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BRIEF TITLE: A Phase II Trial of Hypofractionated Radiotherapy in Patients With Limited Progression on Immune Checkpoint Blockade

A Phase II Trial of Hypofractionated Radiotherapy in Patients With Limited Progression on Immune Checkpoint Blockade


  • Org Study ID: 18-359
  • Secondary ID:
  • NCT ID: NCT03693014
  • NCT Alias:
  • Sponsor: Memorial Sloan Kettering Cancer Center - Other
  • Source: Memorial Sloan Kettering Cancer Center

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.

Overal Status Start Date Phase Study Type
Recruiting October 1, 2018 Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: evaluate overall response rate (ORR)

Primary Outcome 1 - Time Frame: 24 weeks

Condition:

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

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 is receiving treatment with an immune checkpoint inhibitor including but not
limited to ipilimumab, nivolumab, avelumab, durvalumab, pembrolizumab, atezolizumab,
and tremelimumab. 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.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Yoshiya Yamada, MD

Role: Principal Investigator

Affiliation: Memorial Sloan Kettering Cancer Center

Overall Contact

Name: Yoshiya Yamada, MD

Phone: 212-639-2950

Email: yamadaj@mskcc.org

Link: Memorial Sloan Kettering Cancer Center

Locations

Facility Status Contact
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey 07920
United States
Recruiting Yoshiya Yamada, MD
212-639-2950
Memoral Sloan Kettering Monmouth
Middletown, New Jersey 07748
United States
Recruiting Yoshiya Yamada, MD
212-639-2950
Memorial Sloan Kettering Commack
Commack, New York 11725
United States
Recruiting Yoshiya Yamada, MD
212-639-2950
Memoral Sloan Kettering Westchester
Harrison, New York 10604
United States
Recruiting Yoshiya Yamada, MD
212-639-2950
Memorial Sloan Kettering Cancer Center
New York, New York 10065
United States
Recruiting Yoshiya Yamada, MD
212-639-2950
Memorial Sloan Kettering Rockville Centre
Rockville Centre, New York 11570
United States
Recruiting Yoshiya Yamada, MD
212-639-2950