervention Name(s)
BMS-986218 and Degarelix
Intervention Description
BMS-986218 20mg IV every 2 weeks x 2 doses starting 3 weeks prior to radical prostatectomy plus degarelix 240mg subcutaneous (SQ) x1 dose 2 weeks prior to radical prostatectomy.
Intervention Type
Drug
Intervention Name(s)
Degarelix
Intervention Description
Degarelix 240mg SQ x1 dose 2 weeks prior to radical prostatectomy
Primary Outcome Measure Information:
Title
The proportion of patients with an adverse event will be reported with an exact binomial 95% confidence interval
Description
Characterizing the safety, tolerability, and feasibility of degarelix with or without BMS-986218 in the neoadjuvant setting. All subjects receiving at least one dose of the study drug(s) will be evaluable for toxicity.
Time Frame
42 months
Secondary Outcome Measure Information:
Title
Mean Treg cell staining percentage in harvested prostate tissues will be reported and compared post-treatment between the treatment groups using paired sample test.
Description
The standard deviation, 95% confidence interval, median, and range of values will also be reported where appropriate
Time Frame
42 months
Title
Pathological complete responses (pCR)- an absence of tumor identification on standard histological analysis of the resected prostate specimens.
Description
The estimate and 95% confidence intervals will be obtained.
Time Frame
42 months
Title
Undetectable PSA at 12 months- the proportion of patients who achieve an undetectable PSA (<0.1 ng/mL) by 12 months after prostatectomy
Description
The estimate and 95% confidence intervals will be obtained.
Time Frame
42 months
Title
PSA response rates- a 50% change in pre-treatment and post-treatment PSA.
Description
These endpoints will be expressed as the proportion of men achieving a PSA response. The estimate and 95% confidence intervals will be obtained.
Time Frame
42 months
Title
Time to PSA recurrence- the interval from the time of prostatectomy to the time when the first of at least two serial rises in PSA (≥2 weeks apart) with a PSA ≥0.2 ng/mL.
Description
PSA will be measured every 3 (±1) months during the first post-operative year and every 6 (±2) months during the second and third post-operative years. For subjects who have not yet demonstrated PSA relapse after 3 years followup patients will be censored at the date of the last assessment that shows a lack of PSA recurrence. This outcome will be expressed as a median (95% CI) and will be determined using the Kaplan-Meier method.
Time Frame
42 months

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate (clinical stage T1c-T3b, N0, M0) without involvement of lymph nodes, bone, or visceral organs Initial prostate biopsy is available for central pathologic review, and is confirmed to show at least 2 positive cores and a Gleason sum of ≥4+3 Radical prostatectomy has been scheduled at Columbia University Irving Medical Center Age ≥18 years Eastern Cooperative Oncology Group (ECOG) performance status 0-1, or Karnofsky score ≥ 70% (see Appendix A) Adequate bone marrow, hepatic, and renal function: White blood cell count (WBC) >3,000 cells/mm3 Absolute neutrophil count (ANC)>1,500 cells/mm3 Hemoglobin >9.0 g/dL Platelet count >100,000 cells/mm3 Serum creatinine <1.5 × upper limit of normal (ULN) Serum bilirubin <1.5 × ULN Alanine transaminase (ALT) <3 × ULN Aspartate aminotransferase (AST)<3 × ULN Alkaline phosphatase <3 × ULN Willingness to provide written informed consent and HIPAA authorization for the release of personal health information, and the ability to comply with the study requirements (note: HIPAA authorization will be included in the informed consent) Willingness to use barrier contraception from the time of first dose of BMS-986218 until 165 days from the last dose of BMS-986218. Exclusion Criteria: Presence of known lymph node involvement or distant metastases Other histologic types of prostate cancers such as ductal, sarcomatous, lymphoma, small cell, and neuroendocrine tumors Prior radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for prostate cancer Prior immunotherapy/vaccine therapy for prostate cancer Concomitant treatment with other hormonal therapy or 5α-reductase inhibitors (prior use of these agents is allowed). Conditions requiring systemic treatment with either corticosteroids > 10 mg daily prednisone equivalents or other immunosuppressive medications within 14 days of study treatment administration, except for adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease. (1) Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating study treatment is permitted. History of known or suspected autoimmune disease with the following exceptions: Vitiligo Resolved childhood atopic dermatitis Psoriasis (with exception of psoriatic arthritis) not requiring systemic treatment (within the past 2 years). Patients with Grave's disease or Hashimoto's thyroiditis that are now euthyroid clinically and by laboratory testing. History of malignancy within the last 2 years, with the exception of non-melanoma skin cancers and superficial bladder cancer Known uncontrolled or significant cardiovascular disease including, but not limited, to any of the following: Myocardial infarction or stroke/transient ischemic attack within the past 6 months. Uncontrolled angina within the past 3 months. Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes). History of other clinically significant heart disease (eg, cardiomyopathy, congestive heart failure with New York Heart Association functional classification III to IV, pericarditis, or significant pericardial effusion). History of myocarditis, regardless of etiology. Cardiovascular disease-related requirement for daily supplemental oxygen therapy. Known prior or current history of HIV. Patients with known untreated hepatitis B/C or those with a detectable viral load. Active infection ≤7 days prior to start of treatment. Live vaccine within 30 days of start of treatment. Prior history of hypersensitivity to a monoclonal antibody.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karie D. Runcie, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Columbia University Irving Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

Non-fucosylated Anti-CTLA-4 (BMS-986218) + Degarelix Acetate vs. Degarelix Acetate Alone in Men With High-risk Localized Prostate Cancer

We'll reach out to this number within 24 hrs