RECRUITING

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

Conditions

Endometrioid Endometrial Cancer Narazaciclib ON 123300 letrozole

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2023-03-29

Study Completion:2026-02

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05705505

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Must be 18 years of age, or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing informed consent form (ICF). 2. Phase 1 (Dose escalation cohorts): Have confirmed endometrial or other gynecologic malignancy that is amenable for treatment with hormonal therapy and do not have other standard treatment options. (Patients with endometrioid and other types of uterine cancer as well as ovarian cancers may be enrolled at the Investigator's discretion if hormonal based therapy is considered an appropriate option for the patient). 3. Recurrent metastatic disease or advanced (Stage IV) disease. 4. Phase 1 (Dose escalation cohorts): Patients may be enrolled regardless of prior checkpoint inhibitor therapy, at the Investigator's discretion. 5. Phase 1 (Dose escalation cohorts): Patients may be enrolled who have not received prior therapy for recurrent/metastatic disease, or have received any number of prior lines of therapy for recurrent/metastatic disease, at the Investigator's discretion. 6. Phase 1 (Dose escalation cohorts): Have either measurable or non- measurable disease. 7. Local mismatch repair (MMR) immunohistochemistry (IHC) results available (both deficient mismatch repair (dMMR) and mismatch repair protein (MMRP) deficiency (MMRp) patients are eligible, and will be documented for research purposes). 8. Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1. 9. Tissue for estrogen/progesterone receptor status and molecular classification (paraffin embedded or fresh biopsy if unavailable). 10. Have adequate organ function as indicated by the following: 1. Absolute neutrophil count (ANC) ≥1.0×109/L 2. Platelets ≥100×109/L 3. Hemoglobin ≥9.0 g/dL 4. International Normalized Ratio (INR) ≤1.5 5. Serum creatinine ≤1.5 times ULN, or estimated creatinine clearance (calculated according to normal institutional practice) greater than 50 milliliters (ml)/min 6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) below 3.0×the upper limit of normal (ULN) (or ALT and AST ≤5×ULN if liver metastases are present). 7. Total serum bilirubin \<1.5×ULN; or total bilirubin ≤3.0×ULN with direct bilirubin within normal range of the central laboratory in participants with well documented Gilbert's Syndrome. 11. Have baseline corrected QT (QTc) interval \<470 msec. 12. Are able to swallow oral medications. 13. Have a life expectancy of at least 12 weeks 14. Sex and Contraceptive/Barrier Requirements 15. Are capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.	1. Phase 1 (Dose escalation cohorts): Cancer other than endometrial or other gynecologic malignancy. 2. Have received a cyclin-dependent kinase (CDK) 4/6 inhibitor in the past. 3. Have any significant medical condition, laboratory abnormality, or psychiatric illness that, in the opinion of the Investigator, would prevent the patient from participating in the study or present an unacceptable risk to the patient. 4. Are at risk for Torsades de pointes (TdP): Patients who have a marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval \>470 msec) using Fredericia's QT correction formula, or who have a history of additional risk factors for TdP (eg, heart failure, hypokalemia, family history of Long QT Syndrome), or who are currently taking medications that prolong the QT/QTc interval. 5. Have uncontrolled intercurrent or significant medical illness, serious underlying medical condition, abnormal laboratory finding, or psychiatric illness/social situation that might, in the Investigator's or the Sponsor's judgment, prevent the participant from receiving study treatment or being followed in this study, or otherwise renders the participant inappropriate for the study, including but not limited to ongoing or active infection, bleeding, congestive heart failure, unstable angina, cardiac arrhythmia, oxygen-dependent lung disease, and psychiatric illness/social situations that limit participation compliance with study procedures and requirements. 6. Are currently taking or within 5 half-lives of taking strong inducers and inhibitors of cytochrome P450 enzyme (CYP)2C8 and CYP3A4. 7. Have a recent history of venous thromboembolic events, defined as event occurring \<6 months prior to screening and also currently on therapy, known underlying hypercoagulability, or a major thromboembolic event within the past 2 years. 8. Have baseline Grade ≥2 diarrhea. 9. Have Grade ≥3 hypercalcemia (corrected serum calcium \>12.5 mg/dL). 10. Are pregnant or nursing mothers. 11. Have had major surgery within 14 days prior to screening to allow for postoperative healing of the surgical wound and site(s). 12. Have received recent (within 28 days prior to screening) live attenuated vaccines. 13. Have active infection, including bacterial or fungal infections or active viral infection or viral load, including any human immunodeficiency virus (HIV), or hepatitis B virus (HBV), hepatitis C virus (HCV), or Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (COVID-19). 14. Currently have or have been treated in the past 2 years, for any other cancer or malignancy, except: 1. Non-melanoma skin cancer, including basal cell carcinoma of the skin 2. Curatively treated carcinoma in situ of the cervix. 15. Have any clinically significant, uncontrolled heart disease, and/or cardiac repolarization abnormality, or a history of any of the following: 1. Syncope of cardiovascular etiology 2. Ventricular arrhythmia of pathological origin 3. Sudden cardiac arrest 4. Documented history of congestive heart failure with reduced ejection fraction. 16. Have interstitial pneumonia or has severe impairment of lung function defined as: 1. Vital capacity and diffusing capacity of the lung for carbon monoxide (DLCO) of ≤50% of the normal predicted values, or 2. Oxygen (O2) saturation at rest in ambient environment of ≤88%. 17. Have received within the 21 days prior to screening, is currently receiving, or intends to receive during the study any nonstudy anticancer therapy, including but not limited to any of the following: 1. Anticancer agent 2. Investigational agent 3. Surgical intervention 4. Radiation intervention, including any radiation therapy (includes radiation to an isolated lesion). (Palliative radiation, prior to screening, to lesions that are not target lesions is permissible). 18. Have central nervous system metastases or leptomeningeal carcinomatosis. 19. Have history of or current/active uveitis. 20. Are not candidates for treatment with letrozole

Inclusion Criteria

Exclusion Criteria

1. Must be 18 years of age, or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing informed consent form (ICF).
2. Phase 1 (Dose escalation cohorts): Have confirmed endometrial or other gynecologic malignancy that is amenable for treatment with hormonal therapy and do not have other standard treatment options. (Patients with endometrioid and other types of uterine cancer as well as ovarian cancers may be enrolled at the Investigator's discretion if hormonal based therapy is considered an appropriate option for the patient).
3. Recurrent metastatic disease or advanced (Stage IV) disease.
4. Phase 1 (Dose escalation cohorts): Patients may be enrolled regardless of prior checkpoint inhibitor therapy, at the Investigator's discretion.
5. Phase 1 (Dose escalation cohorts): Patients may be enrolled who have not received prior therapy for recurrent/metastatic disease, or have received any number of prior lines of therapy for recurrent/metastatic disease, at the Investigator's discretion.
6. Phase 1 (Dose escalation cohorts): Have either measurable or non- measurable disease.
7. Local mismatch repair (MMR) immunohistochemistry (IHC) results available (both deficient mismatch repair (dMMR) and mismatch repair protein (MMRP) deficiency (MMRp) patients are eligible, and will be documented for research purposes).
8. Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
9. Tissue for estrogen/progesterone receptor status and molecular classification (paraffin embedded or fresh biopsy if unavailable).
10. Have adequate organ function as indicated by the following:
1. Absolute neutrophil count (ANC) ≥1.0×109/L
2. Platelets ≥100×109/L
3. Hemoglobin ≥9.0 g/dL
4. International Normalized Ratio (INR) ≤1.5
5. Serum creatinine ≤1.5 times ULN, or estimated creatinine clearance (calculated according to normal institutional practice) greater than 50 milliliters (ml)/min
6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) below 3.0×the upper limit of normal (ULN) (or ALT and AST ≤5×ULN if liver metastases are present).
7. Total serum bilirubin \<1.5×ULN; or total bilirubin ≤3.0×ULN with direct bilirubin within normal range of the central laboratory in participants with well documented Gilbert's Syndrome.
11. Have baseline corrected QT (QTc) interval \<470 msec.
12. Are able to swallow oral medications.
13. Have a life expectancy of at least 12 weeks
14. Sex and Contraceptive/Barrier Requirements
15. Are capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

1. Phase 1 (Dose escalation cohorts): Cancer other than endometrial or other gynecologic malignancy.
2. Have received a cyclin-dependent kinase (CDK) 4/6 inhibitor in the past.
3. Have any significant medical condition, laboratory abnormality, or psychiatric illness that, in the opinion of the Investigator, would prevent the patient from participating in the study or present an unacceptable risk to the patient.
4. Are at risk for Torsades de pointes (TdP): Patients who have a marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a QTc interval \>470 msec) using Fredericia's QT correction formula, or who have a history of additional risk factors for TdP (eg, heart failure, hypokalemia, family history of Long QT Syndrome), or who are currently taking medications that prolong the QT/QTc interval.
5. Have uncontrolled intercurrent or significant medical illness, serious underlying medical condition, abnormal laboratory finding, or psychiatric illness/social situation that might, in the Investigator's or the Sponsor's judgment, prevent the participant from receiving study treatment or being followed in this study, or otherwise renders the participant inappropriate for the study, including but not limited to ongoing or active infection, bleeding, congestive heart failure, unstable angina, cardiac arrhythmia, oxygen-dependent lung disease, and psychiatric illness/social situations that limit participation compliance with study procedures and requirements.
6. Are currently taking or within 5 half-lives of taking strong inducers and inhibitors of cytochrome P450 enzyme (CYP)2C8 and CYP3A4.
7. Have a recent history of venous thromboembolic events, defined as event occurring \<6 months prior to screening and also currently on therapy, known underlying hypercoagulability, or a major thromboembolic event within the past 2 years.
8. Have baseline Grade ≥2 diarrhea.
9. Have Grade ≥3 hypercalcemia (corrected serum calcium \>12.5 mg/dL).
10. Are pregnant or nursing mothers.
11. Have had major surgery within 14 days prior to screening to allow for postoperative healing of the surgical wound and site(s).
12. Have received recent (within 28 days prior to screening) live attenuated vaccines.
13. Have active infection, including bacterial or fungal infections or active viral infection or viral load, including any human immunodeficiency virus (HIV), or hepatitis B virus (HBV), hepatitis C virus (HCV), or Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (COVID-19).
14. Currently have or have been treated in the past 2 years, for any other cancer or malignancy, except:
1. Non-melanoma skin cancer, including basal cell carcinoma of the skin
2. Curatively treated carcinoma in situ of the cervix.
15. Have any clinically significant, uncontrolled heart disease, and/or cardiac repolarization abnormality, or a history of any of the following:
1. Syncope of cardiovascular etiology
2. Ventricular arrhythmia of pathological origin
3. Sudden cardiac arrest
4. Documented history of congestive heart failure with reduced ejection fraction.
16. Have interstitial pneumonia or has severe impairment of lung function defined as:
1. Vital capacity and diffusing capacity of the lung for carbon monoxide (DLCO) of ≤50% of the normal predicted values, or
2. Oxygen (O2) saturation at rest in ambient environment of ≤88%.
17. Have received within the 21 days prior to screening, is currently receiving, or intends to receive during the study any nonstudy anticancer therapy, including but not limited to any of the following:
1. Anticancer agent
2. Investigational agent
3. Surgical intervention
4. Radiation intervention, including any radiation therapy (includes radiation to an isolated lesion). (Palliative radiation, prior to screening, to lesions that are not target lesions is permissible).
18. Have central nervous system metastases or leptomeningeal carcinomatosis.
19. Have history of or current/active uveitis.
20. Are not candidates for treatment with letrozole

Contacts and Locations

Study Contact

Victor Moyo, MD

CONTACT

484 535 1402

vmoyo@onconova.us

Principal Investigator

Victor Moyo, MD

STUDY_CHAIR

Onconova Therapeutics

Study Locations (Sites)

Arizona Oncology Associates, PC - HOPE

Tucson, Arizona, 85711

United States

Minnesota Oncology Hematology, P.A.

Minneapolis, Minnesota, 55404

United States

Perlmutter Cancer Center at NYU Langone Hospital - Long Island

Mineola, New York, 11501

United States

NYU Langone

New York, New York, 10016

United States

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, 97401

United States

Greenville Health System, Institute for Oncology Clinical Research

Greenville, South Carolina, 29605

United States

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246

United States

Texas Oncology - Fort Worth Cancer Center

Fort Worth, Texas, 76104

United States

Collaborators and Investigators

Sponsor: Traws Pharma, Inc.

Victor Moyo, MD, STUDY_CHAIR, Onconova Therapeutics

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-03-29

Study Completion Date2026-02

Study Record Updates

Study Start Date2023-03-29

Study Completion Date2026-02

Terms related to this study

Keywords Provided by Researchers

Narazaciclib
ON 123300
letrozole

Additional Relevant MeSH Terms

Endometrioid Endometrial Cancer