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Trial record 1 of 1 for:    NCT04393285
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Abemaciclib and Letrozole to Treat Endometrial Cancer

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ClinicalTrials.gov Identifier: NCT04393285
Recruitment Status : Recruiting
First Posted : May 19, 2020
Last Update Posted : May 12, 2021
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
GOG Foundation ( Gynecologic Oncology Group )

Tracking Information
First Submitted Date  ICMJE May 11, 2020
First Posted Date  ICMJE May 19, 2020
Last Update Posted Date May 12, 2021
Actual Study Start Date  ICMJE October 10, 2020
Estimated Primary Completion Date June 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 13, 2020)
Response Rate [ Time Frame: From date of protocol entry to date of first documented response assessed up to 5 years ]
To determine the objective response rate of patients with advanced, persistent, or recurrent endometrioid endometrial cancer
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2020)
  • Time to disease progression [ Time Frame: From date of protocol entry to date of first documented progression or death assessed up to 5 years ]
    To estimate the time to disease progression
  • Toxicity Assessment of Adverse Events [ Time Frame: Every 4 weeks assessed up to 5 years ]
    To describe the toxicities in patients receiving combination therapy with letrozole and abemaciclib with advanced/metastatic endometrial cancer
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 13, 2020)
  • Protein expression analysis of Cyclin D and E Pathway [ Time Frame: At time of primary and secondary outcome analysis up to 5 years ]
    Perform multiplexed protein expression analysis at a single cell level using imaging mass cytometry (IMC), exploring the relationship to response, and assessing for longitudinal changes upon progression/relapse. Cyclin D and E Pathway: Protein expression of CCND1, CDK4, CDK6, RB1, phospho-RB1, CDKN2A, CCNE1, CCNE2, CDK2, CCND3
  • Protein expression analysis of Immune Cell Infiltration and activity [ Time Frame: At time of primary and secondary outcome analysis up to 5 years ]
    Perform multiplexed protein expression analysis at a single cell level using imaging mass cytometry (IMC), exploring the relationship to response, and assessing for longitudinal changes upon progression/relapse. Immune cell infiltration and activity: CD45, CD3, CD8, CD4, FoxP3, PD-1, Tim-3, CTLA-4, CD25, Ki67.
  • Protein expression analysis of sex hormone/insulin/IGF pathway [ Time Frame: At time of primary and secondary outcome analysis up to 5 years ]
    Perform multiplexed protein expression analysis at a single cell level using imaging mass cytometry (IMC), exploring the relationship to response, and assessing for longitudinal changes upon progression/relapse. Sex hormone/insulin/IGF pathway: Protein expression of ER (ESR1), PR, IR, IGF1R, and phospho-IGF1R/IR
  • Cyclin D1 3'UTR mutations [ Time Frame: At time of primary and secondary outcome analysis up to 5 years ]
    Determine the frequency of Cyclin D1 3'UTR mutations and correlatioin with response.
  • Estradiol levels [ Time Frame: At time of primary and secondary outcome analysis up to 5 years ]
    Compare the pre- and post-treatment circulating estradiol levels, and association with response.
  • Insulin levels [ Time Frame: At time of primary and secondary outcome analysis up to 5 years ]
    Compare the pre- and post-treatment circulating insulin levels, and association with response.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Abemaciclib and Letrozole to Treat Endometrial Cancer
Official Title  ICMJE A Phase II Study of Abemaciclib in Combination With Letrozole in Advanced, Recurrent or Metastatic Endometroid Endometrial Cancer
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Endometrial Cancer
Intervention  ICMJE
  • Drug: Abemaciclib
    Abemaciclib 150mg orally twice a day
  • Drug: Letrozole
    Letrozole 2.5mg orally once a day
Study Arms  ICMJE Experimental: Abemaciclib and Letrozole
Study treatment will consist of abemaciclib 150mg orally twice a day and letrozole 2.5mg orally once a day.
Interventions:
  • Drug: Abemaciclib
  • Drug: Letrozole
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 13, 2020)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 1, 2023
Estimated Primary Completion Date June 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jennifer Klein, MEd 2158540770 jklein@gog.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04393285
Other Study ID Numbers  ICMJE GOG-3039
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GOG Foundation ( Gynecologic Oncology Group )
Study Sponsor  ICMJE Gynecologic Oncology Group
Collaborators  ICMJE Eli Lilly and Company
Investigators  ICMJE
Study Chair: Marilyn Huang, MD University of Miami
PRS Account GOG Foundation
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP