A Study of Several Radiation Doses for Patients With Progression on Immunotherapy/Checkpoint Inhibitors

NCT03693014 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 18-359
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 10

Brief Summary

Drugs called checkpoint inhibitors help the immune system fight cancer. When the effectiveness of these drugs wears off, it may be possible to renew their effectiveness by combining it with a special type of radiation therapy called stereotactic body radiation therapy (SBRT). SBRT is a commonly used type of radiation therapy that gives high dose radiation with high precision to tumors in 1-5 treatments. Radiation therapy, such as SBRT can also treat sites of metastases. The use of checkpoint inhibitors in combination with SBRT has been suggested to improve the immune response against cancer but has not been tested in a formal clinical trial. Up to three lesions can be treated with SBRT. This study only allows checkpoint inhibitors that are already approved by the Federal Drug Agency (FDA) for the treatment of your disease. All radiation therapy will be done on machines which are FDA approved.

Conditions

Metastatic Cancer; Melanoma Cancer; Lung Cancer; Bladder Cancer; Renal Cancer; Head/Neck Cancers

Keywords

Radiation; Immunotherapy/Checkpoint Inhibitors; 18-359

Outcome Measures

Primary Outcomes (1)

• evaluate overall response rate (ORR)

  in non-irradiated lesions during the first 24 weeks after treatment initiation as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in patients with limited progression receiving hypofractionated radiotherapy. ORR rate is defined as the number of patients treated to a given arm with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the total number of patients.

  24 weeks

Study Arms (1)

Stereotactic Body Radiotherapy

EXPERIMENTAL

Image Guided, Stereotactic Body Radiotherapy (27 Gy over 3 fractions) to 1-3 lesions. Treatment with the checkpoint inhibitor will continue until progression at the discretion of the treating physician or unacceptable toxicity.

Radiation: Stereotactic Body Radiotherapy; Biological: Ipilimumab, Nivolumab, Pembrolizumab or Atezolizumab

Interventions

Stereotactic Body Radiotherapy RADIATION

(27 Gy over 3 fractions)

Stereotactic Body Radiotherapy

Ipilimumab, Nivolumab, Pembrolizumab or Atezolizumab BIOLOGICAL

The checkpoint inhibitor that the patient was already receiving should be continued according to the standard schedule and dose of administration as determined by the treating physician. Immune Checkpoint Inhibitors include Ipilimumab (Melanoma) Nivolumab (Melanoma, Renal, NSCLC), Pembrolizumab (Melanoma, NSCLC), Atezolizumab (Bladder)

Stereotactic Body Radiotherapy

Eligibility Criteria

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

You may qualify if:

• Subjects must have signed and dated an IRB approved written informed consent form in accordance with regulatory and institutional guidelines.
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other study obligations.
• Males and females ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Histologically confirmed metastatic cancer of any histology for which there is an FDA indication for an immune checkpoint inhibitor including melanoma, lung, bladder, renal and head/neck cancers.
• Patient has been receiving treatment with an immune checkpoint inhibitor including but not limited to ipilimumab, nivolumab, avelumab, durvalumab, pembrolizumab, atezolizumab, and tremelimumab for at least 2 months. A combination of these therapies is also permitted. No max prior lines of therapy.
• Patient has evidence of limited progression (up to 5 lesions either new or increase in at least 25% in the cross-sectional diameter of a known lesion) on most recent systemic imaging as determined by the treating physician. Patients with greater than 5 lesions can be included after discussion with the study investigators.
• Patient must be eligible to continue to receive an immune checkpoint inhibitor after radiotherapy.
• Subjects must have at least two lesions:
• One lesion must be safely amenable to irradiation in the opinion of the treating radiation oncologist. This can be a lesion that was previously irradiated if it is deemed appropriate by the treating physician and principal investigator. Standard MSKCC re-irradiation dose constraints must be met.
• At least one, not-to-be-irradiated lesion measurable by CT or MRI per RECIST 1.1 criteria.
• Prior palliative or curative radiotherapy must be completed at least 14 days prior to treatment.
• Immunosuppressive doses of systemic medication, such as steroids or absorbed topical steroids (doses \>10mg/day prednisone or equivalent) must be discontinued at least 14 days prior to radiotherapy administration.
• Women of childbearing potential must have a negative serum within 7 days prior to treatment, or urine pregnancy test (within 24 hours) (minimum sensitivity 25 IU/L or equivalent units of HCG). Women of childbearing potential must agree to follow instructions for method(s) of contraception from time of enrollment for the duration of treatment.
• Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year.

You may not qualify if:

• Active brain metastases (untreated brain metastases or growth on imaging as defined below) or leptomeningeal disease are not allowed. Subjects with brain metastases are eligible if these have been treated and there is no MRI (or CT if MRI contraindicated) evidence of progression for at least 8 weeks after treatment for these metastases is complete and within 28 days prior to first study treatment.
• Any medical disorder that, in the opinion of the investigator, might increase the risk associated with study participation or interferes with the interpretation of study results.
• Prior active malignancy within the previous 3 years except for locally curable cancers such as basal or squamous skin cancer, superficial bladder, low risk prostate cancer, breast, or cervix cancer. If other prior malignancy was active within prior 3 years, enrollment requires approval of a principal investigator.
• Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Subjects requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents for greater than 5 days) or other immunosuppressive medications within 14 days of study drug administration should be excluded. Inhaled or topical steroids and adrenal replacement doses \>10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Treatment with any other chemotherapy, radiation therapy, biologics for cancer, or investigational therapy concurrently or within 14 days of enrollment
• History of allergy to checkpoint inhibitors
• History of severe hypersensitivity reaction to any monoclonal antibody.
• Women must not be breastfeeding.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (10)

Hartford Healthcare

Hartford, Connecticut, 06102, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Rockville Centre

Rockville Centre, New York, 11570, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Lehigh Valley Health Network

Allentown, Pennsylvania, 18103, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Neoplasm Metastasis; Lung Neoplasms; Urinary Bladder Neoplasms; Kidney Neoplasms

Interventions

Radiosurgery; Ipilimumab; Nivolumab; pembrolizumab; atezolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Kidney Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Yoshiya Yamada, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open label Phase 2 screening trial in subjects.

Study Record Dates

• First Submitted: October 1, 2018
• First Posted: October 2, 2018
• Study Start: October 1, 2018
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: October 6, 2025

Record last verified: 2025-10

Locations

US (10)