Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Neoplasm Metastasis

Breast Neoplasms

Disease Progression

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Reproductive Control Agents

Fulvestrant

Onapristone

Antineoplastic Agents, Hormonal

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

All participants will receive onapristone 50 mg p.o. BID (twice) daily and fulvestrant (500 mg) intramuscular injection on days 1, 15 (cycle 1), then two weeks later (cycle 2, day1), then once every 28 days thereafter. A cycle is defined as 28 days.

There will be no breaks between dosing cycles.

Onapristone is a type I antiprogestin which prevents the PgR from dimerizing and blocks ligand induced protein kinase-mediated phosphorylation of the PgR.

Fulvestrant binds, blocks and degrades the ER, completely inhibiting ER signaling.

Kari B Wisinski, MD

Sailaja Kamaraju, MD, MS

A phase II single-arm trial of onapristone in combination with fulvestrant for women and men with ER-positive, PgR-positive or negative and HER2-negative locally advanced or metastatic breast cancer after progression on aromatase and CDK4/6 inhibitors. The study will enroll up to 39 participants.

Onapristone and Fulvestrant for ER+ HER2- Metastatic Breast Cancer After Endocrine Therapy and CDK4/6 Inhibitors (The SMILE Study)

A Phase II Trial of OnapriStone in CoMbInation With FuLvestrant for Patients With ER-positive, and HER2-negative Metastatic Breast Cancer After Progression on Endocrine Therapy and CDK 4/6 Inhibitors

Best overall response of complete response (CR) or partial response (PR), as per RECIST 1.1. Point and 95% interval estimate of ORR will be evaluated accounting for possibility of early futility stopping.

Time from date of enrollment to the date of first documented disease progression or death due to any cause. PFS will be described with Kaplan-Meier (KM) Curve and its pointwise asymptotic 95% confidence bounds. Median PFS if reached will be extracted from this KM estimator.

Best overall response of CR, PR or stable disease (SD) lasting for ≥ 24 weeks, as per RECIST 1.1. DCR will be estimated with relative frequency and exact two-sided 95% binomial confidence interval.

Time from registration to first documented response (CR or PR) will be evaluated with a cumulative incidence where death will be as a competing risk to response.

Time between the first date of documented response to progression or death due to breast cancer. Duration of response will be assessed for a subgroup of subjects with observed response. The date of response will be denoted as time zero and time to progression or death will be evaluated with KM curve and 95% confidence interval (CI). Median time to response will be extracted from this KM curve.

Type, frequency and severity of adverse events and laboratory abnormalities (according to CTCAE version 5.0) will be summarized with descriptive frequency tables. See Adverse Events Section for detailed summary.

Context Therapeutics Inc.

University of Wisconsin, Madison

AEs may be spontaneously reported by the patient and/or in response to an open question from study personnel or revealed by observation, physical examination or other diagnostic procedures

All participants will receive onapristone 50 mg p.o. BID (twice) daily and fulvestrant (500 mg) intramuscular injection on days 1, 15 (cycle 1), then two weeks later (cycle 2, day1), then once every 28 days thereafter. A cycle is defined as 28 days.

There will be no breaks between dosing cycles.

Onapristone: Onapristone is a type I antiprogestin which prevents the PgR from dimerizing and blocks ligand induced protein kinase-mediated phosphorylation of the PgR.

Fulvestrant: Fulvestrant binds, blocks and degrades the ER, completely inhibiting ER signaling.

Onapristone In Combination With Fulvestrant

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Study was terminated early, sponsor closed study. Study not powered per protocol.

Number of Participants With Objective Response (ORR)

1 year PFS

17 month PFS

Number of Participants Experiencing Progression Free Survival (PFS)

Number of Participants With Disease Control (DCR)

Time to response could not be calculated as there was not a response to treatment within the study time points.

Time to Response

Duration of Response could not be calculated because there was no response to treatment within the study time points.

Spots Global Cancer Trial Database for Onapristone and Fulvestrant for ER+ HER2- Metastatic Breast Cancer After Endocrine Therapy and CDK4/6 Inhibitors (The SMILE Study)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial