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Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Reproductive Control Agents

Estrogens

Progesterone

Onapristone

Hormones

Hormone Antagonists

Elacestrant 200mg, 300mg, or 400mg once daily oral dosing in cycles of 28 days.

Elacestrant

Onapristone 40mg or 50mg twice daily oral dosing in cycles of 28 days.

This is a multicenter, Phase 1b-2 study of elacestrant in combination with onapristone in patients with advanced/metastatic ER+/PgR+/HER2- breast cancer.

This is a multicenter, phase 1b-2 trial. The phase 1b part of the trial is open label and aims to determine the recommended Phase 2 dose (RP2D) of onapristone and elacestrant when administered together. The Phase 2 part of the trial will evaluate the efficacy and safety of this combination in patients with ER+/PgR+/HER2- advanced/metastatic breast cancer after prior therapy with a CDK4/6 inhibitor.

Study of Elacestrant in Combination With Onapristone in Patients With Advanced or Metastatic Breast Cancer

An Open-Label, Phase 1b-2 Study of Elacestrant, in Combination With Onapristone in Patients With Estrogen Receptor-Positive, Progesterone Receptor-Positive, HER2-negative Advanced or Metastatic Breast Cancer (ELONA)

Proportion of patients achieving a best overall response of confirmed partial or complete response (PR+CR).

Characterize the AEs of elacestrant in combination with onapristone.

Characterize the serious adverse events (SAEs) of elacestrant in combination with onapristone.

Characterize the safety in terms of changes in clinical laboratory values of elacestrant in combination with onapristone.

Characterize the safety in terms of changes in vital sign measurements of elacestrant in combination with onapristone.

Characterize the safety in terms of changes in ECG parameters of elacestrant in combination with onapristone.

Evaluate the area under the plasma concentration-time curve over the dosing interval of elacestrant as well as onapristone and their metabolites (Phase 1).

Evaluate the maximum plasma concentration (Cmax) of elacestrant as well as onapristone and their metabolites (Phase 1).

Evaluate the time of the maximum observed plasma concentration (Tmax) of elacestrant as well as onapristone and their metabolites (Phase 1).

Evaluate the trough concentration of elacestrant as well as onapristone and their metabolites (Phase 1).

Time from the date of the first documented CR/PR until first documentation of disease progression or death, whichever comes first.

Proportion of subjects achieving a best overall or complete response, or durable stable disease (duration is at least 23 weeks).

Time from the date of the first dose to the date of the first documentation of disease progression or death, whichever occurs first.

Time from first dose date to the date of death from any cause.

Context Therapeutics Inc.

Letrozole

Palbociclib

Aromatase Inhibitors

Enzyme Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Protein Kinase Inhibitors

This study has two stages: a dose-finding stage and a dose expansion stage. Stage 1 of the study will utilize a standard 3+3 dose de-escalation design with a total of three dose levels of onapristone ER, 30mg PO BID, 40mg PO BID, and 50mg PO BID given on a 28-day cycle. Onapristone ER will be given in addition to letrozole 2.5mg QD and each patient's pre-enrollment dose of palbociclib.

Letrozole will be given daily on days 1-28.

Palbociclib will be given daily on days 1-21 and held on days 22-28, as per standard FDA-approved dosing guidelines.

Onapristone will be given daily on days 1-28.

Onapristone ER

Komal Jhaveri, MD

The researchers are doing this study to find out whether the study drug onapristone ER, combined with the standard treatment for your cancer (letrozole and palbociclib), is a safe treatment for people who have metastatic or unresectable ER+/PR+/HER2- breast cancer. The researchers will test different doses of the study drug to find the highest dose that causes few or mild side effects.

This is an open label, single institution pilot phase 1b study of the oral progesterone antagonist, onapristone ER (Apristor), used as triplet escalation therapy patients with ER+/PR+/HER2- MBC who do not achieve mCR after six months (+/- 4 weeks) of treatment with letrozole and palbociclib in the first line.

A Study of Letrozole, Palbociclib, and Onapristone ER in People With Metastatic Breast Cancer

ctDNA-guided Adaptive Therapy Escalation in ER+ MBC: A Phase 1b Study With Letrozole, Palbociclib and Onapristone ER

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

The RP2D/MTD will be defined as the dose level at which a dose limiting toxicity (DLT) occurs in at most 1 out of 6 patients in that dose cohort.

Memorial Sloan Kettering Cancer Center

Symptoms and General Pathology

Neoplasm Metastasis

Disease Progression

Fulvestrant

Antineoplastic Agents, Hormonal

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.

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.

Duration of Response

Participants Experiencing Grade 1 Adverse Events

Participants Experiencing Grade 2 Adverse Events

Participants Experiencing Grade 3 Adverse Events

Incidence of Treatment-Related Adverse Events

Overall Study

50 mg given orally (PO), twice a day (BID), in a continuous schedule (QD). 3 weeks of (+/-3 days) of ONA treatment

50 mg given orally (PO), twice a day (BID), in a continuous schedule (QD) during 3 weeks (+/-3 days)

ONAWA is a window of opportunity, prospective, multicenter, phase 0 trial which evaluates the effect of onapristone (ONA) on proliferation after 3 weeks of treatment in postmenopausal women with ER+/PgR+ and HER2-negative early breast cancer amenable to pre-operative endocrine therapy and surgery.

The main hypothesis is that onapristone, an antiprogestin will induce a significant proliferative arrest in HR+/HER2-negative breast cancer. The primary endpoint is chosen based on reports which related the 2.7% Ki67 value (natural log of 1) both after a 15 days1 or 3-4 months of neoadjuvant endocrine treatment with favorable breast cancer relapse free and overall survival2,3. Hence, this Ki67 cut-off (Complete Cell Cycle Arrest, or CCCA) has been consistently used in recent trials as an acceptable surrogate marker of clinical and biological efficacy, even though the achievement of a pathological complete response is very unusual in luminal tumors after preoperative endocrine therapy. Trials with biological endpoint, including the so-called window of opportunity trials such as the ONAWA study provide tumor tissue before and after a short course of a given therapy for biomarker analyses of response and resistance. The aim of these studies is to improve the investigator's understanding regarding the biologic effect of a given drug, in order to better define its target population early in its development without interfering with the standard treatment pattern of the patient.

window of opportunity, prospective, multicenter, phase 0 trial

Onapristone as Preoperative Treatment for Postmenopausal Women With Hormone Receptor + and HER2- Breast Cancer

A Window of Opportunity Trial of Onapristone as Preoperative Treatment for Postmenopausal Women With Hormone Receptor-Positive and HER2-negative Breast Cancer

IHC of tumor expression of ER, PgR, CD24, CD44, ALDH1, Ser294-PgR, Ki67

Suppression of PAM50 11-gene proliferation signature according to PAM50 subtypes upon treatment.. These changes will be analyzed according to the formula: Mean suppression = 100 - \[geometric mean (post-treatment / pretreatment · 100)\].

mean suppression of PAM50 11-gene proliferation signature according to PAM50 subtypes

* expression of 770 genes across of 23 categories of BC tumor biology
* changes in the expression of the 16-PgR target genes

* Development of a gene signature of response to ONA based on changes in the expression of 770 genes by the nCounter Breast 360TM panel in the tumor.
* Analysis of the presence of ctDNA and its dynamics after ONA treatment.

Incidence, duration and severity of Adverse Events (AEs) assessed by the NCI Common Terminology for Classification of Adverse Events (CTCAE) version 5.0, including treatment discontinuations.

SOLTI Breast Cancer Research Group

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Sarcoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

Soft Tissue Sarcoma

Uterine Sarcoma

onapristone 10 mg BID extended-release tablets

onapristone 20 mg BID extended-release tablets

onapristone 30 mg BID extended-release tablets

onapristone 40 mg BID mg extended-release tablets

onapristone 50 mg BID extended-release tablets

onapristone 100 mg QD immediate-release tablets

onapristone

Alice S Bexon, MD

Jacques Bonneterre, MD

Paul H Cottu, MD

Andrea Varga, MD

This is a multi-center, open-label, randomized, parallel group two-stage phase 1 study with a phase 2 expansion component in pts with recurrent or metastatic APRpos uterine endometrioid adenocarcinoma. Stage 1: Six dose cohorts, 5 using the extended release tablet (ER) formulation (10 mg BID, 20 mg BID, 30 mg BID, 40 mg BID, 50 mg BID) and 1 using the immediate-release (IR) tablet formulation 100 mg QD will be randomized in parallel. After enrollment of 36 patients in Stage 1, a dose of 50 mg BID was determined to be the RP2D. Stage 2: An additional 10 patients with recurrent or metastatic APRpos uterine endometrioid adenocarcinoma (Stage 2a) will be enrolled at the RP2D. Based on the response in Stage 2a, the cohort will be further expanded by up to 19 more patients to a total of 29 patients to confirm the efficacy and safety profile of onapristone in this selected patient population (Stage 2b).

Phase 1-2 Study of Onapristone in Patients With Progesterone Receptor Expressing Cancers

Safety will be assessed by physical exam, vital signs, monitoring of adverse events, changes in ECG, and other clinical laboratory values

Arno Therapeutics

Prostatic Neoplasms

Recurrence

Urogenital Neoplasms

Genital Diseases

Prostatic Diseases

Genital Diseases, Male

Genital Neoplasms, Male

Urogenital Diseases

Male Urogenital Diseases

onapristone 40 mg BID extended-release tablets

Expansion cohort: onapristone 30 mg BID + abiraterone 1000 mg

Expansion cohort: onapristone 50 mg BID + abiraterone 1000 mg

abiraterone

Gerhardt Attard, MD, PhD, MRCP

Johann S De Bono, MD, PhD, MSc, FRCP

Joaquin Mateo, MD

This is an open-label, randomized, parallel group two-stage phase 1-2 study with an escalation and an expansion component. This study will evaluate an extended-release (ER) formulation of onapristone in patients with prostate cancer in which Progesterone Receptor (PR) may be contributing to tumor progression. A companion diagnostic to select patients whose prostate cancer expresses the activated form of the PR (APR) is under development and will be implemented in this study; it may be used to further enrich the selection of the population based upon ongoing review of the results. Patients will be treated until occurrence of an intolerable safety issue, treatment failure, if patient elects to withdraw, or for non-compliance with either protocol-specified evaluations or onapristone treatment. An additional cohort of patients will be included at the recommended phase 2 dose to gain additional understanding of the onapristone safety profile and potential anti-cancer activity.

Phase 1-2 Study of Onapristone in Patients With Advanced Castration-resistant Prostate Cancer

A Phase 1-2 Study of Onapristone in Patients With Advanced Castration-resistant Prostate Cancer

* Objective partial or complete response by RECIST 1.1, confirmed on a second CT scan at least 4 weeks apart and / or
* PSA decline of ≥ 50% (according to the PCWG2).

Safety will be assessed by physical exam, vital signs, monitoring of adverse events, changes in ECG, and changes in PSA and other clinical laboratory values.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Elacestrant in Combination With Onapristone in Patients With Advanced or Metastatic Breast Cancer	NCT05618613	Breast Cancer	Elacestrant Onapristone	18 Years -	Context Therapeutics Inc.
A Study of Letrozole, Palbociclib, and Onapristone ER in People With Metastatic Breast Cancer	NCT04872608	Metastatic Brea... Unresectable Br...	Letrozole Palbociclib Onapristone ER	18 Years -	Memorial Sloan Kettering Cancer Center
Onapristone and Fulvestrant for ER+ HER2- Metastatic Breast Cancer After Endocrine Therapy and CDK4/6 Inhibitors (The SMILE Study)	NCT04738292	ER-positive Bre... HER2-negative B... Metastatic Canc...	Onapristone Fulvestrant	18 Years -	University of Wisconsin, Madison
Onapristone as Preoperative Treatment for Postmenopausal Women With Hormone Receptor + and HER2- Breast Cancer	NCT04142892	Breast Cancer	Onapristone	18 Years -	SOLTI Breast Cancer Research Group
Onapristone and Fulvestrant for ER+ HER2- Metastatic Breast Cancer After Endocrine Therapy and CDK4/6 Inhibitors (The SMILE Study)	NCT04738292	ER-positive Bre... HER2-negative B... Metastatic Canc...	Onapristone Fulvestrant	18 Years -	University of Wisconsin, Madison
Phase 1-2 Study of Onapristone in Patients With Progesterone Receptor Expressing Cancers	NCT02052128	Progesterone Re...	onapristone	18 Years -	Arno Therapeutics
Onapristone as Preoperative Treatment for Postmenopausal Women With Hormone Receptor + and HER2- Breast Cancer	NCT04142892	Breast Cancer	Onapristone	18 Years -	SOLTI Breast Cancer Research Group
Study of Elacestrant in Combination With Onapristone in Patients With Advanced or Metastatic Breast Cancer	NCT05618613	Breast Cancer	Elacestrant Onapristone	18 Years -	Context Therapeutics Inc.
Phase 1-2 Study of Onapristone in Patients With Advanced Castration-resistant Prostate Cancer	NCT02049190	Prostate Cancer Metastatic Pros... Androgen-indepe... Recurrent Prost...	onapristone abiraterone	18 Years -	Arno Therapeutics

Spots Global Cancer Trial Database for onapristone

Every month we try and update this database with for onapristone cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for onapristone

Every month we try and update this database with for onapristone cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for onapristone cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.