Clinical Trials /

Stereotactic Body Radiotherapy (SBRT) Plus Immunotherapy for Cancer

NCT03431948

Description:

Study to determine the best dose of stereotactic body radiation therapy (SBRT) to be administered in combination with immunotherapy drugs including urelumab, cabiralizumab and nivolumab .

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Stereotactic Body Radiotherapy (SBRT) Plus Immunotherapy for Cancer
  • Official Title: Platform Phase 1 Study Investigating the Safety of Stereotactic Body Radiotherapy (SBRT) With Immuno-oncology Agents for the Treatment of Multiple Metastases in Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: IRB17-1317
  • SECONDARY ID: CA025-002
  • NCT ID: NCT03431948

Conditions

  • Cancer

Interventions

DrugSynonymsArms
NivolumabOPDIVO, BMS-936558SBRT with Nivolumab and Urelumab
CabiralizumabBMS-986227, FPA008SBRT with Nivolumab and Cabiralizumab
UrelumabBMS-663513SBRT with Nivolumab and Urelumab

Purpose

Study to determine the best dose of stereotactic body radiation therapy (SBRT) to be administered in combination with immunotherapy drugs including urelumab, cabiralizumab and nivolumab .

Trial Arms

NameTypeDescriptionInterventions
SBRT with Nivolumab and UrelumabExperimentalPatients will receive stereotactic body radiation therapy (SBRT) in combination with nivolumab and urelumab.
  • Nivolumab
  • Urelumab
SBRT with Nivolumab and CabiralizumabExperimentalPatients will receive stereotactic body radiation therapy (SBRT) in combination with nivolumab and cabiralizumab .
  • Nivolumab
  • Cabiralizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Willingness and ability to provide written informed consent

          -  Willingness and ability to comply with required study visits and procedures

          -  For Biopsy Patients: Willingness to undergo repeat biopsy of tumor before and after
             treatment

          -  Men or women ≥ 18 years of age.

          -  Histologically confirmed advanced solid tumor for which curative treatment is not
             available.

          -  Have undergone appropriate standard of care treatment options (in the opinion of the
             treating investigator). Participants with NSCLC must have undergone EGFR and ALK
             testing and have received appropriate initial therapy.

          -  Measurable disease, including at least one tumor lesion that meets criteria for
             multi-organ site ablative radiation therapy (MOSART) SBRT radiation.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1

          -  Adequate organ function, as defined by the following:

          -  Absolute neutrophil count (ANC) ≥ 1,500/µL

          -  Platelets ≥ 100 x 10^3/µL

          -  Hemoglobin ≥ 8 g/dL without transfusion or EPO dependency

          -  Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) OR measured or
             calculated creatinine clearance (CrCL) > 50 mL/min (creatinine clearance should be
             calculated per institutional standard). GFR can also be used in place of creatinine of
             CrCl.

          -  Serum total bilirubin ≤1.5 x institutional ULN (except subjects with Gilbert's
             Syndrome, who must have normal direct bilirubin).

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x
             institutional ULN OR ≤ 5x ULN for subjects with liver metastases.

          -  Albumin > 3.2 mg/dL.

          -  Prior immuno-oncology (IO) therapy

          -  Have a physician determined life expectancy of at least 6 months.

          -  Negative pregnancy test for women of childbearing potential (WOCBP) within 72 hours of
             starting therapy

          -  Must not be breastfeeding

          -  Woman of childbearing potential: Must agree to follow instructions for method(s) of
             contraception for the duration of treatment with study drug(s) and up to 5 months post
             last dose of study drug(s).

          -  Men: Must agree to follow instructions for method(s) of contraception for the duration
             of treatment with study drug(s) and up to 7 months post last dose of study drug(s).
             Must be willing to refrain from sperm donation during this time.

        Exclusion Criteria:

          -  Must not be currently receiving study therapy or have participated in a study of an
             investigational agent and received study therapy or used an investigational device
             within 4 weeks of the first dose of treatment.

          -  Must not have had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior
             to study Day 1 or have not recovered (i.e. < grade 1 at baseline) from adverse events
             due to agents administered more than 4 weeks earlier.

          -  Must not have had prior chemotherapy, targeted small molecule therapy, radiation or
             other anti-cancer therapy (with exceptions for disease-specific hormone treatments
             considered standard of care) within 2 weeks prior to study Day 1 or have not recovered
             (i.e. < grade 1 or at baseline) from adverse events due to a previously administered
             agent. Exception for ≤ grade 2 neuropathy. If patient received major surgery, they
             must have recovered adequately from the toxicity and/or complications from the
             intervention prior to starting therapy.

          -  Must not have known active central nervous system (CNS) metastases and/or
             carcinomatous meningitis. Patients with previously treated brain metastases may
             participate provided they are stable, have no evidence of new or enlarging brain
             metastases, and are not using steroids for at least 7 days prior to trial treatment.

          -  Must not have had prior radiation therapy (defined as >10% of prior prescription dose)
             to the area planning to be treated with SBRT.

          -  Must not have a diagnosis of immunodeficiency or is receiving systemic steroid therapy
             at a dose of >10 mg prednisone daily or equivalent at time of first dose of trial
             treatment.

          -  Must not have a known history of active TB (Bacillus Tuberculosis)

          -  Must not have hypersensitivity to nivolumab, urelumab, cabiralizumab or any of their
             excipients.

          -  Must not have a known additional malignancy that could confuse analysis of on-study
             treatment. Inclusion of all study participants with more than one malignancy must be
             discussed and approved by the PI.

          -  Must not have active autoimmune disease that has required systemic treatment in the
             past 2 years (i.e. with use of disease modifying agents, corticosteroids or
             immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic
             corticosteroids replacement therapy for adrenal or pituitary insufficiency, etc.) is
             not considered a form of systemic treatment.

          -  Must not have a known history of non-infectious pneumonitis that required steroids for
             treatment.

          -  Must not have evidence of interstitial lung disease.

          -  Must not have an active infection requiring systemic therapy.

          -  Must not have a history 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 known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Is pregnant or breastfeeding, or expecting to 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.

          -  If known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected) then patient is not eligible for cohorts including SBRT to
             liver lesions.

          -  Participants must not have had prior organ allograft or allogeneic bone marrow
             transplantation.

          -  Participants must not have had 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, significant pericardial effusion, or
                  myocarditis)

               -  Cardiovascular disease-related requirement for daily supplemental oxygen therapy

          -  Has received a live vaccine within 30 days of planned start of study therapy.

          -  Participants may not concomitantly use statins while on study. However, a patient
             using statins for over 3 months prior to study drug administration and in stable
             status without CK rise may be permitted to enroll.

          -  Participants may not have current or history of clinically significant muscle
             disorders (eg, myositis), recent unresolved muscle injury, or any condition known to
             elevate serum CK levels.

          -  Must not have a history of allergy to nivolumab, urelumab or cabiralizumab.

          -  Must not have a history of any significant drug allergy (such as anaphylaxis or
             hepatotoxicity) to prior anti-cancer immune-modulating therapies (eg, checkpoint
             inhibitors and T-cell co-stimulatory antibodies).

          -  Must not be prisoners or be involuntarily incarcerated.

          -  Must not be compulsorily detained for treatment of either a psychiatric or physical
             (eg, infectious disease) illness.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Recommended dose of SBRT given in combination with immunotherapy
Time Frame:3 months
Safety Issue:
Description:Dose of stereotactic body radiation therapy (SBRT) that can safety be given with immunotherapy.

Secondary Outcome Measures

Measure:Rates of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher side effects
Time Frame:3 months
Safety Issue:
Description:Rate of side effects seen in study participants.
Measure:Rates of long term side effects
Time Frame:6 - 24 months
Safety Issue:
Description:Rate of long term (occurring 6 month or more after treatment) side effects seen in study participants.
Measure:Response rate
Time Frame:6 months
Safety Issue:
Description:Rates of response (tumor shrinkage).
Measure:Progression free survival rate
Time Frame:6 months
Safety Issue:
Description:Number of participants that do not have disease worsening.
Measure:Overall survival rate
Time Frame:6 - 24 months
Safety Issue:
Description:Number of participants still alive.
Measure:Local disease control of SBRT treated lesions
Time Frame:6 months
Safety Issue:
Description:Rate of disease control (tumor shrinkage) of radiation treated lesions.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Chicago

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