Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Carcinoma

Breast Neoplasms

Adenocarcinoma

Necrosis

Breast Diseases

Skin Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Hormones

Immunomodulating Agents

Interleukin-12

Antibodies

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Adjuvants, Immunologic

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

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.

Bintrafusp Alfa

Immunocytokine NHS-IL12

Radiation Therapy

Meghan Karuturi, MD

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.

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.

Immunotherapy (NHS-IL12 & Bintrafusp Alfa) and Radiation Therapy for the Treatment of Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer, the REINA Trial

REINA: A Phase I Study of Radiation Enhanced IL 12-Necrosis Attraction in Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer Patients

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.

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.

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.

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.

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.

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.

M.D. Anderson Cancer Center

Niraparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Patients receive abemaciclib PO BID and niraparib PO QD. Treatment repeats every 28 days for up to 2-4 cycles in the absence of disease progression or unacceptable toxicity. Patients who complete 4 cycles undergo standard of care mastectomy or lumpectomy. Patients demonstrating progressive disease after only 2 cycles are switched to receive standard of care chemotherapy prior to undergoing mastectomy or lumpectomy.

Abemaciclib

Niraparib Tosylate Monohydrate

Alexandra Zimmer, M.D.

This phase I trial tests the side effects and best dose of abemaciclib and niraparib in treating patients with breast cancer that is positive for estrogen or progesterone receptors (hormone receptor positive \[HR+\]) and HER2 negative. Abemaciclib may stop the growth of tumor cells by blocking certain proteins called cyclin-dependent kinases, which are needed for cell growth. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as niraparib, can keep PARP from working so tumor cells can't repair themselves and grow. Giving abemaciclib and niraparib together before surgery may make the tumor smaller.

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose (MTD) and/or recommended phase 2 dose of the combination of abemaciclib and niraparib tosylate monohydrate (niraparib).

II. To assess safety and tolerability of the combination of abemaciclib and niraparib in early stage HR+ breast cancer.

SECONDARY OBJECTIVES:

I. To determine clinical response to treatment. II. To determine pathologic response to treatment. III. To determine feasibility of combination as determined by no delay to standard of care breast surgery.

EXPLORATORY OBJECTIVE:

I. To assess occurrence of secondary myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) malignancy.

OUTLINE: This is a phase 1 dose-escalation study of abemaciclib in combination with niraparib followed by a dose-expansion study.

Patients receive abemaciclib orally (PO) twice daily (BID) and niraparib PO once daily (QD). Treatment repeats every 28 days for up to 2-4 cycles in the absence of disease progression or unacceptable toxicity. Patients who complete 4 cycles undergo standard of care mastectomy or lumpectomy. Patients demonstrating progressive disease after only 2 cycles are switched to receive standard of care chemotherapy prior to undergoing mastectomy or lumpectomy.

Patients are followed up at 30 days after date of surgery, every 3 months for the first 6 months, every 6 months for 2 years, then annually for up to 5 years from date of surgery.

Abemaciclib and Niraparib Before Surgery for the Treatment of Hormone Receptor Positive HER2 Negative Breast Cancer

A Phase 1 Study of Abemaciclib and Niraparib as Neoadjuvant Therapy in Hormone Receptor Positive (HR+) HER2 Negative (HER2-) Breast Cancer

Dose-limiting toxicities will specifically be reported for the DLT evaluation period using the MTD-evaluable population.

Adverse events will be tabulated by the Medical Dictionary for Regulatory Activities (MedDRA version 21.1) preferred term and system organ class and a preferred term. The severity of the AEs will be assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Descriptive statistics using the safety evaluable population will be used to report on all on-study AEs, grade 3-4 AEs, treatment-related AEs, grade 3-4 treatment-related AEs, serious adverse events (SAEs), treatment-related SAEs, and AEs leading to discontinuation per CTCAE v5.0. Grade 3-4 laboratory abnormalities will be summarized using worst grade NCI CTCAE v 5.0 criteria.

Overall response will be summarized descriptively. ORR will be estimated with 95% confidence interval (CI). The CI will be calculated based on the exact method for binomial distributions.

An estimate of CBR will be measured and reported with 95% exact CI. Participants who achieve a complete response (CR), partial response (PR), or stable disease (SD) for at least 6 months on the current protocol will be qualified as deriving benefit from therapy and will count towards the CBR measurement.

pCR will be tabulated as proportions and analyzed descriptively. Rate of delay to breast surgery will be summarized descriptively

RCB will be tabulated as proportions and analyzed descriptively. Rate of delay to breast surgery will be summarized descriptively

Defined as proportion of participants with time-to-surgery \> 90 days following completion of study therapy due to study-treatment related toxicity.

Eli Lilly and Company

GlaxoSmithKline

Oregon Health and Science University

OHSU Knight Cancer Institute

Principal Investigator

Patients complete a series of questionnaires over 15 minutes about knee function and pain, as well as physical activity. Patients also undergo an MRI over 60 minutes.

Magnetic Resonance Imaging

Questionnaire Administration

Roland Krug, PhD

This study investigates the impact of breast cancer treatment on joint health, cartilage, composition, and bone structure in the knee and hand in patients with hormone-receptor positive stage I-III breast cancer and healthy patients. The investigators will use Magnetic Resonance Imaging (MRI) to assess the quality of hand and knee joints. This study may help doctors learn more about hand and knee joint pain that occurs during aromatase inhibitor treatment.

PRIMARY OBJECTIVE:

I. To investigate pathological alterations in cartilage and joints in breast cancer patients on aromatase inhibitor (AI)s with and without pain and in healthy control patients.

OUTLINE:

Patients complete a series of questionnaires over 15 minutes about knee function and pain, as well as physical activity. Patients also undergo an MRI of about 60 minutes.

After completion of study, a subset of patients are followed up at 6 months.

Impact of Breast Cancer Treatment on Joint Health, Cartilage Composition, and Bone Structure in the Knee and Hand

Will determine differences in hyaline cartilage biochemical composition (using magnetic resonance imaging) between breast cancer patients under aromatase inhibitor (AI) treatment. Linear regression models will be used to assess differences in joint parameters outcomes between healthy controls, AI patients with pain, and AI patients without pain (predictors).

Will determine differences in morphological joint abnormalities (using semi-quantitative magnetic resonance-based scores) between breast cancer patients under aromatase inhibitor (AI) treatment. Linear regression models will be used to assess differences in joint parameters outcomes between healthy controls, AI patients with pain, and AI patients without pain (predictors).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Immunotherapy (NHS-IL12 & Bintrafusp Alfa) and Radiation Therapy for the Treatment of Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer, the REINA Trial	NCT04756505	Anatomic Stage ... Hormone Recepto... Metastatic Brea... Metastatic HER2... Prognostic Stag...	Bintrafusp Alfa Immunocytokine ... Radiation Thera...	18 Years -	M.D. Anderson Cancer Center
Abemaciclib and Niraparib Before Surgery for the Treatment of Hormone Receptor Positive HER2 Negative Breast Cancer	NCT04481113	Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... HER2 Negative B... Hormone Recepto... Invasive Breast... Multifocal Brea... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Unilateral Brea...	Abemaciclib Niraparib Tosyl...	18 Years -	OHSU Knight Cancer Institute
Impact of Breast Cancer Treatment on Joint Health, Cartilage Composition, and Bone Structure in the Knee and Hand	NCT04876378	Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Hormone Recepto... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag...	Magnetic Resona... Questionnaire A...	- 70 Years	University of California, San Francisco
Immunotherapy (NHS-IL12 & Bintrafusp Alfa) and Radiation Therapy for the Treatment of Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer, the REINA Trial	NCT04756505	Anatomic Stage ... Hormone Recepto... Metastatic Brea... Metastatic HER2... Prognostic Stag...	Bintrafusp Alfa Immunocytokine ... Radiation Thera...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for hormone receptor positive breast adenocarcinoma