Clinical Trials /

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

NCT03693014

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Several Radiation Doses for Patients With Progression on Immunotherapy/Checkpoint Inhibitors
  • Official Title: A Phase II Trial of Hypofractionated Radiotherapy in Patients With Limited Progression on Immune Checkpoint Blockade

Clinical Trial IDs

  • ORG STUDY ID: 18-359
  • NCT ID: NCT03693014

Conditions

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

Interventions

DrugSynonymsArms
Ipilimumab, Nivolumab, Pembrolizumab or AtezolizumabStereotactic Body Radiotherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Stereotactic Body RadiotherapyExperimentalImage 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.
  • Ipilimumab, Nivolumab, Pembrolizumab or Atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  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.

        Notes:

          -  Women who are not of childbearing potential i.e., who are postmenopausal or surgically
             sterile as well as azoospermia men do not require contraception.

          -  Azoospermic males, and women of childbearing potential who are continuously not
             heterosexually active, are exempt from contraceptive requirements. However, they still
             must have a pregnancy test.

          -  Exclusion Criteria:

               -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:evaluate overall response rate (ORR)
Time Frame:24 weeks
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Radiation
  • Immunotherapy/Checkpoint Inhibitors
  • 18-359

Last Updated

March 20, 2019