Clinical Trials /

Abemaciclib in Metastatic or Locally Advanced Anaplastic/Undifferentiated Thyroid Cancer

NCT04552769

Description:

The purpose of the study is to evaluate the efficacy of treatment with abemaciclib in patients with anaplastic thyroid/undifferentiated thyroid

Related Conditions:
  • Thyroid Gland Undifferentiated (Anaplastic) Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Abemaciclib in Metastatic or Locally Advanced Anaplastic/Undifferentiated Thyroid Cancer
  • Official Title: Abemaciclib in Metastatic or Locally Advanced Anaplastic/Undifferentiated Thyroid Cancer

Clinical Trial IDs

  • ORG STUDY ID: IRB-57905
  • SECONDARY ID: END0023
  • NCT ID: NCT04552769

Conditions

  • Thyroid Cancer
  • Anaplastic Thyroid Cancer
  • Undifferentiated Thyroid Cancer

Interventions

DrugSynonymsArms
AbemaciclibVerzenio, LY2835219, 2-pyrimidinamine, N-(5-((4-ethyl-1-piperazinyl)methyl)-2-pyridinyl)-5-fluoro-4-(4-fluoro-2-methyl-1-(1-methylethyl)-1H-benzimidazol-6-yl)Abemaciclib

Purpose

The purpose of the study is to evaluate the efficacy of treatment with abemaciclib in patients with anaplastic thyroid/undifferentiated thyroid

Detailed Description

      Primary Objective The primary objective is to determine the overall response rate after
      treatment with abemaciclib in patients with anaplastic thyroid/undifferentiated thyroid
      cancer.

      Secondary Objectives The secondary objectives are to describe the overall survival (OS) and
      progression-free survival (PFS) after treatment with abemaciclib in patients with anaplastic
      thyroid/undifferentiated thyroid cancer.Safety assessments of AE's will also be analysed
    

Trial Arms

NameTypeDescriptionInterventions
AbemaciclibExperimentalEach cycle of therapy will be 28 days long. A completed cycle will be twice daily abemaciclib. Number of Cycles: until progression or unacceptable toxicity develops
  • Abemaciclib

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically confirmed diagnosis of anaplastic thyroid cancer or
             undifferentiated thyroid cancer that does not have a known BRAF V600E positive on
             tissue/blood testing. BRAF V600E positive patients are eligible if they have
             previously received FDA approved therapy for this genetic abnormality and progressed
             or become intolerant.

          2. Patients will be eligible if they meet either criteria:

               -  Unresectable anaplastic thyroid cancer limited to the neck: Patients must have
                  received radiation therapy or surgery to primary tumor and have subsequent
                  evidence of anaplastic thyroid cancer (ATC).

               -  Metastatic anaplastic thyroid cancer: either with entirely surgically removed
                  cancer/metastatic only disease, or with disease in the neck not requiring
                  radiation or surgery to the neck mass.

          3. Patients with a bulky thyroid/neck mass and those in whom airway obstruction is
             suspected should undergo an evaluation via indirect or direct laryngoscopy to ensure
             patency of the trachea/airway prior to enrollment

          4. Patients will not have any other curative therapeutic option, such as radiation or
             surgery.

          5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

          6. Have measurable disease based on RECIST 1.1

          7. Be willing to provide tissue from a newly obtained core or excisional biopsy of a
             tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days)
             prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples
             cannot be provided (e.g. inaccessible or subject safety concern) may submit an
             archived sample.

          8. Be ≥ 18 years of age on day of signing informed consent.

          9. 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 study treatment start. A
             washout period of at least 21 days is required between last chemotherapy dose and
             study treatment start (provided the patient did not receive radiotherapy).

         10. 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 treatment start.

         11. The patient is able to swallow oral medications.

         12. The patient has adequate organ function for all of the following criteria, Laboratory
             Value Guidance to Establish Adequate Organ Function System Laboratory Value
             Hematologic absolute neutrophil count (ANC)≥1.5 × 109/L Platelets≥100 × 109/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.

             Hepatic Total bilirubin ≤1.5 × 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 × ULN

         13. Women of childbearing potential and all men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) while taking drug and agree
             to continue for 3 months after the last dose of study treatment. Women of child
             bearing potential and male patients for 3 months should not mother or father a child
             in this period. A condom is required to be used also by vasectomized men in order to
             prevent delivery of the drug via seminal fluid.

         14. Patient has the ability to understand and provide signed informed consent.

         15. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
             tests and other procedures.

        Exclusion Criteria:

          1. Patients with known hypersensitivity to any of the excipients of abemaciclib

          2. History of carcinomatous meningitis

          3. Prior therapy with abemaciclib.

          4. The patient has serious and/or uncontrolled preexisting medical condition(s) that, in
             the judgment of the investigator, would preclude participation in this study (for
             example, interstitial lung disease, severe dyspnea at rest or requiring oxygen
             therapy, severe renal impairment [e.g. 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 a preexisting chronic condition
             resulting in baseline Grade 2 or higher diarrhea).

          5. Females who are pregnant or lactating.

          6. The patient has 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.

          7. 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.

          8. Presence or history of a malignant disease other than thyroid cancer that has been
             diagnosed and/or required therapy within the past year and is undergoing active
             anticancer treatment. Exceptions to this exclusion include the following: completely
             resected basal cell and squamous cell skin cancers, and completely resected carcinoma
             in situ of any type.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response (OR)
Time Frame:8 (+/-4) weeks from start of treatment
Safety Issue:
Description:Overall response defined as either complete response or partial response assessed using RECIST v1.1 criteria. This measure will be reported as a number without dispersion. RECIST v1.1 criteria: Evaluation of Target Lesions Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, no appearance of new lesions. Evaluation of Non-Target Lesions Complete Response (CR): Disappearance of all non-target lesions Incomplete Response/Stable Disease (SD): Persistence of one or more non-target lesion(s) Progressive Disease (PD): Appearance of one or more new lesions

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:3 years
Safety Issue:
Description:Overall survival defined as duration of time from start of treatment to death from any cause. This will be reported as median survival time with interquartile range
Measure:Progression-free survival (PFS)
Time Frame:3 years
Safety Issue:
Description:Progression-free survival (PFS) defined as the duration of time from start of treatment to time of progression or death from any cause. This will be reported as median time with interquartile range.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Stanford University

Last Updated

September 11, 2020