Elacestrant + Onapristone for Advanced Breast Cancer

(ELONA Trial)

No longer recruiting at 2 trial locations

Overseen By Priya Marreddy

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Context Therapeutics Inc.

Must be taking: Goserelin, Triptorelin

Must not be taking: CYP3A4 inducers/inhibitors, Herbal meds

Disqualifiers: CNS metastases, Chemotherapy, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the effectiveness of combining two drugs, elacestrant (a type of hormone therapy) and onapristone, for treating advanced breast cancer that is hormone receptor-positive and HER2-negative. The researchers aim to determine if these drugs together can manage cancer in patients whose disease has spread beyond the breast. Individuals who have previously tried certain hormone therapies and have breast cancer testing positive for estrogen and progesterone receptors might be suitable candidates. Participants must also have at least one measurable cancerous area, and any brain metastases must be stable.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications before starting. Specifically, you must not take strong or moderate inducers or inhibitors of CYP3A4 within 14 days, herbal preparations within 7 days, and investigational anti-cancer therapy within 21 days before the trial. Please consult with the trial team for guidance on your specific medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that elacestrant, when used alone, usually causes manageable side effects. It tends to produce side effects similar to other hormone treatments, which many patients can handle without major issues. Onapristone, tested with other drugs, has been found safe, though some side effects may occur. When elacestrant and onapristone are used together, studies closely monitor any treatment-related side effects.

The current trial is in an early stage, so researchers are still gathering detailed safety information. However, testing these treatments together suggests some confidence in their potential safety. Always consult your doctor if considering joining a trial to understand any specific risks involved. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Elacestrant and Onapristone for advanced breast cancer because they offer a novel approach compared to current treatments like hormone therapies and chemotherapy. Elacestrant is a selective estrogen receptor degrader (SERD), which means it works by breaking down the estrogen receptors that fuel the growth of some breast cancers. Onapristone, on the other hand, is an anti-progestin that blocks progesterone, another hormone that can promote cancer growth. This combination targets the hormonal drivers of breast cancer more comprehensively, offering the potential for improved effectiveness, especially for patients who have become resistant to existing hormone therapies.

What evidence suggests that this treatment might be an effective treatment for advanced breast cancer?

Research shows that elacestrant may benefit patients with hormone receptor-positive metastatic breast cancer. For those whose cancer did not improve with previous treatments, elacestrant has proven beneficial. Studies indicate that elacestrant can significantly extend the time during which the cancer does not worsen, compared to standard treatments after other therapies have failed. In this trial, participants will receive a combination of elacestrant and onapristone. While researchers are still studying the combination, each drug has shown promising results on its own in similar cases. More research is needed to confirm their combined effectiveness, but early signs are encouraging. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with advanced ER+/PgR+/HER2- breast cancer who've had certain prior treatments. They must be able to take oral meds, have no uncontrolled gastrointestinal issues, and agree to contraception. Exclusions include treatment-naïve patients in the metastatic setting, recent major surgery, or active significant infections.

Inclusion Criteria

I have a tumor that can be measured and no recent brain issues.

My breast cancer is ER and PgR positive and HER2 negative, according to specific guidelines.

I am 18 or older and, if female, will take goserelin, or if male, will take triptorelin as required.

Exclusion Criteria

I am not using a highly effective birth control method.

I cannot take pills by mouth or have a condition affecting how my body absorbs food.

I have not had cancer besides my current one in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b Treatment

Open-label phase to determine the recommended Phase 2 dose (RP2D) of onapristone and elacestrant

9 months

Phase 2 Treatment

Evaluate the efficacy and safety of elacestrant in combination with onapristone in patients with ER+/PgR+/HER2- advanced/metastatic breast cancer

1.5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

21 months

What Are the Treatments Tested in This Trial?

Interventions

• Elacestrant
• Onapristone

Trial Overview The study tests elacestrant combined with onapristone in patients with a specific type of breast cancer that has spread. It's an early-to-mid stage trial assessing safety and effectiveness of this drug combo compared to existing treatments.

How Is the Trial Designed?

Group I: Elacestrant / Onapristone Experimental Treatment 2 Interventions

Elacestrant and Onapristone combination

Elacestrant is already approved in United States, European Union for the following indications:

Approved in United States as Orserdu for:

• ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer

Approved in European Union as Orserdu for:

• ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer

Who Is Running the Clinical Trial?

Context Therapeutics Inc.

Lead Sponsor

Trials

7

Recruited

260+

Published Research Related to This Trial

Elacestrant, a selective estrogen receptor degrader, was found to be safe and well tolerated in a study involving 140 postmenopausal women, with doses up to 1000 mg daily not reaching the maximum tolerated dose.

The drug showed good oral bioavailability and a half-life of 27 to 47 hours, allowing for once-daily dosing, while effectively engaging estrogen receptors and demonstrating some ability to cross the blood-brain barrier.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Studies of Elacestrant, A Novel Oral Selective Estrogen Receptor Degrader, in Healthy Post-Menopausal Women. Conlan, MG., de Vries, EFJ., Glaudemans, A., et al.[2021]

Elacestrant (RAD-1901) is a selective estrogen receptor degrader that was approved by the USFDA for treating ER+ HER2-positive breast cancer, demonstrating anticancer activity in both laboratory and animal models.

The review discusses Elacestrant's development, including its medicinal chemistry, mechanism of action, and safety profile based on clinical trial data, highlighting its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant: a new FDA-approved SERD for the treatment of breast cancer. Bhatia, N., Thareja, S.[2023]

Elacestrant, an oral selective estrogen receptor downregulator, was approved by the FDA in January 2023 for treating hormone receptor positive (HR+) HER2- advanced breast cancer, showing improved progression-free survival in patients with ESR1 mutations who had previously failed treatment with CDK 4/6 inhibitors and endocrine therapy.

Clinical trials indicate that elacestrant has a safety profile comparable to existing endocrine therapies and provides an effective alternative treatment option, especially for patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant for ER-Positive HER2-Negative Advanced Breast Cancer. Hageman, E., Lussier, ME.[2023]

Elacestrant was approved by the FDA for treating advanced or metastatic breast cancer in postmenopausal women and adult men with specific estrogen receptor mutations, highlighting its targeted approach for patients who have not responded to prior endocrine therapy.

The summary includes important details about elacestrant's mechanism of action and safety profile, which are crucial for understanding its role in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Approval of Elacestrant as a Selective Estrogen Receptor Degrader for the Treatment of Metastatic Breast Cancer. De, SK.[2023]

Elacestrant (ORSERDU™) is a newly approved oral medication for treating advanced or metastatic breast cancer in postmenopausal women and adult men with specific estrogen receptor mutations, following at least one line of endocrine therapy.

The drug specifically targets estrogen receptor-positive, HER2-negative breast cancer, and its approval in the USA marks a significant milestone in its development, with ongoing regulatory assessments in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant: First Approval. Hoy, SM.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11847623/

Elacestrant in hormone receptor-positive metastatic breast ... Elacestrant shows promise for improving outcomes in hormone receptor-positive metastatic breast cancer, but further research is needed to confirm its ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05618613?term=AREA%5BInterventionSearch%5D(rad1901)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=7

Study of Elacestrant in Combination With Onapristone ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

3. cancertherapyadvisor.com cancertherapyadvisor.com/news/breast-cancer-elacestrant-onapristone-hr-positive-her2-negative-advanced/

Clinical Trial: Elacestrant Plus Onapristone in HR+, HER2 Researchers are conducting a phase 1b/2 study to test elacestrant plus onapristone in patients with HR+, HER2- advanced breast cancer.

4. cancernetwork.com cancernetwork.com/view/20-tip-elona-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

20 TIP ELONA: An Open-Label, Phase 1b-2 Study of ... Elacestrant showed a statistically significant improvement in PFS when compared to standard-of-care endocrine therapy after progression on CDK4/6 inhibitors.

5. withpower.com withpower.com/trial/elacestrant-onapristone-for-advanced-breast-cancer-164a8

Elacestrant + Onapristone for Advanced Breast Cancer Elacestrant is a new drug that has shown effectiveness in patients with breast cancer that has not responded to previous treatments.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06938711

A Rollover Protocol of Elacestrant, in Combination With ... Characterize the safety of elacestrant in combination with onapristone. Monitor the treatment-related adverse events as assessed by CTCAE v4.0, 7 months ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10667141/

Elacestrant: First Approval - PMC - PubMed Central Monotherapy with oral elacestrant exhibited a manageable safety profile consistent with other endocrine treatments in postmenopausal women and ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05618613

NCT05618613 | Study of Elacestrant in Combination With ... This is a multicenter, Phase 1b-2 study of elacestrant in combination with onapristone in patients with advanced/metastatic ER+/PgR+/HER2- breast cancer.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1526820924003331

A Phase II Trial of Onapristone and Fulvestrant for Patients ... The SMILE study is a multi-institutional phase II clinical trial to determine the efficacy and safety of an antiprogestin, onapristone, in combination with ...