Radiation Therapy and M7824 in Treating Patients With Metastatic Hormone Receptor Positive, HER2 Negative Breast Cancer
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|ClinicalTrials.gov Identifier: NCT03524170|
Recruitment Status : Recruiting
First Posted : May 14, 2018
Last Update Posted : November 19, 2020
|Condition or disease||Intervention/treatment||Phase|
|Anatomic Stage IV Breast Cancer AJCC v8 Metastatic Breast Carcinoma Prognostic Stage IV Breast Cancer AJCC v8||Drug: Bintrafusp Alfa Radiation: Radiation Therapy||Phase 1|
I. To determine the recommended phase II dose (RP2D) of M7824 and radiation therapy in patients with metastatic hormone receptor positive (HR+)/HER2 negative (-) breast cancer.
II. To evaluate the safety and tolerability of M7824 and radiation therapy in patients with metastatic HR+/HER2- breast cancer.
I. To assess immunologic/molecular responses, specifically percentage (%) change in tumor-infiltrating lymphocytes (TIL) pre and post therapy to M7824 and radiation therapy in patients with HR+/HER2- metastatic breast cancer.
II. To explore progression free survival (PFS) and overall survival (OS) to power future definitive trial.
III. To evaluate the in-field and abscopal effect of treatment with anti-PD-L1/TGF-beta trap (M7824) and radiation therapy.
I. To characterize the effect of anti-PD-L1/TGF-beta trap (M7824) and radiation therapy on immune biomarkers including PD-L1 expression and fibrosis changes in tumor microenvironment in tumor tissue obtained from subjects pre- and post-treatment.
II. To characterize circulating immune cell populations and cytokine profiles in tumor and circulation following treatment with M7824.
III. To conduct ribonucleic acid sequencing (RNAseq), RNA Scope, whole exome sequencing (WES) targeted sequencing and tissue IO gene expression.
Patients receive M7824 intravenously (IV) over 1 hour every 14 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Beginning within 3 days after second dose of M7824, patients undergo radiation therapy once a day (QD) for 5-10 days depending on the site of disease in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up for 90 days.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||RACHEL1: A Phase I Radiation and Checkpoint Blockade Trial in Patients With Metastatic Hormone Receptor Positive, HER2 Negative Breast Cancer|
|Actual Study Start Date :||April 30, 2018|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||December 31, 2020|
Experimental: Treatment (M7824, radiation therapy)
Patients receive M7824 IV over 1 hour every 14 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Beginning within 3 days after second dose of M7824, patients undergo radiation therapy QD for 5-10 days depending on the site of disease in the absence of disease progression or unacceptable toxicity.
Drug: Bintrafusp Alfa
Radiation: Radiation Therapy
Undergo radiation therapy
- Recommended phase II dose (RP2D) of M7824 and radiation therapy in patients with metastatic HR+/HER2- breast cancer [ Time Frame: 6 weeks after first administration of M7824 ]Will be determined by dose limiting toxicity. RP2D defined as the highest dose level with no more than 1 patient with DLT out of 6 patients that are treated.
- Safety and tolerability in patients with metastatic HR+/HER2- breast cancer [ Time Frame: Start of study drug up to 30 days after study drug stopped ]Will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03. Recommended phase 2 dose (RP2D) will be determined by "3+3" design, and the recommended phase II dose is defined when 6 patients have been treated on that dose with no more than 1 dose limiting toxicity (DLT). DLT will be evaluated within 6 weeks after first administration of anti-PD-L1/TGFbetaRII fusion protein M7824 (M7824). Detailed information collected for each adverse event (AE) will include a description of the event, duration, severity, relationship to study treatment, action taken, and clinical outcome. Severity of AEs will be graded according to the CTCAE v 4.0. Summary of AEs will include only AEs that started or worsened during the on-treatment period, the treatment-emergent AEs. However, all safety data (including those from the pre- and post-treatment periods) will be listed and those collected during the pre- and post-treatment are to be flagged.
- Progression-free survival (PFS) [ Time Frame: Start of study drug up to 90 days after study drug stopped ]PFS is defined as the time from treatment until objective tumor progression or death, whichever occurs first.
- Overall survival (OS) [ Time Frame: Start of study drug up to 90 days after study drug stopped ]OS is defined as the time from treatment until death from any cause.
- Immunologic/molecular response [ Time Frame: Up to 56 days ]Immunologic/molecular response is defined as % change in tumor infiltrating lymphocytes (TIL) pre and post therapy to M7824 and radiation therapy in patients with HR+/HER2- metastatic breast cancer.
- Evaluation of the size of metastasis after treatment with M7824 with radiation (in-field) and non-irradiated (abscopal) sites [ Time Frame: Up to 56 days ]Will be determined by Response Evaluation Criteria in Solid Tumors 1.1 criteria.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03524170
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Jennifer K. Litton 713-792-2817 email@example.com|
|Principal Investigator: Jennifer K. Litton|
|Principal Investigator:||Jennifer K Litton||M.D. Anderson Cancer Center|