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A Phase 2 Trial of Regorafenib as A Single Agent in Advanced and Metastatic Biliary Tract Carcinoma/Cholangiocarcinoma Patients Who Have Failed First-line Chemotherapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2016 by Weijing Sun, MD, FACP, University of Pittsburgh
Information provided by (Responsible Party):
Weijing Sun, MD, FACP, University of Pittsburgh Identifier:
First received: January 29, 2014
Last updated: October 24, 2016
Last verified: October 2016

As noted, multiple pathways, including epidermal growth factor receptor (EGFR), Ras, Raf, Vascular Endothelial Growth Factor Receptors (VEGFR), and platelet-derived growth factor (PDGFR) appear to be involved in cholangiocarcinoma tumor genesis. Overexpression of these proteins has been shown to be associated with tumor stage, prognosis, and response to therapy. However, therapies targeting a single pathway have shown no clear benefit. A number of Phase 2 trials have been completed, or are underway, studying agents targeted to EGFR or VEGF - both as monotherapy and in combination with chemotherapy. These have shown varying increases in response rate, but have not found marked increases in progression-free or overall survival. This suggests that inhibition of multiple pathways simultaneously may be needed. Regorafenib, is an oral multikinase inhibitor targeting multiple tumor pathways, which has showed effectiveness as a single agent in multiple solid tumors.

The primary objective of this clinical trial is to evaluate the progression-free survival (PFS) of patients receiving regorafenib after failing first-line chemotherapy. Patients with advanced and metastatic biliary tract adenocarcinoma (cholangiocarcinoma) who had been treated with and failed first-line chemotherapy will be treated with regorafenib (160 mg) orally once daily 21 days (3 weeks) on and 7 days (1 week) off in the 28-day (4-week) cycle.

Condition Intervention Phase
Metastatic Biliary Tract Carcinoma
Drug: Regorafenib
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Trial of Regorafenib as A Single Agent in Advanced and Metastatic Biliary Tract Carcinoma/Cholangiocarcinoma Patients Who Have Failed First-line Chemotherapy

Resource links provided by NLM:

Further study details as provided by Weijing Sun, MD, FACP, University of Pittsburgh:

Primary Outcome Measures:
  • Progression-free survival (PFS) of patients with advanced or metastatic biliary cancer receiving regorafenib [ Time Frame: up to 4 years ]

Secondary Outcome Measures:
  • • Overall response (OR) [ Time Frame: Up to 4 years ]
    Including complete and partial response, and disease Control rate (DCR)

  • Overall survival (OS) [ Time Frame: up to 4 years ]
  • Measurable changes in biomarkers [Cancer antigen 19-9 (CA19-9) and Carcinoembryonic antigen (CEA)] [ Time Frame: up to 4 years ]

Estimated Enrollment: 37
Study Start Date: January 2014
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: regorafenib
Patients with advanced and metastatic biliary tract adenocarcinoma (cholangiocarcinoma) who had been treated with and failed first-line chemotherapy will be treated with regorafenib (160 mg) orally once daily 21 days (3 weeks) on and 7 days (1 week) off in the 28-day (4-week) cycle
Drug: Regorafenib
regorafenib (120 mg) orally once daily 21 days (3 weeks) on and 7 days (1 week) off in the 28-day (4-week) cycle.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of biliary tract adenocarcinoma/cholangiocarcinoma; pathologic confirmation may be from the primary or a metastatic site
  • Must have locally advanced or distant metastatic disease that is not surgically curable
  • Failed first-line chemotherapy.
  • Age ≥ 18 years.
  • Life expectancy of at least 12 weeks (3 months).
  • Performance status < 1
  • Adequate liver, kidney, and bone marrow function as assessed by the following laboratory requirements:

    • Total bilirubin ≤ 3.0 x the upper limit of normal (ULN)
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5.0 x ULN
    • Alkaline phosphastase limit ≤ 2.5 x ULN (≤ 5.0 x ULN for subjects with intrahepatic involvement of their cancer)
    • Serum creatinine ≤ 1.5 x the ULN
    • Serum Amylase and Lipase ≤1.5 x the ULN.
    • International normalized ratio (INR)/partial thromboplastin time (PTT) ≤ 1.5 x ULN

Exclusion Criteria:

  • Previous assignment to treatment during this study. Subjects permanently withdrawn from study participation will not be allowed to re-enter study.
  • Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg on repeated measurement) despite optimal medical management.
  • Active or clinically significant cardiac disease including:

    • Congestive heart failure - New York Heart Association (NYHA) > Class II
    • Active coronary artery disease.
    • Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
    • Unstable angina (angina symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before randomization.
  • Evidence or history of bleeding diathesis or coagulopathy.
  • Any hemorrhage or bleeding event ≥ Grade 3 within 4 weeks prior to prior to registration.
  • Patients with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of the study registration.
  • Previous exposure to Vascular endothelial growth factor (VEGF) inhibitor(s),
  • Patients with any previously untreated or concurrent cancer that is distinct in primary site or histology from biliary tract cancer except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor. Patients surviving a cancer that was curatively treated and without evidence of disease for more than 3 years prior to registration are allowed. All cancer treatments must be completed at least 3 years prior to prior to registration).
  • Patients with phaeochromocytoma.
  • Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy.
  • Ongoing infection > Grade 2.
  • Symptomatic metastatic brain or meningeal tumors.
  • Presence of a non-healing wound, non-healing ulcer, or bone fracture.
  • Renal failure requiring hemo-or peritoneal dialysis.
  • Dehydration Grade ≥1
  • Patients with seizure disorder requiring medication.
  • Proteinuria >/= Grade 3 (> 3.5 g/24 hours, measured by urine protein: creatinine ratio on a random urine sample).
  • Active signs and symptoms of interstitial lung disease pleural effusion or ascites that causes respiratory compromise (≥ Grade 2 dyspnea).
  • History of organ allograft (including corneal transplant).
  • Known or suspected allergy or hypersensitivity to any of the study drug classes.
  • Any malabsorption condition.
  • Women who are pregnant or breast-feeding.
  • Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
  • Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.
  • Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than study treatment regorafenib. However, the palliative external beam radiation therapy (XRT) to non-targeted lesions is allowed.
  • Prior use of regorafenib.
  • Concurrent use of another investigational drug or device therapy (i.e., outside of study treatment) during, or within 28 days prior to registration
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration (biliary stenting or percutaneous biliary drainage are not included).
  • Use of any herbal remedy (e.g. St. John's Wort [Hypericum perforatum])
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02053376

Contact: Natalie Streeter, RN 412-235-1276

United States, Pennsylvania
Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Weijing Sun, MD    412-323-3283   
Sponsors and Collaborators
University of Pittsburgh
Principal Investigator: Weijing Sun, MD University of Pittsburgh CancerCenters
  More Information

Responsible Party: Weijing Sun, MD, FACP, Director of GI Cancers Section of Hematology-Oncology, University of Pittsburgh Identifier: NCT02053376     History of Changes
Other Study ID Numbers: 13-100
Study First Received: January 29, 2014
Last Updated: October 24, 2016

Keywords provided by Weijing Sun, MD, FACP, University of Pittsburgh:
gallbladder cancer, biliary cancer, bile duct cancer, hepatobiliary cancer, Biliary Tract Carcinoma

Additional relevant MeSH terms:
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma processed this record on May 25, 2017