Onapristone + Anastrozole for Endometrial Cancer

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

14 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effect of onapristone and anastrozole in treating patients with hormone receptor positive endometrial cancer that has not responded to previous treatment (refractory). Progesterone and estrogen are hormones that can cause the growth of endometrial cancer cells. Onapristone blocks the use of progesterone by the tumor cells. Anastrozole is a drug that blocks the production of estrogen in the body. Giving onapristone with anastrozole may work better than anastrozole alone in treating patients with hormone receptor positive endometrial cancer.

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.

What data supports the effectiveness of the drug combination Onapristone + Anastrozole for treating endometrial cancer?

Anastrozole, one of the drugs in the combination, has been studied for its effectiveness in treating recurrent endometrial cancer and other gynecological cancers, showing some activity in these conditions. It works by reducing estrogen levels, which can help slow the growth of hormone-dependent tumors. ^{1 2 3 4 5}

Is the combination of Onapristone and Anastrozole safe for humans?

Anastrozole (Arimidex) has been shown to have a lower incidence of gynecologic side effects compared to tamoxifen in studies for breast cancer, indicating it is generally safe for humans. However, specific safety data for the combination of Onapristone and Anastrozole is not available in the provided research. ^{1 2 5 6 7}

What makes the drug combination of Onapristone and Anastrozole unique for treating endometrial cancer?

This treatment combines Onapristone, which blocks progesterone receptors, with Anastrozole, an aromatase inhibitor that reduces estrogen production, offering a novel approach by targeting both hormone pathways in endometrial cancer, which is often hormone-dependent. ^{1 2 5 8 9}

Research Team

Tommy Buchanan, MD

Principal Investigator

Thomas Jefferson University

Eligibility Criteria

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 have fully recovered from my previous radiation treatments.

I am a woman who has gone through menopause.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of anastrozole in women with asymptomatic müllerian cancer. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Anastrozole versus tamoxifen treatment in postmenopausal women with endocrine-responsive breast cancer and tamoxifen-induced endometrial pathology. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Hormonal treatment in recurrent and metastatic gynaecological cancers: a review of the current literature. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Fertility-Sparing Treatment of Early Endometrial Cancer and Complex Atypical Hyperplasia in Young Women of Childbearing Potential. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

A lower incidence of gynecologic adverse events and interventions with anastrozole than with tamoxifen in the ATAC trial. [2018]

7. England 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Use of estrogen antagonists and aromatase inhibitors in breast cancer and hormonally sensitive tumors of the uterine body. [2007]

9. England pubmed.ncbi.nlm.nih.gov

Palliative treatment of endometrial cancer: what is the role of anastrozole in elderly women? [2021]