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
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
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.
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).
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:
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
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