Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Durvalumab

Tremelimumab

Antineoplastic Agents, Immunological

Subjects will get either whole brain radiation treatment (WBRT) or stereotactic radiosurgery (SRS), as per standard of care, with tremelimumab administered every 28 days. Patients, for whom concurrent HER2 directed therapy trastuzumab is indicated, as determined by the treating investigator, will be enrolled in a parallel HER2 directed therapy trastuzumab safety cohort. Protocol Expansion: Dose 1 of tremelimumab \& durvalumab (75 mg \& 1500 mg, respectively) will ideally be administered 2 days prior to initiation of brain radiotherapy (or between 5 days prior \& 3 days after initiation of radiotherapy). Subjects will get either WBRT or SRS, depending on the number \& size of their brain metastases. Following the 1st dose, tremelimumab \& duvralumab will be administered q28 days from the date of 1st tremelimumab \& durvalumab administration, plus or minus 1 week, for 4 cycles. After the 4th cycle, durvalumab will be administered alone until progression of disease or unacceptable toxicity.

Brain radiotherapy or Stereotactic Radiosurgery

HER2 directed therapy

Shanu Modi, MD

The purpose of this study is to see if the combination of tremelimumab and durvalumab with brain radiation therapy can help treat this type of breast cancer that has spread to the brain.

A Simon 2-stage single-arm design (n=17) will be employed to evaluate for preliminary efficacy. A maximum of 17 subjects will be accrued to the efficacy arm. After the first 3 patients are enrolled in the efficacy arm, a 6 week enrollment hold will be conducted in order to ensure safety before additional patients are enrolled. An interim assessment will then occur after the first 9 subjects have enrolled, and the accrual to this arm will proceed only if a pre-specified futility threshold is met. Patients not requiring continuation of HER2 directed therapy, such as trastuzumab, will be enrolled in this arm.

Brain Irradiation and Tremelimumab in Metastatic Breast Cancer

A Pilot Study of Brain Irradiation and Tremelimumab in Metastatic Breast Cancer

will be defined as the time from the first dose of tremelimumab until death or progressive disease, as measured by irRC. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

safety profile assessed with regular physical examination and toxicity assessment using the NCI CTCAE 4.0. Subjects will be followed with regular radiation oncology assessments as per the standard of care.

MedImmune LLC

Memorial Sloan Kettering Cancer Center

Subjects will get either whole brain radiation treatment (WBRT) or stereotactic radiosurgery (SRS), as per standard of care, with tremelimumab administered every 28 days. Patients, for whom concurrent HER2 directed therapy trastuzumab is indicated, as determined by the treating investigator, will be enrolled in a parallel HER2 directed therapy trastuzumab safety cohort.

Radiation and Tremelimumab

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Shanu Modi, MD

Progression Free Survival (irPFS)

Subjects will get either whole brain radiation treatment (WBRT) or stereotactic radiosurgery (SRS), as per standard of care, with tremelimumab administered every 28 days. Patients, for whom concurrent HER2 directed therapy trastuzumab is indicated, as determined by the treating investigator, will be enrolled in a parallel HER2 directed therapy trastuzumab safety cohort. Protocol Expansion: Dose 1 of tremelimumab \& durvalumab (75 mg \& 1500 mg, respectively) will ideally be administered 2 days prior to initiation of brain radiotherapy (or between 5 days prior \& 3 days after initiation of radiotherapy). Subjects will get either WBRT or SRS, depending on the number \& size of their brain metastases. Following the 1st dose, tremelimumab \& duvralumab will be administered q28 days from the date of 1st tremelimumab \& durvalumab administration, plus or minus 1 week, for 4 cycles. After the 4th cycle, durvalumab will be administered alone until progression of disease or unacceptable toxicity.

Brain radiotherapy or Stereotactic Radiosurgery

Tremelimumab

HER2 directed therapy

Durvalumab

Participants Assessed for Toxicity Using the NCI CTCAE 4.0

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Brain Irradiation and Tremelimumab in Metastatic Breast Cancer	NCT02563925	Metastatic Brea...	Brain radiother... Tremelimumab HER2 directed t... Durvalumab	18 Years -	Memorial Sloan Kettering Cancer Center
Brain Irradiation and Tremelimumab in Metastatic Breast Cancer	NCT02563925	Metastatic Brea...	Brain radiother... Tremelimumab HER2 directed t... Durvalumab	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for brain radiotherapy or stereotactic radiosurgery