Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Herbal and Botanical

Letrozole

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Orange

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)

Orange tablets, each containing 40 mg or 120 mg of narazaciclib as narazaciclib monolactate

Narazaciclib

Letrozole 2.5mg

Victor Moyo, MD

Stacey Kimbell, RN

Julie Klinker, RN

Joseph Buscema, MD

Brianna Lenox

Timothy G Larson, MD

Bhavana Pothuri, MD

Jeanne Schaffer, RN, BSN

Nichole Fisher, RN, BSN

Charles K Anderson, MD

Fiona Davidson

Lisa Johnson

W. Jeff Edenfield, MD

Christine Terraciano

Noelle G Cloven, MD

Nori Sullivan, RN, BSN

This study will assess the safety and efficacy of increasing doses of narazaciclib (ON 123300) in combination with the standard daily dose (2.5mg) of letrozole in patients with Recurrent Metastatic Low-grade Endometrioid Endometrial Cancer and other Gynecologic Malignancies.

This is a phase 1/2a, open-label, multicenter study to evaluate the safety, tolerability and efficacy of escalating doses of narazaciclib (ON 123300) in combination with letrozole for patients with recurrent metastatic low-grade endometrioid endometrial cancer and other Gynecologic Malignancies. Pharmacokinetics and pharmacodynamics will also be assessed.

In Phase 1, eligible patients will be enrolled to escalating dose cohorts. Cohorts will receive escalating doses of oral narazaciclib starting at 160 mg orally, once daily, in combination with letrozole 2.5 mg orally, once daily, in 28-day cycles in a typical 3 + 3 design. The dose of narazaciclib will be increased in 40 mg/day increments from cohort to cohort until the maximum tolerated dose (MTD) and/or the minimal biologically effective dose (MBED) of narazaciclib orally, once daily, in combination with letrozole 2.5 mg orally, once daily, is reached and the RP2D of the combination is established. Three to 6 patients will be enrolled per dose cohort in phase 1.

In Phase 2a, narazaciclib and letrozole at the RP2D established in Phase 1 will be administered to approximately 30 eligible patients with documented recurrent metastatic LGEEC for 28-day cycles. Treatment will continue until disease progression, patient withdrawal, or unacceptable drug-related toxicity.

Phase 1: 3+3 dose escalation Phase2: Expansion cohort

Study of Narazaciclib (ON 123300) Plus Letrozole in Endometrial Cancer and Other Gynecologic Malignancies

A Multi-center Phase 1/2a Study of Narazaciclib (ON 123300) in Combination With Letrozole as Therapy for the Treatment of Recurrent Metastatic Endometrial Cancer and Other Gynecologic Malignancies

Highest concentration of drug measured in the PK samples

Time from dosing until collection of the PK samples with the highest drug concentration.

The area under the concentration-time curve from dosing (time 0) to time t.

Tyrosine kinase 1 (TK1) is a metabolic enzyme fundamentally involved in DNA synthesis that plays a critical role in cell proliferation

Percentage of patients experiencing TEAEs, by system organ class (SOC) and preferred term

Progression or other status determined by RECIST assessment

Time from first dose to progression by RECIST assessment. A Kaplan-Meier curve will be provided.

Percentage of patients achieving a CR by RECIST

Percentage of patients achieving a PR by RECIST

Percentage of patients maintaining SD by RECIST

Percentage of patients achieving a CR or PR by RECIST

Percentage of patients achieving a CR or PR or maintaining SD by RECIST

Time from definition of response to diagnosis of progression. A Kaplan-Meier curve will be provided.

Time from first dose until definition of response. A Kaplan-Meier curve will be provided.

Time from first dose until death from any cause. A Kaplan-Meier curve will be provided.

Traws Pharma, Inc.

30 patients diagnosed with SP endometrial ca

32 patients diagnosed with Endometrioid endometrial ca

no intervention

P16 is a tumor suppressor protein implicated in serous papillary endometrial carcinoma. Evidence from previous trials indicates that it may be used as a diagnostic biomarker distinguishing this disease from endometrioid endometrial cancer. Additional evidence points to its prognostic value.

The current study will evaluate p16 both as a diagnostic tool for serous papillary endometrial cancer and as a prognostic biomarker.

following anonymization, histology blocks will be microtomed and stained for P16 and P53 proteins.

Blocks from endometrioid endometrial cancer will be used as a control group.

Existing paraffin pathology blocks in hospital's library were used. Remainder of material was returned to the library.

No identifying features were retained or attached to specimens.

P16 Staining as Prognostic Biomarker in Serous Papillary Endometrial Cancer

Expression of the P16 Protein in Serous Papillary Endometrial Cancer, and Its Clinical and Prognostic Significance

Rambam Health Care Campus

Dr. Itamar Netzer

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Anti-Infective Agents

Sirolimus

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

Patients with advanced or recurrent endometrioid endometrial carcinoma

Prospective Phase 2, open-label, multi-institutional study to evaluate the efficacy and safety of nab-sirolimus + letrozole in patients

nab-sirolimus

Aadi Bioscience Medical Information

Aaron Holley

Matthew Kovak

Michelle McClosky

Brian Slomovitz, MD

Thania Escamilla

Jacky Amador

Nicola M Spirtos, MD

Angela Green, MD

Leah J Wilson, BS, RN, OCN

Allison M Puechi, MD

Christine Pappaterra

Lauren Dockery, MD

Pamela Smith

Cara Mathews, MD

Shelly Maxfield, CCRP

Anna Priebe, MD

Anh Lam

Fernanda Musa, MD

Willis Navarro, MD

A Phase 2 Multi-center Open-label Trial of nab-Sirolimus in Combination with Letrozole in Advanced or Recurrent Endometrioid Endometrial Cancer

This is a prospective phase 2, open-label, multi-institutional study to evaluate the efficacy and safety of nab-sirolimus + letrozole in patients with advanced or recurrent endometrioid endometrial carcinoma who have received 0-1 prior lines of chemotherapy in the recurrent/metastatic setting. Patients will be treated with nab-sirolimus (given IV on Days 1 and 8 in a 21-day cycle, combined with letrozole (orally, daily) until unacceptable toxicity or disease progression, or until in the opinion of the Investigator the patient is no longer benefiting from therapy, or at patient discretion.

Trial of Nab-Sirolimus in Combination With Letrozole in Patients With Advanced or Recurrent Endometrioid Endometrial Cancer

A Phase 2 Multi-center Open-label Trial of Nab-Sirolimus in Combination With Letrozole in Advanced or Recurrent Endometrioid Endometrial Cancer

ORR, defined as the proportion of patients with best overall response (BOR) of confirmed partial response (PR) or complete response (CR) from the time of study treatment initiation until progression of disease (PD) as determined by the Investigator using RECIST v1.1.

Determined for patients with BOR of confirmed CR or PR

BOR of confirmed CR or PR (either of any duration) or stable disease (SD) following study treatment initiation (by IRR)

Time from study treatment initiation to initial measurement of CR or PR, where CR or PR is subsequently confirmed

Number of months from study treatment initiation to the date of disease progression 3 or death due to any cause

Number of months from study treatment initiation to the date of death due to any cause or last follow up date if alive

Of treatment-emergent and treatment-related adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Narazaciclib (ON 123300) Plus Letrozole in Endometrial Cancer and Other Gynecologic Malignancies	NCT05705505	Endometrioid En...	Narazaciclib Letrozole 2.5mg	18 Years -	Traws Pharma, Inc.
P16 Staining as Prognostic Biomarker in Serous Papillary Endometrial Cancer	NCT01267357	Serous Papillar...	no intervention	18 Years -	Rambam Health Care Campus
Trial of Nab-Sirolimus in Combination With Letrozole in Patients With Advanced or Recurrent Endometrioid Endometrial Cancer	NCT05997017	Endometrial Can... Endometrioid Tu... Cancer Tumor Recurrent Endom... Endometrioid En...	nab-sirolimus	18 Years -	Aadi Bioscience, Inc.

Spots Global Cancer Trial Database for endometrioid endometrial cancer