Immunotherapy (NHS-IL12 & Bintrafusp Alfa) and Radiation Therapy for the Treatment of Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer, the REINA Trial
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|ClinicalTrials.gov Identifier: NCT04756505|
Recruitment Status : Recruiting
First Posted : February 16, 2021
Last Update Posted : October 27, 2021
|Condition or disease||Intervention/treatment||Phase|
|Anatomic Stage IV Breast Cancer AJCC v8 Hormone Receptor Positive Breast Adenocarcinoma Metastatic Breast Carcinoma Metastatic HER2 Negative Breast Adenocarcinoma Prognostic Stage IV Breast Cancer AJCC v8||Drug: Bintrafusp Alfa Biological: Immunocytokine NHS-IL12 Radiation: Radiation Therapy||Phase 1|
I. To evaluate the safety and tolerability of bintrafusp alfa (M7824) in combination with immunocytokine NHS-IL12 (NHS-IL-12) and radiation therapy in patients with metastatic hormone receptor positive (HR+)/HER2- breast cancer.
II. To determine the recommended phase II dose (RP2D) of NHS-IL-12 in combination with M7824 and radiation therapy in patients with metastatic HR+/HER2- breast cancer.
I. To assess immunologic/molecular responses, specifically percent (%) change in tumor infiltrating lymphocytes (TIL) pre and post therapy to M7824 in combination with NHS-IL-12 and radiation therapy in patients with HR+/HER2- metastatic breast cancer.
II. To explore preliminary 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 M7824 in combination with NHS-IL-12 and radiation therapy.
I. To characterize circulating immune cell populations and cytokine profiles in tumor and circulation following treatment with M7824.
II. To conduct tissue-based ribonucleic acid sequencing (RNAseq), RNA scope, whole exome sequencing (WES) targeted sequencing.
III. To correlate dosimetry to response (assessed by degree of radiation fibrosis).
IV. To evaluate the pharmacokinetics of NHS-IL-12 in combination with M7824.
OUTLINE: This is a dose-escalation study of immunocytokine NHS-IL12.
Patients receive bintrafusp alfa intravenously (IV) over 1 hour on days 1 and 14 and immunocytokine NHS-IL12 subcutaneously (SC) on day 14. Beginning on day 14 of cycle 1, patients undergo radiation therapy once daily (QD) for up to 4 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||REINA: A Phase I Study of Radiation Enhanced IL 12-Necrosis Attraction in Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer Patients|
|Actual Study Start Date :||March 7, 2021|
|Estimated Primary Completion Date :||May 15, 2022|
|Estimated Study Completion Date :||May 15, 2022|
Experimental: Treatment (bintrafusp alfa, NHS-IL12, radiation therapy)
Patients receive bintrafusp alfa IV over 1 hour on days 1 and 14 and immunocytokine NHS-IL12 SC on day 14. Beginning on day 14 of cycle 1, patients undergo radiation therapy QD for up to 4 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Bintrafusp Alfa
Biological: Immunocytokine NHS-IL12
Radiation: Radiation Therapy
Undergo radiation therapy
- Incidence of adverse events (AEs) [ Time Frame: Up to 30 days post treatment ]Detailed information collected for each AE will include a description of the event, duration, severity, relationship to study treatment, action taken and clinical outcome. Severity of AEs will be grated according to Common Terminology Criteria for Adverse Events version .4.0.
- Recommended phase II dose (RP2D) [ Time Frame: Up to 28 days ]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.
- Progression-free survival (PFS) [ Time Frame: From start of treatment until objective tumor progression or death, whichever occurs first, assessed up to 1 year ]PFS will be estimated for all enrolled patients and patients who receive at least one treatment using Kaplan-Meier method and compared between or among patients' characteristic groups by log-rank test. Univariate Cox regression model may be applied to assess the effect of variables of interest on PFS when appropriate.
- Overall survival (OS) [ Time Frame: From treatment until death from any cause, assessed up to 1 year ]OS will be estimated for all enrolled patients and patients who receive at least one treatment using Kaplan-Meier method and compared between or among patients' characteristic groups by log-rank test. Univariate Cox regression model may be applied to assess the effect of variables of interest on OS, when appropriate.
- Percent (%) change in tumor infiltrating lymphocytes (TIL) [ Time Frame: Baseline up to 1 year ]The % change of TIL pre and post treatment will be estimated along with 95% confidence interval. Wilcoxon signed rank test may be used to examine whether the change in TIL is different from zero.
- Size of metastasis after treatment with both therapeutic agents with radiation (in-field) and nonirradiated (abscopal) sites [ Time Frame: Up to 1 years ]The difference in size of metastasis measured by the longest diameters of the tumor or the shortest diameter of a lymph node by Response Evaluation Criteria in Solid Tumors, before and after treatment will be estimated for both the irradiated site (diff irradiated) and the non-irradiated site (diff non-irradiated). Will also estimate the difference between the two different sites (diff = diff non-irradiated - diff irradiated). May evaluate if diff irradiated, diff non-irradiated, and diff = diff non-irradiated - diff Irradiated are significantly different from 0 by the Wilcoxon signed rank test.
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): NCT04756505
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Meghan Karuturi, MD 713-563-0714 firstname.lastname@example.org|
|Principal Investigator: Meghan Karuturi, MD|
|Principal Investigator:||Meghan Karuturi, MD||M.D. Anderson Cancer Center|