Narazaciclib + Letrozole for Endometrial Cancer

Recruiting in Palo Alto (17 mi)

+7 other locations

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Traws Pharma, Inc.

Must be taking: Letrozole

Must not be taking: CDK 4/6 inhibitors

Disqualifiers: Other cancers, Heart disease, Infections, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests narazaciclib with letrozole in patients with recurring and spreading gynecologic cancers. It aims to find the safest and most effective dose of narazaciclib. The combination works by directly attacking cancer cells and reducing hormone levels that help these cells grow.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot take strong inducers and inhibitors of certain liver enzymes (CYP2C8 and CYP3A4) within 5 half-lives before starting the trial.

What data supports the effectiveness of the drug combination Narazaciclib and Letrozole for endometrial cancer?

Research shows that letrozole, an aromatase inhibitor, has been effective in treating endometrial cancer by affecting hormone levels. Additionally, a study combining letrozole with another drug, ribociclib, showed positive results in patients with relapsed estrogen receptor-positive endometrial cancer, suggesting potential benefits of combining letrozole with other drugs.

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What safety data exists for the treatment with Narazaciclib and Letrozole?

Letrozole, also known as Femara, has been studied for safety in various conditions, including endometrial cancer and endometriosis. It has been used in combination with other treatments and generally shows a safety profile that is acceptable for clinical use, although specific safety data for Narazaciclib is not provided in the available research.

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How is the drug Narazaciclib + Letrozole unique for treating endometrial cancer?

This treatment combines Narazaciclib with Letrozole, an aromatase inhibitor that reduces estrogen levels, which can help slow the growth of endometrial cancer. The combination is novel as it may enhance the effectiveness of Letrozole by targeting cancer cells in a new way, potentially offering a more effective option compared to Letrozole alone.

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Eligibility Criteria

This trial is for adults with recurrent metastatic low-grade endometrioid endometrial cancer who can swallow pills, have had up to two prior systemic treatments (excluding certain therapies), and whose major organs function well. They must not be pregnant, agree to use contraception if applicable, and have a life expectancy of at least 12 weeks.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My endometrial cancer is low-grade and mostly endometrioid.

I have previously received immunotherapy for my cancer, if it was available and not advised against for me.

Exclusion Criteria

My cancer is not related to the uterus or other female reproductive organs.

My cancer is not a low-grade or early-stage type.

I do not have any serious heart conditions that are not under control.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Phase 1 Treatment

Eligible patients are enrolled in escalating dose cohorts of narazaciclib in combination with letrozole in 28-day cycles to determine the maximum tolerated dose and recommended phase 2 dose.

28 days per cycle

Multiple visits per cycle for dose escalation and monitoring

Phase 2a Treatment

Patients receive narazaciclib and letrozole at the recommended phase 2 dose in 28-day cycles until disease progression, withdrawal, or unacceptable toxicity.

Until disease progression or withdrawal

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and overall survival assessments.

Up to 2 years after end of treatment

Periodic visits for follow-up assessments

Participant Groups

The study tests increasing doses of narazaciclib combined with a standard dose of letrozole in patients with specific gynecologic cancers. It aims to determine the safety and effectiveness of this combination treatment.

Group I: Escalating daily doses of narazaciclib in combination with letrozole (2.5mg day) Experimental Treatment 2 Interventions

Phase 1: Initiating at 160mg per day of narazaciclib, patients will receive escalating doses of narazaciclib (oral tablets/once daily) in combination with 2.5mg of letrozole (oral tablet/once daily). Phase 2: All patients will receive the recommended phase 2 dose (RP2D) of the combination of narazaciclib (oral tablets) and letrozole (oral tablet/QD)

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

🇺🇸 Approved in United States as Femara for:

• Breast cancer in postmenopausal women
• Increasing the chance of ovulation in women with polycystic ovary syndrome

🇪🇺 Approved in European Union as Letrozole for:

• Early breast cancer in postmenopausal women
• Advanced breast cancer in postmenopausal women

🇨🇦 Approved in Canada as Letrozole for:

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Greenville Health System, Institute for Oncology Clinical Research Greenville, SC

Arizona Oncology Associates, PC - HOPE Tucson, AZ

Minnesota Oncology Hematology, P.A. Minneapolis, MN

Texas Oncology - Fort Worth Cancer Center Fort Worth, TX

More Trial Locations

Who Is Running the Clinical Trial?

Traws Pharma, Inc. Lead Sponsor

Onconova Therapeutics, Inc. Lead Sponsor

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant therapy of endometrial cancer with the aromatase inhibitor letrozole: endocrine and clinical effects. [2019] To investigate the short-term hormonal and clinical effects of the aromatase inhibitor letrozole (Femara) in patients with endometrial cancer.

2. England pubmed.ncbi.nlm.nih.gov

Gonadotropin-Releasing Hormone Agonist Combined With a Levonorgestrel-Releasing Intrauterine System or Letrozole for Fertility-Preserving Treatment of Endometrial Carcinoma and Complex Atypical Hyperplasia in Young Women. [2018] The aim of this study was to evaluate the efficacy and safety with gonadotropin-releasing hormone agonist (GnRHa) combined with a levonorgestrel-releasing intrauterine system or an aromatase inhibitor (letrozole) in young women with well-differentiated early endometrial carcinoma (EC) and complex atypical hyperplasia (CAH).

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

ICI-Chemo New Standard for Endometrial Cancer. [2023] The phase III RUBY and NRG-GY018 trials indicate that women with advanced endometrial cancer whose disease is newly diagnosed or has recurred for the first time benefit from the combination of a PD-1 inhibitor with standard chemotherapy. Adding either dostarlimab or pembrolizumab significantly prolonged progression-free survival, with overall survival also trending in the right direction.

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

Phase II trial of ribociclib and letrozole in patients with relapsed oestrogen receptor-positive ovarian or endometrial cancers. [2021] We describe a phase II clinical trial of the combination of ribociclib and letrozole for treatment of relapsed oestrogen receptor (ER)-positive ovarian cancer (OC) and endometrial cancer (EC). The primary endpoint was the proportion of patients alive, progression-free survival (PFS), and still on treatment at 12 weeks (PFS12), with 45% or greater considered positive.

5. Brazil pubmed.ncbi.nlm.nih.gov

Effect of letrozole in carcinogen-plus-estrogen-induced endometrial hyperplasia in mice. [2019] To evaluate the effects of letrozole (Ltz) in carcinogen+estrogen-induced endometrial hyperplasia.

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

Effects of aromatase inhibitors on proliferation and apoptosis in eutopic endometrial cell cultures from patients with endometriosis. [2006] To study the effect of letrozole (Let) and anastrozole (Anas) on apoptosis and cell proliferation in epithelial endometrial cells (EEC) from patients with endometriosis (EDT).

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Criteria for evaluating the effectiveness of aromatase inhibitors in the neoadjuvant treatment of patients with endometrial carcinoma]. [2018] Clinical and experimental effects of neoadjuvant treatment of endometrial cancer patients with non-steroidal aromatase inhibitors: letrozole (femara, n=10, 2.5 mg/day, 14 days), anastrozole (arimidex, n=15,1 mg/day, 28 days) and exemestane (aromazine, n=13, 25 mg/day, 14 days) were compared. Administration of anastrozole was mostly frequently followed by pain relief in the lower abdomen and/or decreased rates of uterine discharge. Endometrial wall thickness (M-echo signal) decreased significantly in 60% of patients receiving anastrozole, exemestane - 58.3% and letrozole - 40%. Substantial drop in intratumoral aromatase and blood estradiol levels occurred more frequently after anastrozole and letrozole while progesterone receptor levels in tumor were markedly lower after exemestane administration. Assay of blood LH (except letrozole), FSH and cholesterol appeared to be of less relevance. On the contrary, significance of assessment of marker Ki-67 expression, which, in the case of anastrozole, dropped in 6 out of 12 patients after a 28-day course, could hardly be underestimated.

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

Oncological and reproductive outcomes for gonadotropin-releasing hormone agonist combined with aromatase inhibitors or levonorgestrel-releasing intra-uterine system in women with endometrial cancer or atypical endometrial hyperplasia. [2023] To evaluate the efficacy and safety of gonadotropin-releasing hormone agonist (GnRHa) combined with a levonorgestrel-releasing intrauterine device (LNG-IUD) or aromatase inhibitor (letrozole) in women with endometrial carcinoma or atypical endometrial hyperplasia who wished to preserve fertility.