Cabozantinib (XL-184) Monotherapy for Advanced Cholangiocarcinoma

Completed · Phase 2

Conditions studied: Bile Duct Cancer, Intrahepatic Cholangiocarcinoma, Cholangiocarcinoma of the Extrahepatic Bile Duct

In brief

This research study is evaluating a drug called cabozantinib as a possible treatment cancer of the bile duct. Cabozantinib is a drug that targets specific pathways inside the cells of the body. By blocking the c-MET and VEGFR2 pathways from sending signals, cabozantinib may prevent cells from multiplying. This drug has been used in other research studies and information from those other research studies suggests that this drug may help to stop the growth of bile duct cancer. In this research study, the investigators are looking to see how well cabozantinib works in slowing the growth of bile duct cancer. The investigators are also assessing the safety and tolerability of cabozantinib in participants with this type of cancer.

Key facts

Study ID

NCT01954745

Run by

Massachusetts General Hospital

People needed

19

Starts

2013-09-01

Expected to finish

2016-06-01

Last updated by the study team

2017-02-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must have unresectable or metastatic histologically or cytologically confirmed intrahepatic cholangiocarcinoma or extrahepatic cholangiocarcinoma (i.e. hilar and distal cholangiocarcinoma).
• 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 failed at least 1 but no more than 2 lines of systemic regimens for advanced cholangiocarcinoma due to disease progression or toxicity.
• Age ≥ 18 years.
• Life expectancy of ≥ 3 months.
• ECOG performance status < 1 (see Appendix A).
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count > 1,500/mcL
• Platelets > 100,000/mcL
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 2.0 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
• Lipase < 2.0 x the upper limit of normal and no radiologic or clinical evidence of pancreatitis
• Serum phosphorus, calcium, magnesium and potassium ≥ LLN
• Urine protein: creatinine ratio ≤ 1
• 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.

You may not qualify if…

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
• Prior treatment with cabozantinib or other VEGF-R directed therapies
• Gallbladder carcinoma or periampullary tumors
• Chemotherapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin) or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• The subject has received radiation therapy:
• to the thoracic cavity, abdomen or pelvis within 3 months of the first dose of study treatment or has with ongoing complications or is without complete recovery and healing from prior 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 a primary brain tumor.
• 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 is permitted if completed at least 3 months before starting study treatment. (Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility.)
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders including
• Congestive heart failure (CHF): New York Heart Association (NYHA) Class III (moderate) or Class IV (severe) at the time of screening
• Concurrent uncontrolled hypertension defined as sustained BP > 140 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
• Any history of congenital long QT syndrome
• Any of the following within 6 months before the first dose of study treatment:
• unstable angina pectoris
• clinically-significant cardiac arrhythmias
• stroke (including TIA, or other ischemic event)
• myocardial infarction
• thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter (e.g. vena cava filter) are not eligible for this study)
• Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
• Any of the following within 28 days before the first dose of study treatment
• intra-abdominal tumor/metastases invading GI mucosa
• active peptic ulcer disease,

Where it is running

• Massachusetts General Hospital — Boston, Massachusetts, United States
• Brigham and Women's Hospital — Boston, Massachusetts, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

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