Abemaciclib and Letrozole to Treat Endometrial Cancer

NCT04393285 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: GOG-3039
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 29

Brief Summary

This is a phase II single arm trial to determine the percentage of patients without evidence of disease progression on abemaciclib and letrozole in advanced stage, persistent or recurrent endometrioid endometrial cancer at 6 months. Treatment will continue until either unacceptable toxicity, progression of disease, or investigator/patient request for withdrawal.

Conditions

Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  To evaluate the efficacy in terms of the probability of surviving progression free for at least 6 months (PFS at 6 mo)

  From date of protocol entry to date of first documented progression up to 6 months

Secondary Outcomes (3)

• Response rate

  From date of protocol entry to date of first response assessed up to 5 years

• Time to disease progression or death

  From date of protocol entry to date of progression or death assessed up to 5 years

• Toxicity Assessment of Adverse Events

  Every 4 weeks assessed up to 5 years

Other Outcomes (6)

• Protein expression analysis of Cyclin D and E Pathway

  At time of primary and secondary outcome analysis up to 5 years

• Protein expression analysis of Immune Cell Infiltration and activity

  At time of primary and secondary outcome analysis up to 5 years

• Protein expression analysis of sex hormone/insulin/IGF pathway

  At time of primary and secondary outcome analysis up to 5 years

Study Arms (1)

Abemaciclib and Letrozole

EXPERIMENTAL

Study treatment will consist of abemaciclib 150mg orally twice a day and letrozole 2.5mg orally once a day.

Drug: Abemaciclib; Drug: Letrozole

Interventions

Letrozole DRUG

Letrozole 2.5mg orally once a day

Abemaciclib and Letrozole

Abemaciclib DRUG

Abemaciclib 150mg orally twice a day

Abemaciclib and Letrozole

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have advanced (FIGO 2014 Stage III or IV), persistent, or recurrent endometrial carcinoma, which is not likely to be curable by surgery or radiotherapy. Histologic confirmation of recurrent disease is required. For cases of persistent disease, histologic confirmation of the primary disease with radiologic evidence of progression is required.
• Patients must have endometrioid histology (all grades allowed) based on hysterectomy or biopsy specimen (Hormone receptor status is not required for enrollment).
• Sites are required to report results of previous MMR, MSI, and ER/PR status testing in Medidata Rave if available.
• All patients must have measurable disease. Measurable disease is defined by RECIST version 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be greater than or equal to 10mm when measured by CT, MRI or caliper measurement by clinical exam; or greater than or equal to 20mm when measured by chest x-ray. Lymph nodes must be greater than or equal to 15mm in short axis when measured by CT or MRI.
• Patient must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
• Prior chemotherapy in the adjuvant setting for Stage I, II, or III is permitted. Prior chemoradiotherapy for a pelvic recurrence is permitted.
• Note: Chemotherapy in the setting of Stage IV disease is permitted but the patient must be without evidence of disease at the completion of chemotherapy and have at least six months of progression-free survival since the completion of chemotherapy before detection of the recurrent cancer for which she is receiving treatment on this protocol.
• Prior immunotherapy and/or targeted therapy is allowed in addition to, in combination with, in lieu of, or subsequent to prior chemotherapy.
• Regardless of circumstances, no more than one prior chemotherapy regimen (including chemo-radiotherapy) is permitted, and no more than one additional systemic therapy is permitted. Hence, eligible patient may have received 0, 1, or 2 prior lines of systemic therapy and for women who received two prior lines of therapy, only one of them may have included chemotherapy.
• Patients who received prior chemotherapy, immunotherapy or targeted therapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to enrollment. A washout period of at least 21 days is required between last systemic therapy dose and initiation of therapy.
• Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and initiation of therapy.
• Patient must be able to swallow oral medications.
• Patient must have an ECOG performance status of 0 to 1.
• Patients must have adequate organ and marrow function as defined below NOTE: Institutional/laboratory upper limit of normal = ULN Institutional/laboratory lower limit of normal = LLN
• Bone marrow function:

You may not qualify if:

• Patients who have previously received any CDK4/6 inhibitor.
• Patients with clear cell, serous, carcinosarcoma, mixed histology endometrial cancers, or uterine sarcomas.
• Known intolerance or hypersensitivity to abemaciclib or letrozole.
• Patients who have previously received hormonal therapy for endometrial cancer.
• Patients with concomitant invasive malignancy or a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the past five years. Patients are also excluded if their previous cancer treatment contraindicates this protocol.
• Patients receiving chronic treatment with systemic steroids or another immunosuppressive agent.
• Patients with active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment, fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]). Screening is not required for enrollment.
• Patients with a serious pre-existing medical condition(s) that would preclude participation in this study (for example: interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment (i.e. estimated creatinine clearance \<30ml/min), history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or pre-existing chronic condition resulting in baseline grade 2 or higher diarrhea).
• Patients with a known history of cardiac disease. This includes:
• Uncontrolled hypertension, defined as systolic greater than 150mm Hg or diastolic greater than 90mm Hg despite antihypertensive medications
• Myocardial infarction or unstable angina within 6 months prior to registration.
• New York Heart Association (NYHA) Class II or greater congestive heart failure.
• History of serious ventricular arrhythmia (i.e. ventricular tachycardia or ventricular fibrillation) or serious cardiac arrhythmia requiring medication, syncope of cardiovascular etiology or sudden cardiac arrest. This does not include asymptomatic atrial fibrillation with controlled ventricular rate.
• Cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6 months prior to the first date of study therapy.
• Patients who are pregnant or breast-feeding.

Sponsors & Collaborators

• Eli Lilly and Company: collaborator
• Gynecologic Oncology Group: lead

Study Sites (29)

University of South Alabama Mitchell Cancer Center

Mobile, Alabama, 36604, United States

Location

Alaska Women's Cancer Care

Anchorage, Alaska, 99508, United States

Location

Smillow Cancer Care at Greenwich

Greenwich, Connecticut, 06830, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Sylvester Comprehensive Cancer Center-Lennar Foundation Medical Center

Coral Gables, Florida, 33146, United States

Location

Sylevester Comprehensive Cancer Center-Deerfield Beach

Deerfield Beach, Florida, 33442, United States

Location

UF Health Cancer Center

Gainesville, Florida, 32160, United States

Location

University of Miami - Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

UT Health Tower

Miami, Florida, 33136, United States

Location

Advent Health - Orlando

Orlando, Florida, 32804, United States

Location

Sylvester Comprehensive Cancer Center-Plantation

Plantation, Florida, 33324, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Lewis Cancer & Research Pavilion

Savannah, Georgia, 31405, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Baptist Healthcare System

Lexington, Kentucky, 40503, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

University of Massachusetts

Worcester, Massachusetts, 01605, United States

Location

St. Joseph Mercy Hospital

Ann Arbor, Michigan, 48106, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Holy Name Medical Center

Teaneck, New Jersey, 07666, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Oklahoma Cancer Specialists and Research Institute

Tulsa, Oklahoma, 74146, United States

Location

Reading Hospital-McGlinn Cancer Institute

Reading, Pennsylvania, 19611, United States

Location

Abington Memorial Hospital

Willow Grove, Pennsylvania, 19090, United States

Location

Baptist Health Center Lexington

Salt Lake City, Utah, 84112, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

abemaciclib; Letrozole

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Marilyn Huang, MD

  University of Virginia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2020
• First Posted: May 19, 2020
• Study Start: October 10, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 9, 2026

Record last verified: 2026-03

Locations

US (29)