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Endometrioid Endometrial CancerPhase 1/2NCT05705505

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

A Phase 1/2 study testing Narazaciclib and Letrozole 2.5mg in people with Endometrioid Endometrial Cancer, run by Traws Pharma, Inc. at 8 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Endometrioid Endometrial Cancer
What is being tested?
Narazaciclib and Letrozole 2.5mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
8 sitesUnited States
Study dates
29 Mar 2023to Feb 2026
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
  • 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).
  • OR Phase 2a (Dose expansion cohort): Have confirmed low-grade (Federation of Gynaecology and Obstetrics [FIGO] Grade 1 or 2) endometrioid endometrial cancer (LGEEC). Mixed tumor histology is allowed if the non-endometrioid component is <5%.
  • Recurrent metastatic disease or advanced (Stage IV) disease.
  • Phase 1 (Dose escalation cohorts): Patients may be enrolled regardless of prior checkpoint inhibitor therapy, at the Investigator's discretion.
  • OR Phase 2a (Dose expansion cohort): Have received prior checkpoint inhibitor therapy (single agent or in combination with another anti-cancer therapy) if available for this indication and NOT contraindicated.
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  • 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.
  • OR Phase 2a (Dose expansion cohort): Have received 1 or 2 prior lines of systemic therapy for metastatic disease. Patient has NOT received more than 2 prior lines of systemic therapy for metastatic LGEEC (including checkpoint inhibitor, hormone therapy, or chemotherapy). Prior external beam radiotherapy, brachytherapy, and/or surgery for localized disease is allowed and is not counted as a line of therapy.
  • Phase 1 (Dose escalation cohorts): Have either measurable or non- measurable disease.
  • OR Phase 2a (Dose expansion cohort): Have measurable disease outside the radiated field.
  • 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).
  • Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
  • Tissue for estrogen/progesterone receptor status and molecular classification (paraffin embedded or fresh biopsy if unavailable).
  • Have adequate organ function as indicated by the following:
  • Absolute neutrophil count (ANC) ≥1.0×109/L
  • Platelets ≥100×109/L
  • Hemoglobin ≥9.0 g/dL
  • International Normalized Ratio (INR) ≤1.5
  • Serum creatinine ≤1.5 times ULN, or estimated creatinine clearance (calculated according to normal institutional practice) greater than 50 milliliters (ml)/min
  • 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).
  • 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.
  • Have baseline corrected QT (QTc) interval <470 msec.
  • Are able to swallow oral medications.
  • Have a life expectancy of at least 12 weeks
  • Sex and Contraceptive/Barrier Requirements
  • Are postmenopausal, defined as: i) Patient's last menstrual period occurred more than 12 months prior to screening without any alternative medical cause, and ii) Patient's postmenopausal status is confirmed by screening serum follicle-stimulating hormone concentration of >40 milli-International unit/ml (mIU/mL); or iii) Patient has undergone surgical sterilization (bilateral oophorectomy and/or hysterectomy) OR b) Must have a negative pregnancy test at screening and upon study entry (Cycle 1 Day 1) if not postmenopausal and c) Contraceptive use must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies if not postmenopausal.
  • Patients under 55 years with intact ovaries will undergo hormonal verification.
  • Are capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Who cannot join

  • Phase 1 (Dose escalation cohorts): Cancer other than endometrial or other gynecologic malignancy.
  • OR Phase 2a (Dose expansion cohort): Non-low-grade EEC (not FIGO Grades 1 or 2) or non-endometrioid adenocarcinoma, sarcoma, small cell carcinoma with neuroendocrine differentiation, or non-epithelial cancers as exclusion criteria.
  • Have received a cyclin-dependent kinase (CDK) 4/6 inhibitor in the past.
  • 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.
  • 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.
  • 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.
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  • Are currently taking or within 5 half-lives of taking strong inducers and inhibitors of cytochrome P450 enzyme (CYP)2C8 and CYP3A4.
  • 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.
  • Have baseline Grade ≥2 diarrhea.
  • Have Grade ≥3 hypercalcemia (corrected serum calcium >12.5 mg/dL).
  • Are pregnant or nursing mothers.
  • Have had major surgery within 14 days prior to screening to allow for postoperative healing of the surgical wound and site(s).
  • Have received recent (within 28 days prior to screening) live attenuated vaccines.
  • 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).
  • Currently have or have been treated in the past 2 years, for any other cancer or malignancy, except:
  • Non-melanoma skin cancer, including basal cell carcinoma of the skin
  • Curatively treated carcinoma in situ of the cervix.
  • Have any clinically significant, uncontrolled heart disease, and/or cardiac repolarization abnormality, or a history of any of the following:
  • Syncope of cardiovascular etiology
  • Ventricular arrhythmia of pathological origin
  • Sudden cardiac arrest
  • Documented history of congestive heart failure with reduced ejection fraction.
  • Have interstitial pneumonia or has severe impairment of lung function defined as:
  • Vital capacity and diffusing capacity of the lung for carbon monoxide (DLCO) of ≤50% of the normal predicted values, or
  • Oxygen (O2) saturation at rest in ambient environment of ≤88%.
  • 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:
  • Anticancer agent
  • Investigational agent
  • Surgical intervention
  • 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).
  • Have central nervous system metastases or leptomeningeal carcinomatosis.
  • Have history of or current/active uveitis.
  • Are not candidates for treatment with letrozole

Trial locations and contacts

8 sites in 1 country.

Victor Moyo, MD contact

484 535 1402

vmoyo@onconova.us

8 sites in 1 country

United States8 sites, 8 recruiting

  • Texas Oncology-Baylor Charles A. Sammons Cancer Center

    Dallas, Texas, 75246

    Christine Terraciano, 214-370-1942, christine.terraciano@usoncology.com

    Noelle G Cloven, MD

    Recruiting

  • Willamette Valley Cancer Institute and Research Center

    Eugene, Oregon, 97401

    Jeanne Schaffer, RN, BSN, 541-736-3385, jeanne.schaffer@usoncology.com

    Nichole Fisher, RN, BSN, 541-988-0656, nichole.fisher@usoncology.com

    Recruiting

  • Texas Oncology - Fort Worth Cancer Center

    Fort Worth, Texas, 76104

    Nori Sullivan, RN, BSN, 817-413-1760, nori.sullivan@usoncology.com

    Noelle G Cloven, MD

    Recruiting

  • Greenville Health System, Institute for Oncology Clinical Research

    Greenville, South Carolina, 29605

    Fiona Davidson, 864-455-3600, Fiona.Davidson@prismahealth.org

    Lisa Johnson, 864-455-3600, Lisa.Johnson@prismahealth.org

    Recruiting

  • Perlmutter Cancer Center at NYU Langone Hospital - Long Island

    Mineola, New York, 11501

    CT.gov@nyulangone.org

    Bhavana Pothuri, MD

    Recruiting

  • Minnesota Oncology Hematology, P.A.

    Minneapolis, Minnesota, 55404

    Brianna Lenox, 612-884-6329, Brianna.Lenox@usoncology.com

    Timothy G Larson, MD

    Recruiting

  • NYU Langone

    New York, New York, 10016

    CT.gov@nyulangone.org

    Bhavana Pothuri, MD

    Recruiting

  • Arizona Oncology Associates, PC - HOPE

    Tucson, Arizona, 85711

    Stacey Kimbell, RN, 520-668-5678, stacey.kimbell@usoncology.com

    Julie Klinker, RN, 520-269-3821, julie.klinker@usoncology.com

    Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

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.

Being tested
Narazaciclib, Letrozole 2.5mg
Keywords
Narazaciclib, ON 123300, letrozole

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NarazaciclibDrug

    Also called ON 123300, HX-301

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

  • Letrozole 2.5mgDrug

    Also called Femara

    Tablet

Study groups in NCT05705505
Study groupRoleWhat they receive
Escalating daily doses of narazaciclib in combination with letrozole (2.5mg day)ExperimentalPhase 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)
Receives: Drug: Narazaciclib; Drug: Letrozole 2.5mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicities (DLTs) will be tabulated and summarized by cohort

    Number of DLTs per cohort

    Measured: From First dose until end of Cycle 1 (28 days)

  2. Treatment-emergent adverse events (TEAEs), including DLTs will be graded by CTCAE v5.0

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

    Measured: From first dose until 30 days after final dose, up to approximately 1 year

  3. Phase 2 - Progression-free survival (PFS) at 24 weeks by Investigator assessment

    Progression or other status determined by RECIST assessment

    Measured: Measured from first dose until 24-weeks

Secondary outcomes (10)

  1. PFS at 16 weeks by Investigator assessment

    Progression or other status determined by RECIST assessment

    Measured: Measured from first dose until 16-weeks

  2. Median PFS by Investigator assessment

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

    Measured: Measured from first dose until diagnosis of progression including 2 years of follow-up after discontinuation of treatment.

  3. Complete response (CR) rate

    Percentage of patients achieving a CR by RECIST

    Measured: From first dose until occurrence of response or progression, up to 1 year

  4. Partial response (PR) rate

    Percentage of patients achieving a PR by RECIST

    Measured: From first dose until occurrence of response or progression, up to 1 year

  5. Stable disease (SD) rate

    Percentage of patients maintaining SD by RECIST

    Measured: From first dose until occurrence of response or progression, up to 1 year

  6. Overall response rate (ORR equals CR + PR)

    Percentage of patients achieving a CR or PR by RECIST

    Measured: From first dose until occurrence of response or progression, up to 1 year

  7. Disease control rate (DCR equals CR+PR+SD)

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

    Measured: From first dose until occurrence of response or progression, up to 1 year

  8. Duration of response (DoR)

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

    Measured: From time of response until progression, up to approximately 1 year

  9. Time to response (TTR)

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

    Measured: From first dose until response or progression, up to approximately 1 year.

  10. Median overall survival (mOS)

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

    Measured: From time of first dose until 2 years after end of treatment (Up to approximately 3 years).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jan 2023
  2. Study start29 Mar 2023
  3. Primary completionJan 2026 (estimated)
  4. Study completionFeb 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Phase 1: 3+3 dose escalation Phase2: Expansion cohort
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05705505
Sponsor's protocol ID
19-02
Status last verified
Dec 2023
First submitted
19 Jan 2023
Last updated
12 Dec 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Narazaciclib and Letrozole 2.5mg in people with Endometrioid Endometrial Cancer, run by Traws Pharma, Inc. at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 12 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Victor Moyo, MD (484 535 1402, vmoyo@onconova.us), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicities (DLTs) will be tabulated and summarized by cohort (time frame: From First dose until end of Cycle 1 (28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05705505.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2023.

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