Phase II Trial of Dasatinib in Patients With Isocitrate Dehydrogenase (IDH)-Mutant Advanced Intrahepatic Cholangiocarcinoma

Inclusion Criteria

• Participants must meet the following criteria on screening examination to be eligible to participate in the study:
• Participants must have unresectable or metastatic histologically confirmed intrahepatic cholangiocarcinoma
• Patients must have either IDH1 or IDH2 mutations (any known mutations) based on the SNaPshot platform or other molecular testing platform from either archived tissue or fresh biopsy (tested in CLIA-certified lab)
• Patients with other biliary tract cancers (extrahepatic or gallbladder cancers) with IDH1 or IDH2 mutations are allowed
• 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) as ≥ 20 mm with conventional techniques or as ≥10 mm with spiral CT scan. See section 10 for the evaluation of measureable disease.
• Participants must have received at least one prior platinum-based regimen for advanced cholangiocarcinoma and had progressive disease or become intolerable to the regimen
• Age ≥18 years.
• Life expectancy of ≥3 months.
• ECOG performance status 0 or 1 (see Appendix A).
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1,200/mcL
• Platelets ≥75,000/mcL
• Hemoglobin ≥9 g/dL
• Total bilirubin ≤ 2.5 x the upper limit of normal
• AST (SGOT)/ALT (SGPT) ≤ 5 X institutional upper limit of normal
• PT/PTT ≤ 1.5 x ULN
• Creatinine ≤ 1.5 or GFR ≥ 60 mL/min/1.73m2
• Serum Albumin ≥2.8 g/dl
• Prior chemoembolization, radiofrequency ablation, or radiation to the liver is allowed as long as the patient has measurable disease outside of the treated area or measurable progression at the site of the treated area
• Ability to understand and the willingness to sign a written informed consent document.
• Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (eg, male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s).
• Women of childbearing potential must have a negative pregnancy test at screening. Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Postmenopause is defined as amenorrhea ≥ 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason.

Exclusion Criteria

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
• Prior treatment with dasatinib
• Periampullary tumors
• Chemotherapy, within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin) or those who have not recovered to less than or equal to grade 1 from adverse events due to agents administered more than 4 weeks earlier.
• The subject has received radiation therapy:
• to bone or brain metastasis within 14 days of the first dose of study treatment
• to any other site(s) within 28 days of the first dose of study treatment
• The subject has active brain metastases or epidural disease (Note: Subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy i