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A Study to Evaluate Abemaciclib in Advanced Biliary Tract Carcinoma Who Failed Prior First Line Therapy

NCT04003896

Description:

The prognosis of patients with recurrent, late-stage inoperable, or progressed biliary tract carcinoma (BTC) is generally poor. The goal of this clinical study is to determine the effectiveness and safety of abemaciclib in patients with late-stage or progressed BTC that has failed one line of chemotherapy.

Related Conditions:
  • Ampulla of Vater Carcinoma
  • Biliary Tract Carcinoma
  • Extrahepatic Cholangiocarcinoma
  • Gallbladder Carcinoma
  • Intrahepatic Cholangiocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate Abemaciclib in Advanced Biliary Tract Carcinoma Who Failed Prior First Line Therapy
  • Official Title: A Phase II Study to Evaluate the Response and Tolerability of Verzenio (Abemaciclib) in Patients With Advanced Biliary Tract Carcinoma Who Have Failed Prior Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: PSCI-18-052
  • NCT ID: NCT04003896

Conditions

  • Biliary Tract Carcinoma

Interventions

DrugSynonymsArms
AbemaciclibVerzenioAbemaciclib

Purpose

The prognosis of patients with recurrent, late-stage inoperable, or progressed biliary tract carcinoma (BTC) is generally poor. The goal of this clinical study is to determine the effectiveness and safety of abemaciclib in patients with late-stage or progressed BTC that has failed one line of chemotherapy.

Detailed Description

      Biliary Tract Carcinoma (BTC) is a leading cause of cancer-related mortality. The newly
      developed small molecule inhibitor of cyclin-dependent kinases (CDK4 and CDK6), abemaciclib,
      provides a new opportunity of treating patients with BTC. The goal of this clinical study is
      to determine the efficacy and safety of abemaciclib in patients with advanced or metastatic
      BTC that has progressed or intolerant following one line of chemotherapy.

      The investigator's objectives for this study are as follows:

      Primary Objectives:

      • To determine the objective response rate (ORR)

      Secondary Objectives:

        -  To determine progression free survival (PFS)

        -  To determine the disease control rate (DCR)

        -  To determine time to response (TTR)

        -  To determine time to progression (TTP)

        -  To determine time to new metastatic lesion(s) (TTNM)

        -  To determine the overall survival (OS) rate at 6 and 12 months

        -  To determine quality of life (QoL) using EORTC-QLQ-C30 (see Appendix C)

        -  To determine the efficacy and safety of abemaciclib with regard to the subtypes of
           biliary tract carcinoma (BTC) including intrahepatic cholangiocarcinoma (IHCC),
           extra-hepatic cholangiocarcinoma (EHCC), ampullary carcinoma, and gall bladder carcinoma
           (GBC).
    

Trial Arms

NameTypeDescriptionInterventions
AbemaciclibExperimentalAbemaciclib will be given as a single oral agent Approximately up to 27 subjects may be enrolled to attain at least 24 evaluable participants. The starting dose will be 200 mg twice daily. Dosing will continue daily for 28 days, this being one cycle. There will be no protocol scheduled hiatus and daily dosing will be continuous unless there is unacceptable toxicity, disease progression, or death.
  • Abemaciclib

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female, age ≥ 18 years at the time of informed consent.

          2. Capable and willing to sign informed consent form prior to performing any
             protocol-related procedures.

          3. Histologic or cytologic evidence of advanced or metastatic biliary tract cancer,
             including cholangiocarcinoma (intra-hepatic or extra-hepatic bile ducts), ampullary
             carcinoma, or gallbladder carcinoma.

          4. Evidence of recurrent, locally advanced, unresectable, or metastatic disease.

          5. Progressed following or intolerant to one or more lines of systemic therapy

          6. Per the opinion of the physician investigator, predicted life expectancy > 3 months.

          7. Presence of at least 1 lesion that is measurable or evaluable using Response
             Evaluation Criteria in Solid Tumors (RECIST) v1.1.

          8. Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.

          9. Per the opinion of the physician investigator, acute toxicities relating to any prior
             anticancer treatment have improved to Grade 1 or baseline. Exceptions include residual
             alopecia or Grade 2 peripheral neuropathy.

         10. Ability to swallow capsules or tablets.

         11. Adequate organ function as evidenced by the laboratory parameters noted in Section 3.0
             Study Eligibility.

         12. Women of childbearing potential (WOCP) defined as not surgically sterile
             (hysterectomy, tubal ligation, or oophorectomy), or at least 1 year postmenopausal,
             must have a negative serum pregnancy test before study drug administration on cycle 1
             day 1.

         13. WOCP must use a medically acceptable method of contraception and must agree to
             continue used of this method for the duration of the study and for 3 weeks after last
             dose of study drug. Acceptable methods of contraception include abstinence, barrier
             method with spermicide, intrauterine device (IUD) known to have a failure rate of less
             than 1% per year, or steroidal contraceptive (oral, transdermal, implanted, or
             injected) in conjunction with a barrier method.

         14. Male, capable of producing offspring, must use a medical acceptable method of
             contraception and agree to continued use of this method for the duration of the study
             and for 3 weeks after last dose of study drug because of the possible effects on
             spermatogenesis. Acceptable methods of contraception include abstinence, WOCP
             partner's use of barrier method with spermicide, WOCP partner's use of an IUD known to
             have a failure rate of less than 1% per year, WOCP partner's use of steroidal
             contraceptive (oral, transdermal, implanted or injected) or WOCP partner is surgically
             sterile or at least 1 year post-menopausal. In addition, male subjects may not donate
             sperm for the duration of the study and for 30 days after last dose of study drug.

         15. Must be willing and able to comply with the protocol, including adhering to study
             restrictions, remaining at the clinic as required during the study period, and willing
             to return to the clinic for the follow-up evaluation.

        Exclusion Criteria:

          1. Prior therapy as described below:

               1. Completed last radiotherapy treatment within 14 days prior to first dose of study
                  drug.

               2. Completed last dose of myelosuppressive chemotherapy within 21 days prior to
                  first dose of study drug.

               3. Completed last dose of non-myelosuppressive biological or monoclonal antibody
                  therapy within 14 days prior to first dose of study drug.

          2. Ongoing or active infection requiring systemic antibiotics.

          3. History of previous venous thromboembolic events.

          4. Uncontrolled hypertension despite adequate therapy (systolic blood pressure higher
             than 150 mm Hg or diastolic blood pressure higher than 90 mm Hg found on 2 separate
             occasions separated by 1 week).

          5. Diabetes mellitus and occurrence of more than 2 episodes of ketoacidosis in the 12
             months prior to the first dose of study drug.

          6. Active second malignancy other than curatively resected basal cell carcinoma of the
             skin, squamous cell carcinoma of the skin, in situ carcinoma of the cervix, or other
             cancers treated with curative intent, and no known active disease in the 3 years prior
             to enrollment.

          7. Primary brain tumor or brain metastases from another primary site.

          8. Known history of human immunodeficiency virus (HIV).

          9. Known active viral hepatitis B or viral hepatitis C.

         10. 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.
             Subjects with controlled atrial fibrillation for more than 30 days are permitted.

         11. Congestive heart failure (New York Heart Association [NYHA] Class III or IV), or acute
             coronary syndromes within 6 months of enrollment.

         12. Female subjects who are pregnant or breastfeeding.

         13. Any other medical, psychiatric, or social condition, which in the opinion of the
             physician investigator, would preclude participation in the study, pose an undue
             medical hazard, interfere with the conduct of the study, or interfere with
             interpretation of the study results. For example, interstitial lung disease, severe
             dyspnea at rest or requiring oxygen therapy.

         14. Use of an investigational drug within 1 month before the screening visit or currently
             participating in another investigational study.

         15. Any disorder that may interfere with drug absorption, distribution, metabolism, or
             excretion (including gastrointestinal or bariatric surgery, preexisting Crohn's
             Disease or ulcerative colitis, or preexisting condition resulting in baseline Grade 2
             or higher diarrhea).

         16. Known hypersensitivity to any of the components in abemaciclib including
             micro-crystalline cellulose 102, microcrystalline cellulose 101, lactose monohydrate,
             croscarmellose sodium, sodium stearyl fumarate, silicon dioxide. Color mixture
             ingredients—polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, iron oxide
             yellow, and iron oxide red.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:objective response rate
Time Frame:approximately 7 months
Safety Issue:
Description:ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 at the beginning of cycle 3, 5, 7 (each cycle is 28 days).

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:3 years
Safety Issue:
Description:the time interval from date of first dose of study drug to first documented disease progression or death from any cause, whichever occurs first.
Measure:disease control rate
Time Frame:approximately 7 months
Safety Issue:
Description:tThe number of subjects achieving a response (complete response, partial response, stable disease) at the beginning of cycle 3, 5, 7 (each cycle is 28 days).
Measure:time to response
Time Frame:approximately 7 months
Safety Issue:
Description:the time interval from date of first dose to first documented response (complete response, CR or partial response, PR) at the beginning of cycle 3, 5, 7 (each cycle is 28 days).
Measure:time to progression
Time Frame:3 years
Safety Issue:
Description:the time interval from date of first dose of study drug to first documented disease progression.
Measure:time to new metastatic lesion(s)
Time Frame:3 years
Safety Issue:
Description:the time interval from the date of the first dose of study drug to the first documented new metastatic lesion not reported at baseline.
Measure:overall survival rate
Time Frame:up to 12 months
Safety Issue:
Description:the proportion of subjects who are alive at 6 months and 12 months from the date of first dose of study drug, respectively.
Measure:quality of life questionaire
Time Frame:approximately 8 months
Safety Issue:
Description:from the date of baseline and then every 4 weeks using the EORTC-QLQ-C30 at the end of cycle 1,2,3,4,5,6,7,8 (each cycle is 28 days).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Milton S. Hershey Medical Center

Trial Keywords

  • Biliary Tract Carcinoma
  • Abemaciclib

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