Stereotactic Body Radiation Therapy With REGN2810 and/or Ipilimumab Before Surgery in Treating Participants With Progressive Advanced or Oligometastatic Prostate Cancer

NCT03477864 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 17G.508JT 10817
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase I trial studies the side effects of anti-PD-1 monoclonal antibody REGN2810 (REGN2810) and/or ipilimumab when given together with stereotactic body radiation therapy before surgery in treating participants with prostate cancer that is growing, spreading, or getting worse, and has spread to other places in the body, or formed a small number of new tumors in one or two other parts of the body. Monoclonal antibodies, such as anti-PD-1 monoclonal antibody REGN2810 and ipilimumab, may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may cause less damage to normal tissue. Giving anti-PD-1 monoclonal antibody REGN2810 and ipilimumab with stereotactic body radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Conditions

Stage III Prostate Cancer; Stage IIIA Prostate Cancer; Stage IIIB Prostate Cancer; Stage IIIC Prostate Cancer; Stage IV Prostate Cancer; Stage IVA Prostate Cancer; Stage IVB Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 criteria

  Will be assessed by quantifying the toxicities and grades 3 and 4 experienced by subjects who have received REGN2810 + ipilimumab in combination with radiation therapy, including serious adverse events (SAEs) and events of clinical interest (ECIs). Time-to-event continual reassessment (TITE-CRM) design will be used to confirm the safety of the treatments based on toxicities.

  Up to 70 days

Secondary Outcomes (3)

• Overall pathologic response rate

  Up to 2 years

• Prostate specific antigen (PSA) progression free survival

  Up to 2 years

• Radiographic progression free survival

  Up to 2 years

Study Arms (3)

Arm A (REGN2810, SBRT, surgery)

EXPERIMENTAL

Participants receive anti-PD-1 monoclonal antibody REGN2810 IV over 30 minutes on day 1 of week 1 and in week 4, and undergo SBRT for 4 fractions on days 2-5 of week 3. Within 14-21 days, participants undergo radical prostatectomy.

Radiation: Stereotactic Body Radiation Therapy (SBRT); Procedure: Radical Prostatectomy; Biological: Anti-PD-1 Monoclonal Antibody REGN2810

Arm B (ipilimumab, SBRT, surgery)

EXPERIMENTAL

Participants receive ipilimumab via intraprostatic injection on day 1 of week 1, and undergo SBRT for 4 fractions on days 2-5 of week 3. Within 14-21 days, participants undergo radical prostatectomy.

Biological: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT); Procedure: Radical Prostatectomy

Arm C (REGN2810, ipilimumab, SBRT, surgery)

EXPERIMENTAL

Participants receive anti-PD-1 monoclonal antibody REGN2810 as in Arm A and ipilimumab as in Arm B. Participants also undergo SBRT for 4 fractions on days 2-5 of week 3. Within 14-21 days, participants undergo radical prostatectomy.

Biological: Ipilimumab; Radiation: Stereotactic Body Radiation Therapy (SBRT); Procedure: Radical Prostatectomy; Biological: Anti-PD-1 Monoclonal Antibody REGN2810

Interventions

Ipilimumab BIOLOGICAL

Given via intraprostatic injection

Also known as: 477202-00-9, 720801, Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Yervoy, MDX-CTLA4, MDX-010

Arm B (ipilimumab, SBRT, surgery); Arm C (REGN2810, ipilimumab, SBRT, surgery)

Stereotactic Body Radiation Therapy (SBRT) RADIATION

Undergo SBRT

Arm A (REGN2810, SBRT, surgery); Arm B (ipilimumab, SBRT, surgery); Arm C (REGN2810, ipilimumab, SBRT, surgery)

Radical Prostatectomy PROCEDURE

Undergo radical prostatectomy

Also known as: Prostatovesiculectomy

Arm A (REGN2810, SBRT, surgery); Arm B (ipilimumab, SBRT, surgery); Arm C (REGN2810, ipilimumab, SBRT, surgery)

Anti-PD-1 Monoclonal Antibody REGN2810 BIOLOGICAL

Given IV

Arm A (REGN2810, SBRT, surgery); Arm C (REGN2810, ipilimumab, SBRT, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent for the trial
• Have progressive advanced prostate cancer based on at least one of the following criteria:
• Gleason score of ≥ 7
• Any PSA
• TNM clinical stage T3-T4, N1
• Oligometastatic prostate cancer patients who have not received primary therapy are eligible; (oligometastatic disease is defined as a patient with ≤ 3 metastatic bone lesions on the bone scan or tissue metastasis)
• To be scheduled for a Radical Prostatectomy
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) ≥ 1000 /mcL within 7 days of treatment initiation
• Platelets ≥ 150,000 / mcL within 7 days of treatment initiation
• Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L within 7 days of treatment initiation
• Lymphocytes ≥ 500 / mcL within 7 days of treatment initiation
• Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) ≥ 50 mL/min for subject with creatinine levels \> 1.5 X institutional ULN within 7 days of treatment initiation
• \* Glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl
• Serum total bilirubin ≤ 1.5 X ULN within 7 days of treatment initiation

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment
• Prior treatment with an agent that blocks PD-1/PD-L1 pathway or other immune modulating agents within fewer than 4 weeks of 4 half-lives
• Has a diagnosis of immunodeficiency or is receiving any systemic steroid therapy or any form of immunosuppressive therapy within 7 days prior to day 1 of trial treatment
• Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Has had prior treatment with idelalisib
• Has had prior or current treatment with Androgen Deprivation Therapy
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Note: Subjects with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial urothelial cancer, or superficial bladder cancer that has undergone potentially curative therapy
• Has an active autoimmune disease requiring systemic treatment within the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
• Has evidence of interstitial lung disease, active, non-infectious pneumonitis
• Has evidence of significant liver disease
• Has an active infection requiring systemic therapy; prior to dosing with REGN2810 the subject must be at least 5 half-lives from their last dose of antibiotic
• Has a history of listeriosis or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• Prostate Cancer Foundation: collaborator
• Regeneron Pharmaceuticals: collaborator

Related Links

• Thomas Jefferson University Hospital

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Ipilimumab; CTLA-4 Antigen; Radiosurgery; cemiplimab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Adam Dicker, MD

  Sidney Kimmel Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2018
• First Posted: March 26, 2018
• Study Start: December 24, 2018
• Primary Completion: November 4, 2019
• Study Completion: November 4, 2019
• Last Updated: April 29, 2025

Record last verified: 2025-04