Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Carcinoma

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Hormones

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

Symptoms and General Pathology

Rare Diseases

Recurrence

Triple Negative Breast Neoplasms

Inflammatory Breast Neoplasms

Inflammatory Breast Cancer

Antirheumatic Agents

Micronutrients

Hematinics

Vitamins

Vaccines

Cyclophosphamide

Molgramostim

Sargramostim

Folic Acid

Vitamin B Complex

Adjuvants, Vaccine

Immunologic Factors

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Folinic Acid

Folate

Vitamin B9

Patients receive cyclophosphamide PO BID on days 1-7 and 15-21 of cycle 1 only. Starting cycle 2, patients receive multi-epitope folate receptor alpha peptide vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for cycles 2-7 and every 6 months for cycles 8-14 in the absence of disease progression or unacceptable toxicity.

Patients receive cyclophosphamide as in Arm I. Starting cycle 2, patients receive placebo vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for cycles 2-7 and every 6 months for cycles 8-14 in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Multi-epitope Folate Receptor Alpha Peptide Vaccine

Placebo Administration

Kathryn J Ruddy

This randomized phase II trial studies how well multi-epitope folate receptor alpha peptide vaccine, sargramostim (GM-CSF), and cyclophosphamide work to prevent the recurrence of stage 1-3 triple negative breast cancer. Vaccines made from a person's white blood cells mixed with tumor proteins may help the body build an effective immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving multi-epitope folate receptor alpha peptide vaccine, sargramostim (GM-CSF), and cyclophosphamide may work well together to prevent cancer recurrence after surgery and other standard treatments for triple negative breast cancer.

PRIMARY OBJECTIVE:

I. To show that multi-epitope folate receptor alpha peptide vaccine (folate receptor \[FR\]alpha peptide vaccine) with sargramostim (GM-CSF) adjuvant will prolong the disease-free survival (DFS) compared to GM-CSF adjuvant treatment in patients with triple negative breast cancer.

SECONDARY OBJECTIVE:

I. To compare the safety and tolerability of metronomic cyclophosphamide followed by FRalpha peptide vaccine with GM-CSF versus GM-CSF alone.

CORRELATIVE RESEARCH OBJECTIVES:

I. To determine whether high level of antibody and cellular immune response toward the FRalpha measured at baseline is a prognostic factor for vaccine immune response and/or cancer relapse.

II. To determine whether the level of tumor expression of FRalpha at baseline is a prognosis factor for vaccine immune response and/or cancer relapse.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive cyclophosphamide orally (PO) twice daily (BID) on days 1-7 and 15-21 of cycle 1 only. Starting cycle 2, patients receive multi-epitope folate receptor alpha peptide vaccine with sargramostim intradermally (ID) on day 1. Treatment repeats every 28 days for cycles 2-7 and every 6 months for cycles 8-14 in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive cyclophosphamide as in Arm I. Starting cycle 2, patients receive placebo vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for cycles 2-7 and every 6 months for cycles 8-14 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 3 years.

Multi-epitope Folate Receptor Alpha Peptide Vaccine, GM-CSF, and Cyclophosphamide in Treating Patients With Triple Negative Breast Cancer

Double Blind, Parallel Groups, Controlled, Randomized Phase II Trial to Evaluate Vaccination With Folate Receptor Alpha Peptide Vaccine With GM-CSF as Vaccine Adjuvant Following Oral Cyclophosphamide Versus GM-CSF/Placebo to Prevent Recurrence in Patients With Triple Negative Breast Cancer

Will be estimated using the method of Kaplan-Meier. Will use the stratified log-rank tests.

The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed by primary disease site to determine toxicity patterns. Will use the Cochran-Mantel Haenszel chi-squared test with study stratification factors. Will use logistic regression to test differences in proportions while controlling for the known covariates.

Will be determined along with its corresponding 95% confidence interval.

FRalpha levels at baseline will be examined as a prognostic factor in the vaccine immune response. A multivariable Cox proportional hazard model will be used to assess baseline FRalpha levels as a potential prognostic factor for immune response.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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
Multi-epitope Folate Receptor Alpha Peptide Vaccine, GM-CSF, and Cyclophosphamide in Treating Patients With Triple Negative Breast Cancer	NCT03012100	Bilateral Breas... Breast Inflamma... Stage IB Breast... Stage II Breast... Stage IIA Breas... Stage IIB Breas... Stage III Breas... Stage IIIA Brea... Stage IIIB Brea... Stage IIIC Brea... Triple-Negative... Unilateral Brea...	Cyclophosphamid... Laboratory Biom... Multi-epitope F... Placebo Adminis... Sargramostim	18 Years -	Academic and Community Cancer Research United

Spots Global Cancer Trial Database for unilateral breast carcinoma