Ignite Creation Date:
2025-12-25 @ 3:32 AM
Ignite Modification Date:
2025-12-26 @ 2:14 AM
Study NCT ID:
NCT04756505
Status:
WITHDRAWN
Last Update Posted:
2023-12-27
First Post:
2021-02-11
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Immunotherapy (NHS-IL12 & Bintrafusp Alfa) and Radiation Therapy for the Treatment of Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer, the REINA Trial
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
REINA: A Phase I Study of Radiation Enhanced IL 12-Necrosis Attraction in Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer Patients
Status:
WITHDRAWN
Status Verified Date:
2023-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Per Sponsor Request-no longer manufacturing the study drug
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial is to find out the best dose, possible benefits and/or side effects of NHS-IL12 given together with bintrafusp alfa and radiation therapy in treating patients with hormone receptor positive, HER2 negative breast cancer that has spread to other places in the body (metastatic). Immunotherapy with NHS-IL12, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Immunotherapy with bintrafusp alfa, a bifunctional fusion protein composed of the monoclonal antibody avelumab and TGF-beta, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving NHS-IL12, bintrafusp alfa, and radiation therapy may kill more tumor cells.
Detailed Description:
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
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.
EXPLORATORY OBJECTIVES:
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.
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.
SECONDARY OBJECTIVES:
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.
EXPLORATORY OBJECTIVES:
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 Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: