Clinical Trial - NCT03675893

Abemaciclib With Letrozole in Recurrent or Persistent Endometrial Cancer

Recruiting

Sponsor: Dana-Farber Cancer Institute

Collaborators: Eli Lilly and Company

Information provided by (Responsible party): Principal Investigator Dana-Farber Cancer Institute Panagiotis Konstantinopoulos, MD, PhD Principal Investigator

ClinicalTrials.gov Identifier: NCT03675893

Protocol Info

Short Description: LY3023414 + Abemaciclib +/- Letrozole in Endometrial Cancer
Long Description: A Phase 2 Two-Group Study of LY3023414 and Abemaciclib with or without Letrozole in Recurrent or Persistent Endometrial Cancer
MGH Status: Open
Sponsor: DF/HCC
Disease Program: GYN

Next Steps


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Purpose

This research study is studying a combination of targeted therapies as a possible treatment for estrogen-receptor positive (ER+) endometrial cancer. The drugs involved in this study are: - Abemaciclib (also known as Verzenio™) - Letrozole (also known as Femara®)
Condition Title Intervention Phase
Endometrial Cancer Letrozole Abemaciclib Phase 2
Study Type Interventional
Official Title A Phase 2 Study of Abemaciclib With Letrozole in Recurrent or Persistent Endometrial Cancer

Primary Outcome Measures

Progression Free Survival Rate [Time Frame: 6 months] [Designated as safety issue: ]

Objective Tumor Response Rate [Time Frame: 6 months] [Designated as safety issue: ]


Secondary Outcome Measures

Overall Survival Rate [Time Frame: 3 years] [Designated as safety issue: ]

Treatment-related toxicities [Time Frame: 3 years] [Designated as safety issue: ]

Estimated Enrollment: 40
Study Start Date: December 2018
Estimated Study Completion Date: May 2024
Estimated Primary Completion Date: May 2021
Arms Assigned Interventions

Experimental:Cohort 1A

Abemaciclib is administered by mouth twice daily Letrozole is administered by mouth once daily
Drug:Abemaciclib
Abemaciclib is a cyclin-dependent kinase (CDK) inhibitor.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: Female

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • Participants must have cytologically or histologically confirmed endometrial cancer that is recurrent or metastatic and/or resistant to standard therapies, or for which no standard therapy is available.
  • Participants must have ER-positive disease, defined as ≥ 1 percent of tumor cell nuclei being immunoreactive by immunohistochemistry (IHC). If multiple analyses have been performed, judgment should be based on the most recent biopsy or pathology specimen analyzed in a CLIA-certified laboratory.
  • Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam.
  • Age ≥ 18 years
  • ECOG performance status of 0 or 1
  • Participants must have normal organ and bone marrow function as defined below:
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelets ≥ 100,000/mcL
  • Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN, OR
  • 5 × institutional ULN if liver metastases are present
  • Creatinine ≤ 1.5 × institutional ULN, OR
  • Creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
  • The effects of the study agents on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use a medically approved contraceptive method during the treatment period and for 3 months following the last dose of study agent. Contraceptive methods may include an intrauterine device (IUD) or barrier method. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. A negative serum pregnancy test is required for study entry from women of childbearing potential.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Ability to swallow and retain oral medication.
  • Participants must have archival tissue available for analysis in the form of a formalin-fixed paraffin embedded (FFPE) block or unstained slides. Note: confirmation of availability of archival tissue is the only requirement for eligibility, archival tissue does not need to be received by the study team prior to enrollment

Exclusion Criteria:

  • Participants who have had chemotherapy, immune therapy, other investigational therapy, or major surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to the first dose of study medication. Previous hormonal therapy, including prior letrozole, is allowed and there is no required washout period for hormonal therapy.
  • Participants who have had tyrosine kinase inhibitor (TKI) therapy within 5 half-lives of study entry.
  • Participants who have had radiation therapy within 2 weeks of the first dose of study medication.
  • Participants who have received previous treatment with CDK4/6 inhibitors, including but not limited to previous abemaciclib therapy.
  • Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agents that the participant will be administered.
  • Participants who at the time of study enrollment are known to require concomitant therapy with moderate or strong CYP3A4 inducers, or strong inhibitors of CYP3A4. Due to potential drug interactions, concomitant use of these medications is not permitted for the duration of treatment on trial. Participants are eligible for study entry if an appropriate substitution is made prior to the first dose of study medication.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Participants with histories or evidence of cardiovascular risk including any of the following: acute coronary syndromes (i.e. myocardial infarction or angina), coronary angioplasty, or stenting within 6 months prior to study enrollment.
  • Pregnant women are excluded from this study because the study agents are anti-cancer agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study agents, breastfeeding must be discontinued if the mother is treated on trial.
  • Individuals with a history of a different malignancy are ineligible with the following exceptions: individuals who have been treated and are disease-free for a minimum of 5 years prior to study enrollment, or individuals who are deemed by the treating investigator to be at low risk for disease recurrence. Additionally, individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: basal or squamous cell carcinomas of the skin, and breast or cervical carcinomas in situ.
  • Known HIV-positive participants are ineligible because of the increased risk of lethal infections when treated with marrow-suppressive therapy.
  • Participants with a history of atrial fibrillation or atrial flutter.
  • Participants with a history of uncontrolled hypertension despite optimal medical management, defined as systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03675893

Locations

  • United States, Massachusetts
    • Massachusetts General Hospital Cancer Center Boston, Massachusetts, United States, 02214
    • Beth Israel Deaconess Medical Center (BIDMC) Boston, Massachusetts, United States, 02215
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Dana-Farber Cancer Institute

Eli Lilly and Company

More Information

No publications provided

Responsible Party: Principal Investigator Dana-Farber Cancer Institute Panagiotis Konstantinopoulos, MD, PhD Principal Investigator
ClinicalTrials.gov Identifier: NCT03675893
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Dana-Farber Cancer Institute:

Endometrial Cancer

CDK4/6

ER+

Estrogen Receptor

Additional relevant MeSH terms:

Endometrial Neoplasms

Letrozole

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on September 03, 2020