Selinexor Maintenance Therapy for Endometrial Cancer

(ENGOT-EN5 Trial)

Recruiting at 111 trial locations

Overseen By Jonathan Berek

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Karyopharm Therapeutics Inc

Must be taking: Taxane-platinum

Must not be taking: XPO1 inhibitors, PD-1/PD-L1 immunotherapy

Disqualifiers: Sarcomas, Small cell carcinoma, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 12

Duration: Approximately 12 months

263 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a prospective, multicenter, double-blind, placebo-controlled, randomized Phase 3 study. The purpose of the study is to obtain evidence of efficacy for maintenance selinexor in participants with advanced or recurrent endometrial cancer. Participants with primary stage IV or recurrent disease who are in partial or complete response after having completed a single line of at least 12 weeks of taxane-platinum combo therapy will be randomized in a 2:1 manner to maintenance therapy with 80 milligram (mg) with selinexor once weekly (QW) or placebo until progression.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot be on any concurrent cancer therapy or investigational agents during the trial.

Is Selinexor safe for humans?

The research does not provide specific safety data for Selinexor, but it has been studied in clinical trials for endometrial cancer, suggesting it has been evaluated for safety in humans. ^{1 2 3 4 5}

How is the drug selinexor unique for treating endometrial cancer?

Selinexor is unique because it works by inhibiting exportin-1 (XPO1), which leads to the accumulation of tumor suppressor proteins like p53 in the cell nucleus, helping to control cancer growth. It is taken orally once a week and has shown significant benefits in delaying the progression of advanced or recurrent endometrial cancer, especially in patients with TP53 wild-type tumors. ^{1 2 4 6 7}

What data supports the effectiveness of the drug Selinexor for endometrial cancer?

Research shows that Selinexor, when used as a maintenance therapy, significantly delays the progression of advanced or recurrent endometrial cancer, particularly in patients with a specific type of genetic makeup (TP53 wild-type). ^{1 2 3 8 9}

Who Is on the Research Team?

Michael Kauffman, MD, PhD

Principal Investigator

Karyopharm Therapeutics Inc

Are You a Good Fit for This Trial?

This trial is for women aged 18+ with advanced or recurrent endometrial cancer who've responded to taxane-platinum chemotherapy. They must have good performance status, adequate organ function, and not be pregnant or breastfeeding. Exclusions include previous treatment with certain inhibitors or immunotherapies, recent transfusions, major surgeries, other active cancers (except some skin cancers), uncontrolled infections, and inability to swallow tablets.

Inclusion Criteria

Written informed consent in accordance with federal, local, and institutional guidelines. The participant must provide informed consent prior to the first Screening procedure

I completed a specific cancer treatment and my cancer partially or completely responded.

I can start the study drug 5-8 weeks after my last chemotherapy dose.

Exclusion Criteria

Known uncontrolled hypersensitivity to the investigational drug, or to its excipients

I have been treated with an XPO1 inhibitor before.

Concurrent treatment with an investigational agent or participation in another clinical trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive maintenance therapy with selinexor or placebo once weekly until progression

Approximately 12 months

Weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Every 12 weeks during study period, at PD and post PD at 3 and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Matching placebo for Selinexor
• Selinexor

Trial Overview The SIENDO trial tests if selinexor works as a maintenance therapy after initial successful chemotherapy in patients with endometrial cancer. Participants are randomly assigned in a 2:1 ratio to receive either selinexor (80 mg weekly) or a placebo until their disease progresses.

How Is the Trial Designed?

Group I: Selinexor Experimental Treatment 1 Intervention

Participants will receive fixed dose of selinexor 80 mg (or 60 mg for participants with a body mass index \[BMI\] less than \[\<\] 20 kilogram per meter square \[kg/m\^2\]) oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle.

Group II: Matching placebo for selinexor Placebo Group 1 Intervention

Participants will receive matching placebo for selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle.

Who Is Running the Clinical Trial?

Karyopharm Therapeutics Inc

Lead Sponsor

Trials

89

Recruited

7,200+

Richard Paulson

Karyopharm Therapeutics Inc

Chief Executive Officer since 2021

MBA from the University of Toronto's Rotman School of Management

Reshma Rangwala

Karyopharm Therapeutics Inc

Chief Medical Officer since 2023

MD, PhD

Israeli Society of Gynecologic Oncology

Collaborator

Trials

4

Recruited

1,100+

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

Belgian Gynaecological Oncology Group

Collaborator

Trials

15

Recruited

4,000+

Spanish Research Group in Ovarian Cancer

Collaborator

Trials

2

Recruited

480+

The Central and Eastern European Gynecologic Oncology Group

Collaborator

Trials

5

Recruited

1,500+

Israel Society of Gynecologic Oncology

Collaborator

Trials

2

Recruited

480+

The GOG Foundation, Inc.

Collaborator

Trials

2

Recruited

480+

Belgium and Luxembourg Gynaecological Oncology Group

Collaborator

Trials

2

Recruited

480+

North-Eastern German Society of Gynaecologic Oncology

Collaborator

Trials

2

Recruited

480+

Published Research Related to This Trial

In a study of 58 women with early-stage endometrial cancer who received postoperative hormone therapy with drospirenone/estradiol (DRSP/E2), there was no significant increase in disease recurrence or overall mortality compared to a control group of 116 women who did not receive the treatment.

The study found that while the median tumor diameter was larger in the DRSP/E2 group, factors such as disease-free survival and overall survival rates were not significantly different between the two groups, suggesting that DRSP/E2 is safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of hormone therapy with drospirenone-estradiol on endometrioid type endometrial cancer patients. Lim, S., Kim, YH., Lee, KB., et al.[2019]

In a phase III study involving 263 patients with advanced or recurrent endometrial cancer, selinexor showed a median progression-free survival (PFS) of 5.7 months compared to 3.8 months for placebo, although this difference did not reach statistical significance in the overall analysis.

A prespecified exploratory analysis indicated that patients with TP53 wild-type endometrial cancer experienced a significant improvement in PFS with selinexor, showing a median of 13.7 months compared to 3.7 months for placebo, suggesting potential efficacy in this specific subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer. Vergote, I., Pérez-Fidalgo, JA., Hamilton, EP., et al.[2023]

Progestins are effective for treating low-grade, hormone receptor-positive endometrial cancer, with some patients experiencing prolonged survival, while combination chemotherapy regimens using platinum compounds, anthracyclines, and taxanes have shown over 50% response rates and improved overall survival beyond one year in advanced cases.

Recent advances in understanding endometrial cancer at the molecular level have led to the development of new targeted therapies, which are being investigated alongside traditional treatments, although concerns about chemotherapy-related toxicities remain significant, especially in patients with existing health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developments in the systemic treatment of endometrial cancer. Mountzios, G., Pectasides, D., Bournakis, E., et al.[2018]

In a phase III trial, the XPO1 inhibitor selinexor provided a significant and lasting progression-free survival benefit for women with advanced or recurrent endometrial cancer that has a TP53 wild-type status.

This benefit was observed regardless of the microsatellite stability of the cancer, indicating that selinexor may be a broadly effective maintenance therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor Delays Wild-type TP53 Endometrial Cancer Progression. [2023]

In a study of 122 patients with high and intermediate-high risk endometrial cancer, those treated with a dose dense regimen of paclitaxel plus carboplatin showed a significantly higher three-year progression-free survival (79.5%) compared to those on the standard three-weekly protocol (57.4%).

The dose dense protocol also resulted in fewer progression events and distant metastases, along with improved overall survival in advanced stage cases, while experiencing fewer complaints of musculoskeletal pain compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose dense carboplatin paclitaxel improves progression free survival in patients with endometrial cancer. Kogan, L., Laskov, I., Amajoud, Z., et al.[2022]

The SIENDO trial indicated that selinexor may offer clinical benefits for patients with advanced or recurrent endometrial cancer who have a TP53 wild-type status.

Despite advancements in personalized medicine, recurrent endometrial cancer remains a challenging condition, highlighting the ongoing need for new treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor: Changing the paradigm in patients with TP53 wild-type endometrial cancer? Gouda, MA., Thein, KZ.[2023]

Class 3 semaphorins (SEMA3B and SEMA3F) are significantly downregulated in endometrial cancer cells compared to normal tissues, indicating their potential role as tumor suppressors.

Treatment with progesterone and 1,25-dihydroxyvitamin D(3) can upregulate SEMA3B and SEMA3F, leading to inhibited cancer cell growth and reduced invasiveness, suggesting that restoring these proteins could be a promising therapeutic strategy for endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progesterone and 1,25-dihydroxyvitamin D₃ inhibit endometrial cancer cell growth by upregulating semaphorin 3B and semaphorin 3F. Nguyen, H., Ivanova, VS., Kavandi, L., et al.[2013]

Endometrial cancer has a better prognosis when detected early, but for recurrent or metastatic cases, the median survival is only about 12 months, highlighting the need for effective treatment options.

Recent trials show that combining doxorubicin, cisplatin, and paclitaxel significantly improves response rates and overall survival compared to the standard doxorubicin plus cisplatin regimen, suggesting a more effective approach for treating advanced endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in endometrial cancer. Obel, JC., Friberg, G., Fleming, GF.[2007]

Citations

1. Korea (South) pubmed.ncbi.nlm.nih.gov

The influence of hormone therapy with drospirenone-estradiol on endometrioid type endometrial cancer patients. [2019]

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

Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Developments in the systemic treatment of endometrial cancer. [2018]

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

Selinexor Delays Wild-type TP53 Endometrial Cancer Progression. [2023]

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

Dose dense carboplatin paclitaxel improves progression free survival in patients with endometrial cancer. [2022]

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

Selinexor: Changing the paradigm in patients with TP53 wild-type endometrial cancer? [2023]

7. England pubmed.ncbi.nlm.nih.gov

Examestane in advanced or recurrent endometrial carcinoma: a prospective phase II study by the Nordic Society of Gynecologic Oncology (NSGO). [2021]

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

Progesterone and 1,25-dihydroxyvitamin D₃ inhibit endometrial cancer cell growth by upregulating semaphorin 3B and semaphorin 3F. [2013]

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

Chemotherapy in endometrial cancer. [2007]