Stereotactic Body Radiation Therapy, Nivolumab, and Urelumab or Cabiralizumab in Treating Participants with Metastases in Advanced Solid Tumors

Status: Active

Description

This phase I trial studies the side effects and best dose of stereotactic body radiation therapy when given together with nivolumab and urelumab or cabiralizumab in treating participants with solid tumors that have spread to other places in the body. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, urelumab, and cabiralizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving stereotactic body radiation therapy, nivolumab, and urelumab or cabiralizumab may work better in treating advanced solid tumors.

Eligibility Criteria

Inclusion Criteria

  • Participants must be able to give self-consent and then sign and date an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent in accordance with local regulatory and institutional guidelines; this consent must be obtained before the performance of any protocol-related procedures that are not considered part of normal participant care
  • Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
  • For biopsy identified participants: be willing to undergo repeat biopsy of a tumor lesion before and after treatment; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may be exempted from this requirement after consultation with the principal investigator; note: enforcement of biopsy requirement may come into effect for all participants depending on the state of accrual compared with number of obtained biopsies at any point in the study
  • Have a 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 non-small cell lung carcinoma (NSCLC) must have undergone EGFR and ALK testing and have received appropriate initial therapy
  • Participants must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, including at least one tumor lesion that meets criteria for multi-organ site ablative radiation therapy (MOSART) SBRT radiation * 0.25 cc to 65 cc of viable tumor (i.e. primary disease of metastases) approximately 5 cm in maximal dimension; tumors larger than 65 cc can be partially treated * Metastases located in lung, liver, mediastinal/cervical node, spinal/paraspinal, osseous, abdominal-pelvic (lymph node/adrenal gland)
  • Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
  • Absolute neutrophil count (ANC) >= 1,500/uL
  • Platelets >= 100 x 10^3/uL
  • Hemoglobin >= 8 g/dL without transfusion or erythropoietin (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); glomerular filtration rate (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 =< 5 x ULN for subjects with liver metastases
  • Albumin >= 3.4 mg/dL
  • Participants may have had prior immuno-oncology (IO) therapy (including but not limited to anti-CTLA4 and anti-PD1/L1) excluding prior CSF1R directed agents for the study arm containing cabiralizumab
  • Have an investigator determined life expectancy of at least 6 months
  • Participants who are women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 72 hours prior to the start of study drug
  • Participants who are women must not be breastfeeding
  • Participants who are WOCBP 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)
  • Participants who are WOCBP who are continuously not heterosexually active are exempted from contraceptive requirements but still must undergo pregnancy testing
  • Participants who are males and who are sexually active with WOCBP 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); in addition, male participants must be willing to refrain from sperm donation during this time
  • Participants who are azoospermic males are exempt from contraceptive requirements
  • Investigators shall counsel WOCBP, and male participants who are sexually active with WOCBP, on the importance of pregnancy prevention and the implications of an unexpected pregnancy; investigators shall advise on the use of highly effective methods of contraception, which have a failure rate of < 1% when used consistently and correctly

Exclusion Criteria

  • Participants 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
  • Participants 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
  • Participants 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 * Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study * Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • Participants must not have known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 2 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
  • Participants must not have had prior radiation therapy (defined as > 10% of prior prescription dose) to the area planning to be treated with SBRT
  • Participants 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
  • Participants must not have a known history of active TB (Bacillus tuberculosis)
  • Participants must not have hypersensitivity to nivolumab, urelumab, cabiralizumab or any of their excipients
  • Participants 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 principal investigator (PI)
  • Participants 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
  • Participants must not have a known history of non-infectious pneumonitis that required steroids for treatment
  • Participants must not have evidence of interstitial lung disease
  • Participants must not have an active infection requiring systemic therapy
  • Participants 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., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [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 * Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
  • 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
  • Participants must not have a history of allergy to nivolumab, urelumab or cabiralizumab
  • Participants 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)
  • Participants must not be prisoners or be involuntarily incarcerated
  • Participants must not be compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

Locations & Contacts

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: Active
Contact: Jason John Luke
Phone: 773-834-3096
Email: jluke@medicine.bsd.uchicago.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the recommended stereotactic body radiation therapy (SBRT) dose to various metastatic locations in participants with advanced solid tumors in conjunction with urelumab and nivolumab or cabiralizumab and nivolumab.

SECONDARY OBJECTIVES:

I. To estimate the rates of grade 3 or higher adverse events, by organ system, by Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 that occur within 3 months from the start of SBRT.

II. To estimate the rates of long-term adverse events (after 3 months) from the end of SBRT.

III. To summarize the response rate, progression-free and overall survival.

IV. To determine the local control of the SBRT treated lesion.

EXPLORATORY OBJECTIVES:

I. To determine the local control of SBRT treated lesions.

II. To explore potential association between biomarkers and clinical effect of combination immunotherapy/SBRT.

III. To calculate delivered radiation dose using cone-beam computed tomography (CT) images collected on the radiation treatment table in the final treatment position.

IV. To evaluate changes in the tumor microenvironment induced by radiation.

OUTLINE: Participants are assigned to 1 of 2 cohorts.

COHORT I: Participants undergo 3 or 5 fractions of stereotactic body radiation therapy over 1 week. Beginning day 1 of stereotactic body radiation therapy, participants receive nivolumab intravenously (IV) over 30 minutes and urelumab IV every 30 minutes once every 4 weeks in the absence of disease progression or unacceptable toxicity.

COHORT II: Participants undergo 3 or 5 fractions of stereotactic body radiation therapy over 1 week. Beginning day 1 of stereotactic body radiation therapy, participants receive nivolumab IV over 30 minutes once every 4 weeks and cabiralizumab IV over 30 minutes once every 2 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30, 60, and 100 days, every 12 weeks for 1 year, and then every 6 months for up to 2 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
University of Chicago Comprehensive Cancer Center

Principal Investigator
Jason John Luke

Trial IDs

Primary ID IRB17-1317
Secondary IDs NCI-2018-00338
Clinicaltrials.gov ID NCT03431948