Onapristone + Anastrozole for Endometrial Cancer

Not currently recruiting at 2 trial locations

Overseen By Russell J Schilder, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Thomas Jefferson University

Must be taking: Onapristone, Anastrozole

Must not be taking: Hormonal therapy

Disqualifiers: Concurrent malignancy, Brain metastasis, Cardiac disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining two drugs, onapristone and anastrozole, can more effectively treat hormone receptor-positive endometrial cancer that hasn't responded to previous treatments. Onapristone (extended-release) blocks progesterone, while anastrozole reduces estrogen production; both hormones can fuel cancer growth. The trial aims to determine if this combination works better than anastrozole alone. Suitable participants have endometrial cancer that persists despite platinum/taxane chemotherapy and must be postmenopausal (not having periods for 12 months if over 55 or having had a specific surgery). As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot have taken certain hormonal therapies in the past 2 months or any prescription medications that interfere with onapristone in the 28 days before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that onapristone, in its extended-release form, is generally well-tolerated. Some studies suggest this version might lower the risk of liver problems, enhancing safety. However, one study found it didn't consistently reduce tumor size.

Anastrozole is a well-known treatment with a good safety record, often used for hormone-related cancers. One study found that anastrozole reduced the risk of developing endometrial cancer compared to no treatment.

Overall, both treatments appear generally safe based on current research. While they are usually safe, side effects may occur. Prospective trial participants should consult their doctors to understand the risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for endometrial cancer?

Researchers are excited about the combination of onapristone and anastrozole for endometrial cancer because it offers a novel approach to treatment. Unlike traditional therapies that often focus on chemotherapy or surgery, onapristone is a progesterone receptor antagonist that specifically targets hormone pathways involved in cancer growth. When combined with anastrozole, an aromatase inhibitor that reduces estrogen levels, this treatment aims to more effectively halt tumor progression. This dual-action approach could potentially provide better outcomes for patients by addressing the hormonal drivers of the disease more comprehensively.

What evidence suggests that onapristone and anastrozole might be an effective treatment for endometrial cancer?

Research has shown that combining onapristone with anastrozole might be more effective than using anastrozole alone for treating a type of endometrial cancer that relies on hormones to grow. In this trial, participants will receive both onapristone and anastrozole. Onapristone blocks progesterone, a hormone that can aid cancer cell growth. Anastrozole reduces estrogen levels in the body, which also contributes to cancer growth. Previous studies found that this combination can stabilize the disease in some patients, with benefits lasting at least 24 weeks for some. This suggests the combination could be promising for those whose cancer hasn't responded to other treatments. ^{6 7 8 9 10}

Who Is on the Research Team?

Tommy Buchanan, MD

Principal Investigator

Thomas Jefferson University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with hormone receptor positive endometrial cancer that hasn't improved after platinum/taxane chemotherapy. Participants must have tried no more than two treatments, be able to swallow pills, weigh over 30 kg, and have recovered from previous therapies. Women must be postmenopausal and not pregnant or nursing. People with certain heart conditions, untreated brain metastases, severe infections or recent major surgery are excluded.

Inclusion Criteria

I am fully active or can carry out light work.

I am a woman who has gone through menopause.

I have fully recovered from my previous radiation treatments.

Exclusion Criteria

I have had cancer treatment, including trial drugs, within the last 3 weeks.

I haven't had chemotherapy, radiotherapy, immunotherapy, or major surgery in the last 3 weeks.

I haven't taken any medication in the last 28 days that could affect my treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive onapristone orally twice daily and anastrozole once daily on days 1-28, repeated every 28 days for up to 24 cycles

24 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

12 months

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Anastrozole
• Extended-release Onapristone

Trial Overview The trial tests onapristone combined with anastrozole against refractory hormone receptor positive endometrial cancer. Onapristone blocks progesterone use by tumor cells while anastrozole inhibits estrogen production in the body. The goal is to see if this combination works better than anastrozole alone.

How Is the Trial Designed?

Group I: Treatment (onapristone, anastrozole) Experimental Treatment 6 Interventions

Patients receive onapristone PO BID and anastrozole PO QD on days 1-28. Treatment repeats every 28 days for up to 24 cycles (24 months) until November 30, 2023 or in the absence of disease progression or unacceptable toxicity.

Anastrozole is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Approved in Japan as Arimidex for:

• Breast cancer

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

Context Therapeutics Inc.

Industry Sponsor

Trials

7

Recruited

260+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Anastrozole, a selective aromatase inhibitor, was evaluated in a phase II trial involving 53 women with recurrent müllerian cancer, showing modest toxicity and primarily resulting in stable disease rather than significant tumor shrinkage.

While 42% of patients experienced stable disease for over 90 days, the overall tumoricidal activity was minimal, indicating that anastrozole may not be effective as a primary treatment for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of anastrozole in women with asymptomatic müllerian cancer. del Carmen, MG., Fuller, AF., Matulonis, U., et al.[2019]

In a retrospective analysis of the ATAC trial, women taking tamoxifen experienced significantly more gynecologic adverse events (34.2%) compared to those taking anastrozole (20.5%), leading to more medical interventions, including a nearly fourfold increase in hysterectomies.

The findings support the use of anastrozole as the preferred initial treatment for early hormone receptor-positive breast cancer due to its lower incidence of gynecologic complications, particularly since most adverse events with tamoxifen occurred within the first 2.5 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A lower incidence of gynecologic adverse events and interventions with anastrozole than with tamoxifen in the ATAC trial. Duffy, SR., Distler, W., Howell, A., et al.[2018]

In a study of 6241 postmenopausal women with early-stage breast cancer, anastrozole was found to have significantly fewer treatment-related adverse events compared to tamoxifen, indicating better tolerability.

Anastrozole also demonstrated a more favorable risk-benefit profile, with lower rates of serious adverse events and recurrence compared to tamoxifen, making it a preferable option for adjuvant treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Buzdar, A., Howell, A., Cuzick, J., et al.[2022]

Citations

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OATH trial: A phase II clinical trial evaluating the ... A sample size of 25 pts will achieve 80% power to detect an improvement in 4-month PFS estimates from 25% (historical) to 52% and an improvement ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04719273

Onapristone and Anastrozole for the Treatment of ... Giving onapristone with anastrozole may work better than anastrozole alone in treating patients with hormone receptor positive endometrial cancer. Detailed ...

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Basket study of oral progesterone antagonist onapristone ... [27] In this phase I study, 9 of 52 patients had clinical benefit lasting at least 24 weeks, and 11 patients experienced stable disease as best ...

4. onclive.com onclive.com/view/ona-xr-anastrozole-combo-delivers-promising-early-results-in-hr-metastatic-endometrial-cancer

ONA-XR/Anastrozole Combo Delivers Promising Early ... In KEYNOTE-775, the 4-month PFS rate was 67% for the lenvatinib/pembrolizumab combination and 42% for chemotherapy. The ORR was 32% and 14%, ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1048891X24000318

Basket study of oral progesterone antagonist onapristone ... All 14 patients were evaluable, with median progression-free survival of 3.6 months (range; 1.7-7.1), a 6-month progression-free survival rate of 28.6% (range; ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24050151

372 Endometrial Cancer Data From The Atac ('Arimidex', ... Conversely, the observed EC rates were lower than expected for anastrozole in all regions. EC risk was reduced by 41% in North America (SIR 0.59; 95% CI 0.02, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2690973/

Long-term efficacy and safety of anastrozole for adjuvant ... A small proportion of women treated with tamoxifen experience serious side effects including increased incidence of endometrial cancer, thromboembolism and ...

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Palliative treatment of endometrial cancer: what is the role of ... The aim of this work is to test the feasibility and safety of anastrozole as palliative treatment of endometrial cancer in elderly women ineligible for ...

9. ajog.org ajog.org/article/S0002-9378(08)00403-1/fulltext

Recurrent endometrial carcinoma regression with the use ... The authors concluded that anastrozole has minimal activity in an unselected population of patients with recurrent endometrial cancer. However, as suggested ...

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Aromatase inhibitors, tamoxifen, and endometrial cancer in ... Endometrial cancer incidence was 29% lower in the aromatase inhibitor group versus the no endocrine therapy group (hazard ratio, 0.71; 95% ...