Clinical Trials /

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

NCT03477864

Description:

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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Stereotactic Body Radiation Therapy With REGN2810 and/or Ipilimumab Before Surgery in Treating Participants With Progressive Advanced or Oligometastatic Prostate Cancer
  • Official Title: R2810-ONC-16XX: A Phase 1 Neoadjuvant Study of Stereotactic Body Radiation Therapy With Systemic REGN2810 and Intraprostatic Ipilimumab, Alone or in Combination, in Patients With Locally Advanced Prostate Cancer Prior to Radical Prostatectomy

Clinical Trial IDs

  • ORG STUDY ID: 17G.508
  • NCT ID: NCT03477864

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

Interventions

DrugSynonymsArms
Ipilimumab477202-00-9, 720801, Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Yervoy, MDX-CTLA4, MDX-010Arm B (ipilimumab, SBRT, surgery)
Anti-PD-1 Monoclonal Antibody REGN2810Arm A (REGN2810, SBRT, surgery)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the safety and tolerability for an established effective dose of systemic
      REGN2810 and intraprostatic ipilimumab with stereotactic body radiation therapy (SBRT) in
      patients with locally advanced prostate cancer with or without oligometastatic disease.

      SECONDARY OBJECTIVES:

      I. To determine overall pathologic response rate after radical prostatectomy. II. To
      determine prostate-specific antigen (PSA) progression free survival in men treated with
      REGN2810 and intraprostatic ipilimumab with SBRT.

      III. To determine radiographic progression free survival in men treated with REGN2810 and
      intraprostatic ipilimumab with SBRT.

      IV. Acute and chronic adverse events (AEs).
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (REGN2810, SBRT, surgery)ExperimentalParticipants 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.
  • Anti-PD-1 Monoclonal Antibody REGN2810
Arm B (ipilimumab, SBRT, surgery)ExperimentalParticipants 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.
  • Ipilimumab
Arm C (REGN2810, ipilimumab, SBRT, surgery)ExperimentalParticipants 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.
  • Ipilimumab
  • Anti-PD-1 Monoclonal Antibody REGN2810

Eligibility Criteria

        Inclusion Criteria:

          -  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

             * Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN within 7
             days of treatment initiation

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 X
             ULN within 7 days of treatment initiation

          -  International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 X ULN unless
             subject is receiving anticoagulant therapy as long as PT or INR is within therapeutic
             range of intended use of anticoagulants within 7 days of treatment initiation

          -  Activated partial thromboplastin time (aPTT) ≤ 1.5 X ULN unless subject is receiving
             anticoagulant therapy as long as aPTT is within therapeutic range of intended within 7
             days of treatment initiation

        Exclusion Criteria:

          -  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

          -  Has psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial

          -  Has a contraindication to administration of amoxicillin, ampicillin, ciprofloxacin,
             erythromycin, gentamycin, penicillin, trimethoprim/sulfamethoxazole, and vancomycin

          -  Is expecting to spontaneously conceive or father children within the projected
             duration of the trial, starting with the screening visit through 120 days after the
             last dose of trial treatment

          -  Has contraindication to administration of non-steroidal anti-inflammatory drugs
             (NSAIDS)

          -  Is or has an immediate family member (spouse or children) who is investigational site
             or staff directly involved with this trial, unless prospective Institutional Review
             Board (IRB) approval (by chair or designee) is given allowing exception to this
             criterion for a specific subject
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 criteria
Time Frame:Up to 70 days
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Overall pathologic response rate
Time Frame:Up to 2 years
Safety Issue:
Description:Will be presented with appropriate confidence intervals (95%, unless otherwise specified).
Measure:Prostate specific antigen (PSA) progression free survival
Time Frame:Up to 2 years
Safety Issue:
Description:Will be estimated using the Kaplan-Meier method.
Measure:Radiographic progression free survival
Time Frame:Up to 2 years
Safety Issue:
Description:Will be estimated using the Kaplan-Meier method.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Cancer Center at Thomas Jefferson University

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