Nab-Sirolimus + Letrozole for Endometrial Cancer
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Aadi Bioscience, Inc.
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?A Phase 2 Multi-center Open-label Trial of nab-Sirolimus in Combination with Letrozole in Advanced or Recurrent Endometrioid Endometrial Cancer
Is the drug nab-Sirolimus a promising treatment for endometrial cancer?Yes, nab-Sirolimus is a promising treatment for endometrial cancer because similar drugs like everolimus have shown benefits in treating this type of cancer, especially when combined with letrozole. These drugs target specific pathways in cancer cells, which can help overcome resistance to other treatments and improve outcomes for patients.12456
What safety data is available for Nab-Sirolimus + Letrozole in endometrial cancer treatment?The provided research does not directly address the safety data for Nab-Sirolimus (also known as Sirolimus albumin-bound nanoparticles, ABI-009, FYARRO, Nab-rapamycin, Nab-sirolimus, TARZIFYX) combined with Letrozole in endometrial cancer treatment. However, it does mention the use of mTOR inhibitors like everolimus and sirolimus in similar contexts. Everolimus, an mTOR inhibitor, has shown clinical benefits in advanced or recurrent endometrial cancer but is associated with severe adverse effects that may lead to treatment interruption or dose reduction. A case study involving sirolimus in combination with hormone treatment for endometrial stromal sarcoma reported a partial response with minimal toxicity. These findings suggest that while mTOR inhibitors can be effective, they may also pose safety concerns that need careful management. Further specific safety data for Nab-Sirolimus combined with Letrozole would require additional studies or trials.13456
What data supports the idea that Nab-Sirolimus + Letrozole for Endometrial Cancer is an effective treatment?The available research shows that targeting the PI3K/AKT/mTOR pathway, which is often active in endometrial cancer, can help overcome resistance to hormone treatments. Studies on a similar drug, everolimus, combined with letrozole, have shown benefits for patients with recurrent endometrial cancer. This suggests that Nab-Sirolimus, which works in a similar way, could also be effective when used with letrozole. However, the specific data on Nab-Sirolimus + Letrozole for endometrial cancer is not directly provided in the available research.12456
Do I need to stop my current medications to join the trial?The trial requires you to stop taking medications that strongly interact with CYP3A4, such as certain antibiotics and antifungals, before starting nab-Sirolimus. Other medications are not specifically mentioned, so consult your doctor for guidance.
Eligibility Criteria
This trial is for adults with advanced or recurrent endometrioid endometrial cancer that can't be removed by surgery. Participants must have measurable cancer, acceptable organ function, and no severe infections or heart disease. They should not be pregnant, agree to use contraception, and cannot have certain other cancers or HIV/AIDS complications.Treatment Details
The study tests nab-Sirolimus combined with Letrozole in patients with a specific type of uterine cancer. It's an open-label Phase 2 trial where everyone gets the same treatment to see how effective it is at controlling the disease.
1Treatment groups
Experimental Treatment
Group I: Endometrioid Endometrial CancerExperimental Treatment1 Intervention
Patients with advanced or recurrent endometrioid endometrial carcinoma
nab-Sirolimus is already approved in United States, Canada for the following indications:
πΊπΈ Approved in United States as FYARRO for:
- Locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa)
π¨π¦ Approved in Canada as Sirolimus NAB for:
- Malignant perivascular epithelioid cell tumor (PEComa)
Find a clinic near you
Research locations nearbySelect from list below to view details:
Women & Infants HospitalProvidence, RI
Levine Cancer InstituteCharlotte, NC
Women's Cancer Center of NevadaLas Vegas, NV
Michael Birrer, MD, PhDLittle Rock, AR
More Trial Locations
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Who is running the clinical trial?
Aadi Bioscience, Inc.Lead Sponsor
References
Everolimus as second- or third-line treatment of advanced endometrial cancer: ENDORAD, a phase II trial of GINECO. [2022]Patients with recurrent/metastatic endometrial cancer that progresses after chemotherapy have limited treatment options and poor outcomes. Preclinical data suggest the oral mammalian target of rapamycin inhibitor everolimus may provide clinical benefit in these patients.
Phase I clinical trial of the mammalian target of rapamycin inhibitor everolimus in combination with oral topotecan for recurrent and advanced endometrial cancer. [2021]Preclinical data suggest that mammalian target of rapamycin inhibitors may potentiate the efficacy of topotecan. We evaluated the optimal schedule of oral topotecan in combination with everolimus in patients with endometrial cancer.
Reversion of Hormone Treatment Resistance with the Addition of an mTOR Inhibitor in Endometrial Stromal Sarcoma. [2021]Background. Endometrial stromal sarcomas (ESS) are a subtype of gynaecological sarcomas characterized by the overexpression of hormone receptors. Hormone treatment is widely used in ESS but primary or acquired resistance is common. The mammalian target of rapamycin (mTOR) pathway has been suggested to play a key role in the mechanisms of hormone resistance. Recent studies in breast and prostate cancer demonstrate that this resistance can be reversed with the addition of an mTOR inhibitor. This phenomenon has never been reported in ESS. Methods. We report the outcome of one patient with pretreated, progressing low grade metastatic ESS treated with medroxyprogesterone acetate in combination with the mTOR inhibitor sirolimus. Results. Partial response was achieved following the addition of sirolimus to the hormone treatment. Response has been maintained for more than 2 years with minimal toxicity and treatment is ongoing. Conclusion. This case suggests that the resistance to the hormone manipulation in ESS can be reversed by the addition of an mTOR pathway inhibitor. This observation is highly encouraging and deserves further investigation.
Synergistic in vitro anti-tumor effect of letrozole and everolimus on human endometrial carcinoma Ishikawa cells. [2021]To investigate the in vitro effect of the use of combination of letrozole and everolimus on the proliferation and apoptosis of human endometrial carcinoma Ishikawa cells.
Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma. [2021]The phosphoinositol-3 kinase (PI3K) pathway is frequently dysregulated in endometrial cancer (EC). Hormonal manipulation leads to response in some patients with EC, but resistance derived from PI3K pathway activation has been documented. Targeting mammalian target of rapamycin (mTOR) may overcome endocrine resistance. We conducted a two-institution phase II trial of everolimus and letrozole in women with recurrent EC.
Novel polymer-based system for intrauterine delivery of everolimus for anti-cancer applications. [2022]Non-surgical treatment options for low-grade endometrial cancer and precancerous lesions are a critical unmet need for women who wish to preserve fertility or are unable to undergo hysterectomy. The PI3K/AKT/mTOR pathway is frequently activated in endometrial cancers and has been associated with resistance to endocrine therapy, making it a compelling target for early stage disease. Oral everolimus, an inhibitor against mTORC1, has shown clinical benefit in advanced or recurrent disease but has severe adverse effects that may lead to treatment interruption or dose reduction. To overcome this, we developed a polymer-based intrauterine delivery system to achieve persistent, local delivery of everolimus without systemic exposure. In vivo studies, using a rat model, showed that a poly(propylene fumarate)-based rod loaded with everolimus achieved everolimus delivery to the endometrium with levels similar to oral administration, but with limited systemic exposure and up to 84 days of release. Biological activity of everolimus delivered with this system was confirmed, measured by reduced lumen epithelial cell height and PI3K pathway biomarkers. This study shows a promising new delivery approach for anti-cancer drugs for non-surgical treatment of low-grade endometrial cancer.