Clinical Trials /

Abemaciclib for the Treatment of Recurrent Ovarian or Endometrial Cancer

NCT04469764

Description:

This phase II trial studies how well abemaciclib works in treating patients with ovarian or endometrial cancer that has an activation of the CDK4/6 pathway and that has come back (recurrent). Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving abemaciclib may work better for the treatment of recurrent ovarian and endometrial cancer.

Related Conditions:
  • Endometrial Endometrioid Adenocarcinoma
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Ovarian Epithelial Tumor
  • Primary Peritoneal Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Abemaciclib for the Treatment of Recurrent Ovarian or Endometrial Cancer
  • Official Title: An Open Label Phase II Study of the Efficacy and Safety of Abemaciclib, a Cyclin Dependent Kinase (CDK4/6) Inhibitor in Selected Patients With Recurrent Ovarian or Endometrial Cancer

Clinical Trial IDs

  • ORG STUDY ID: 20-000769
  • SECONDARY ID: NCI-2020-04544
  • SECONDARY ID: 20-000769
  • NCT ID: NCT04469764

Conditions

  • Recurrent Endometrial Carcinoma
  • Recurrent Fallopian Tube Carcinoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Primary Peritoneal Carcinoma

Interventions

DrugSynonymsArms
AbemaciclibLY-2835219, LY2835219, VerzenioTreatment (abemaciclib)
AnastrozoleAnastrazole, Arimidex, ICI D1033, ICI-D1033, ZD-1033Treatment (abemaciclib)
LetrozoleCGS 20267, FemaraTreatment (abemaciclib)

Purpose

This phase II trial studies how well abemaciclib works in treating patients with ovarian or endometrial cancer that has an activation of the CDK4/6 pathway and that has come back (recurrent). Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving abemaciclib may work better for the treatment of recurrent ovarian and endometrial cancer.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To obtain an estimate of the proportion of patients' progression-free at 16 weeks (16 week
      progression free survival [PFS] rate) in patients with recurrent ovarian (including fallopian
      tube and primary peritoneal) or recurrent endometrial cancer following treatment with
      abemaciclib as a molecularly matched targeted therapy.

      SECONDARY OBJECTIVE:

      I. To assess objective response rate (ORR) as per Response Evaluation Criteria in Solid
      Tumors (RECIST), progression free survival (PFS) and safety following treatment with
      abemaciclib as a molecularly matched targeted therapy.

      EXPLORATORY OBJECTIVES:

      I. To explore the relationship between response to abemaciclib and somatic gene alterations
      that lead to CDK4/6 activation in ovarian cancer.

      II. To explore the relationship between response to abemaciclib and hormone receptor
      expression levels as well as somatic gene alterations that lead to CDK4/6 activation in
      endometrial cancer.

      OUTLINE:

      Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28. Patients with tumors
      that are hormone receptor positive also receive anastrozole or letrozole per standard of
      care. Cycles repeat every 28 days in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up for 30 days, and then every 12
      weeks up to 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (abemaciclib)ExperimentalPatients receive abemaciclib PO BID on days 1-28. Patients with tumors that are hormone receptor positive also receive and anastrozole or letrozole per standard of care. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Abemaciclib
  • Anastrozole
  • Letrozole

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically-confirmed ovarian epithelial (including fallopian tube and primary
             peritoneal) cancer or endometrial cancer

          -  Molecular tumor board confirms that patient's archival ovarian cancer tumor specimen
             has been assessed using standard of care genomic profiling and demonstrates CDK4/6
             activation features

          -  Molecular tumor board confirms that patient's archival endometrial cancer tumor
             specimen has been assessed using standard of care genomic profiling and is of
             endometrioid histology, has positive hormone receptor expression and lack of Cyclin E
             gene (CCNE) amplification or retinoblastoma susceptibility gene product (RB) loss

          -  At least one prior chemotherapy regimen for the treatment of recurrent ovarian or
             endometrial cancer

          -  Patients who received 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 study
             initiation

          -  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 study initiation

          -  The patient is able to swallow oral medications

          -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          -  Patient must be willing and able to comply with scheduled visits, treatment plans,
             laboratory tests, and other study procedures

          -  Informed consent must be obtained in writing for all patients prior to performing
             study/screening procedures and prior to registration into the study

          -  Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

          -  Platelets >= 100 x 10^9/L

          -  Hemoglobin >= 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 the erythrocyte transfusion

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN). Patients with Gilbert's syndrome
             with a total bilirubin =< 2.0 times ULN and direct bilirubin within normal limits are
             permitted

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN

          -  Female participants of childbearing potential must have a negative serum pregnancy
             test within 7 days of the first dose of abemaciclib and agree to use a highly
             effective contraception method during the treatment period and for 3 weeks following
             the last dose of abemaciclib

        Exclusion Criteria:

          -  Anticipation of immediate need for a major surgical procedure (e.g., impending bowel
             obstruction, gastrointestinal perforation) or radiation therapy during the trial

          -  Diagnosis of any second malignancy within the last 5 years, except for adequately
             treated basal cell or squamous cell skin cancer, or for in situ carcinoma of the
             cervix uteri or breast

          -  Treatment with chemotherapy, surgery, blood products, or an investigational agent
             within 3 weeks of trial enrollment

          -  Any of the following within 6 months prior to trial registration: myocardial
             infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft,
             New York Heart Association (NYHA) class III or IV congestive heart failure,
             cerebrovascular accident or transient ischemic attack, pulmonary embolism

          -  Unstable brain metastases or carcinomatous meningitis

          -  Patient of child-bearing potential is evidently pregnant or is breast feeding. A woman
             with child bearing potential is defined as not surgically sterile or being
             post-menopausal for less than 6 months

          -  Patient of child-bearing potential is not willing to use adequate contraceptive
             precautions. Adequate effective method of contraception are those which result in low
             failure rates, less than 1% per year, such as non-hormonal intrauterine device (IUD),
             condoms, sexual abstinence or vasectomized partner

          -  The patient has serious preexisting medical condition(s) that would preclude
             participation in this study (for example, interstitial lung disease, severe dyspnea at
             rest or requiring oxygen therapy, history of major surgical resection involving the
             stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a
             preexisting chronic condition resulting in baseline grade 2 or higher diarrhea)

          -  The patient has 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

          -  The patient has a personal history of any of the following conditions: syncope of
             cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but
             not limited to, ventricular tachycardia and ventricular fibrillation), or sudden
             cardiac arrest

          -  Current use or anticipated need for: Food or drugs that are known strong CYP3A4
             inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole,
             posaconazole, erythromycin, clarithromycin, tilithromycin, indinavir, saquinavir,
             ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone,
             diltiazem, and delaviridine)

          -  Other severe acute or chronic medical or psychiatric condition, or significant
             laboratory abnormality requiring further investigation that may cause undue risk for
             the patient's safety, inhibit protocol participation, or interfere with interpretation
             of trial results, and in the judgment of the investigator would make the patient
             inappropriate for entry into this trial
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of patients who are progression-free
Time Frame:At 16 weeks
Safety Issue:
Description:Will be calculated with corresponding 95% unadjusted exact binomial confidence interval (CI).

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to 1 year
Safety Issue:
Description:Assessed per Response Evaluation Criteria in Solid Tumors (RECIST).
Measure:Progression free survival (PFS)
Time Frame:Time from registration until date of progression or death, assessed up to 1 year
Safety Issue:
Description:Date of progression will be defined as the date of the first imaging or clinical exam or biochemical occurrence showing disease progression. PFS will be calculated with corresponding 95% unadjusted exact binomial confidence interval. Kaplan-Meier estimates and Kaplan Meier plots of this endpoint will be produced. Two-sided 95% confidence intervals will accompany the Kaplan-Meier estimate of the median.
Measure:Incidence of adverse events
Time Frame:At 16 weeks and up to 90 days after completion of treatment
Safety Issue:
Description:To assess safety
Measure:Clinical benefit rate
Time Frame:Up to 1 year after completion of treatment
Safety Issue:
Description:Defined as achieving a confirmed objective response (complete response [CR] or partial response [PR]) or achieving stable disease for a minimum duration of 4 months, will be provided with the exact two-sided 95% confidence interval.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Jonsson Comprehensive Cancer Center

Last Updated

July 21, 2020