Stereotactic Body Radiotherapy (SBRT) Plus Immunotherapy for Cancer

NCT03431948 | Completed Phase 1 FDA Drug

• 2 other identifiers: IRB17-1317CA025-002
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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 .

Conditions

Cancer

Outcome Measures

Primary Outcomes (1)

• Recommended dose of SBRT given in combination with immunotherapy

  Dose of stereotactic body radiation therapy (SBRT) that can safety be given with immunotherapy.

  3 months

Secondary Outcomes (6)

• Rates of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher side effects

  3 months

• Rates of long term side effects

  6 - 24 months

• Response rate

  6 months

• Progression free survival rate

  6 months

• Overall survival rate

  6 - 24 months

Study Arms (2)

SBRT with Nivolumab and Urelumab

EXPERIMENTAL

Patients will receive stereotactic body radiation therapy (SBRT) in combination with nivolumab and urelumab.

Drug: Nivolumab; Drug: Urelumab; Radiation: Stereotactic Body Radiation Therapy

SBRT with Nivolumab and Cabiralizumab

EXPERIMENTAL

Patients will receive stereotactic body radiation therapy (SBRT) in combination with nivolumab and cabiralizumab .

Drug: Nivolumab; Drug: Cabiralizumab; Radiation: Stereotactic Body Radiation Therapy

Interventions

Nivolumab DRUG

Nivolumab 240 mg given by intravenous infusion every 2 weeks

Also known as: OPDIVO, BMS-936558

SBRT with Nivolumab and Cabiralizumab; SBRT with Nivolumab and Urelumab

Cabiralizumab DRUG

Cabiralizumab 4 mg/kg given by intravenous infusion every 2 weeks

Also known as: BMS-986227, FPA008

SBRT with Nivolumab and Cabiralizumab

Urelumab DRUG

Urelumab 8 mg given by intravenous infusion every 4 weeks

Also known as: BMS-663513

SBRT with Nivolumab and Urelumab

Stereotactic Body Radiation Therapy RADIATION

Radiation to metastatic lesion(s) given at assigned dose levels based on lesion location and dose level being tested at time of enrollment. Doses range from 30 - 50 Gy.

SBRT with Nivolumab and Cabiralizumab; SBRT with Nivolumab and Urelumab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• University of Chicago: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Nivolumab; cabiralizumab; urelumab; Radiosurgery

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jason Luke, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Patients will be enrolled in parallel based on physician preference and slot availability.

Study Record Dates

• First Submitted: February 7, 2018
• First Posted: February 13, 2018
• Study Start: March 15, 2018
• Primary Completion: February 29, 2020
• Study Completion: April 11, 2022
• Last Updated: February 16, 2023

Record last verified: 2023-02

Locations

US (1)