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.
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:
• To determine the objective response rate (ORR)
- 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
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
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
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
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.
1. Prior therapy as described below:
1. Completed last radiotherapy treatment within 14 days prior to first dose of study
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
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.