Clinical Trials /

Abemaciclib and Letrozole to Treat Endometrial Cancer

NCT04393285

Description:

This is a phase II single arm trial to evaluate the objective response rate of abemaciclib and letrozole in advanced stage, persistent or recurrent endometrioid endometrial cancer. Treatment will continue until either unacceptable toxicity, progression of disease, or investigator/patient request for withdrawal.

Related Conditions:
  • Endometrial Endometrioid Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Abemaciclib and Letrozole to Treat Endometrial Cancer
  • Official Title: A Phase II Study of Abemaciclib in Combination With Letrozole in Advanced, Recurrent or Metastatic Endometroid Endometrial Cancer

Clinical Trial IDs

  • ORG STUDY ID: GOG-3039
  • NCT ID: NCT04393285

Conditions

  • Endometrial Cancer

Interventions

DrugSynonymsArms
AbemaciclibAbemaciclib and Letrozole
LetrozoleAbemaciclib and Letrozole

Purpose

This is a phase II single arm trial to evaluate the objective response rate of abemaciclib and letrozole in advanced stage, persistent or recurrent endometrioid endometrial cancer. Treatment will continue until either unacceptable toxicity, progression of disease, or investigator/patient request for withdrawal.

Trial Arms

NameTypeDescriptionInterventions
Abemaciclib and LetrozoleExperimentalStudy treatment will consist of abemaciclib 150mg orally twice a day and letrozole 2.5mg orally once a day.
  • Abemaciclib
  • Letrozole

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. 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.

          3. 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.

          4. Prior chemotherapy in the adjuvant setting for Stage I, II, or III is permitted. Prior
             chemoradiotherapy for a pelvic recurrence is permitted.

             Note: No prior chemotherapy in the setting of Stage IV disease is permitted unless the
             patient was without evidence of disease at the completion of chemotherapy and had a
             least six months of progression-free survival since the completion of chemotherapy.

             Regardless of circumstances, no more than one prior chemotherapy regimen (including
             chemo-radiotherapy) is permitted.

             Patients who received prior chemotherapy 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 chemotherapy 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.

          5. Patient must be able to swallow oral medications.

          6. Patient must have an ECOG performance status of 0 to 1.

          7. 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:

               -  Absolute neutrophil count (ANC) greater than or equal to 1500/mcl

               -  Platelets greater than or equal to 100,000 cells/mcl

               -  Hemoglobin greater than or equal to 8 g/dL (Patients may receive erythrocyte
                  transfusions to achieve this hemoglobin level at the discretion of the
                  investigator. Initial treatment must not begin earlier than the day after
                  erythrocyte transfusion).

             Renal function:

             • Creatinine less than or equal to 1.5 x ULN

             Hepatic function:

               -  Bilirubin less than or equal to 1.5 x ULN (Patients with Gilbert's syndrome with
                  a total bilirubin ≤2 times ULN and direct bilirubin within normal limits are
                  permitted).

               -  ALT (alanine aminotransferase) and AST (aspartate aminotransferase) less than or
                  equal to 3 x ULN

               -  Alkaline phosphatase less than or equal to 2.5 x ULN

               -  Albumin greater than or equal to 2.8 g/dL

          8. Patients must have signed an approved informed consent and authorization permitting
             release of personal health information.

          9. Patients must be at least 18 years of age.

         10. Patients of childbearing potential must have a negative urine pregnancy test prior to
             the study entry and be practicing a highly effective form of contraception during the
             study treatment and for 8 weeks after stopping the treatment.

        Highly effective contraception methods include combination of any two of the following:

          1. Use of oral, injected, or implanted hormonal methods of contraception or;

          2. Placement of an intrauterine device (IUD) or intrauterine system (IUS);

          3. Barrier methods of contraception: condom or occlusive cap (diaphgram or cervical/vault
             caps) with spermicidal foam/gel/film/cream/vaginal suppository;

          4. Total abstinence or;

          5. Male/female sterilization. Women are considered post-menopausal and not of
             child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea
             with an appropriate clinical profile (e.g. age appropriate, history of vasomotor
             symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy)
             or tubal ligation at least six weeks prior to randomization. In the case of
             oophorectomy alone, only when the reproductive status of the woman has been confirmed
             by follow up hormone level assessment is she considered not of child-bearing
             potential.

        Exclusion Criteria:

          1. Patients who have previously received any CDK4/6 inhibitor.

          2. Patients with clear cell, serous, carcinosarcoma, mixed histology endometrial cancers,
             or uterine sarcomas.

          3. Known intolerance or hypersensitivity to abemaciclib or letrozole.

          4. Patients who have previously received hormonal therapy for endometrial cancer.

          5. 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.

          6. Patients receiving chronic treatment with systemic steroids or another
             immunosuppressive agent.

          7. Patients with active 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.

          8. 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).

          9. 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.
                  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.

         10. Patients who are pregnant or breast-feeding.

         11. Patients with known central nervous system metastases.

         12. Patients with known human immunodeficiency virus (HIV) infection.

         13. Patients with an impairment of gastrointestinal function or gastrointestinal disease
             that may significantly alter the absorption of abemaciclib (i.e. ulcerative disease;
             uncontrolled nausea, vomiting and/or diarrhea; malabsorption syndrome; clinical signs
             and symptoms of gastrointestinal obstruction; and/or patients who require parenteral
             hydration and/or nutrition).

         14. Patients who plan to receive live attenuated vaccines within 1 week of start of
             abemaciclib and during the study. Patients should also avoid close contact with others
             who have received live attenuated vaccines. Examples of live attenuated vaccines
             include intranasal influenza, measles, mumps, rubella, oral polio, BCG< yellow fever,
             varicella, and TY21a typhoid vaccines.

         15. Patients with active bleeding or pathologic conditions that carry high risk of
             bleeding such as known bleeding disorder or coagulopathy.

         16. Patients with history of unprovoked venous thrombosis unless taking anticoagulation
             treatment for duration of trial.

         17. Patient has a personal history of any of the following conditions: syncope of
             cardiovascular etiology, ventricular arrhythmia of pathologic origin (including but
             not limited to, ventricular tachycardia and ventricular fibrillation), or sudden
             cardiac arrest.

         18. Patients who are currently part of or have participated in any clinical investigation
             with an investigational drug within 30 days prior to dosing.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response Rate
Time Frame:From date of protocol entry to date of first documented response assessed up to 5 years
Safety Issue:
Description:To determine the objective response rate of patients with advanced, persistent, or recurrent endometrioid endometrial cancer

Secondary Outcome Measures

Measure:Time to disease progression
Time Frame:From date of protocol entry to date of first documented progression or death assessed up to 5 years
Safety Issue:
Description:To estimate the time to disease progression
Measure:Toxicity Assessment of Adverse Events
Time Frame:Every 4 weeks assessed up to 5 years
Safety Issue:
Description:To describe the toxicities in patients receiving combination therapy with letrozole and abemaciclib with advanced/metastatic endometrial cancer

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Gynecologic Oncology Group

Last Updated

August 18, 2020