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

NCT02053376 | Completed Phase 2 Results DMC

• 1 other identifier: 13-100
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Based on the facts of multiple pathways involvement in cholangiocarcinoma tumor genesis, including EGFR, Ras, Raf, VEGFR, and PDGFR, with evidence of overexpression of these proteins associated with tumor stage, prognosis and response to therapy. Multikinase inhibitor targeting multiple tumor pathways agent as regorafenib should be the ideal candidate for evaluating the anti-cancer activity for the disease as cholangiocarcinoma. More importantly, regorafenib likely holds promise in this disease setting with known effectiveness either as a single agent or in combination with cytotoxic chemotherapy agents in multiple solid tumors as above and the toxicity profile.

Conditions

Metastatic Biliary Tract Carcinoma

Keywords

gallbladder cancer, biliary cancer, bile duct cancer, hepatobiliary cancer, Biliary Tract Carcinoma; Cholangiocarcinoma

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS)

  Duration of time from start of treatment to time of progression or death, whichever occurs first. Per RECIST version 1.1, Progressive Disease (PD) is defined as: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

  Up to 4 years

• Progression-free Survival (PFS) - Two or More Doses

  Duration of time from start of treatment to time of progression or death, whichever occurs first. Per RECIST version 1.1, Progressive Disease (PD) is defined as: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

  up to 4 years

Secondary Outcomes (6)

• Proportion of Participants With Overall Response (OR)

  Up to 4 years

• Overall Survival (OS)

  Up to 4 years

• Overall Survival (OS) - Two or More Doses

  Up to 4 years

• Disease Control Rate (DCR)

  Up to 4 years

• Changes in Cancer Antigen 19-9 (CA19-9) Level

  At baseline prior to treatment and after all treatment received, up to 4 years

Study Arms (1)

regorafenib

EXPERIMENTAL

Patients with advanced and metastatic biliary tract adenocarcinoma (cholangiocarcinoma) who had been treated with and failed first-line chemotherapy will be treated with regorafenib (120 mg) (160 mg for second and subsequent treatment cycles) orally once daily 21 days (3 weeks) on and 7 days (1 week) off in the 28-day (4-week) cycle

Drug: Regorafenib

Interventions

Regorafenib DRUG

regorafenib (120 mg) (160 mg for second and subsequent treatment cycles)orally once daily 21 days (3 weeks) on and 7 days (1 week) off in the 28-day (4-week) cycle.

Also known as: STIVARGA

regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of biliary tract adenocarcinoma/cholangiocarcinoma (including primary intra- and extrahepatic diseases); 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 (including systemic and local-regional therapy).
• Age ≥ 18 years.
• Life expectancy of at least ≥ 12 weeks (3 months).
• Performance status ECOG ≤ 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) (biliary stenting or percutaneous biliary drainage are allowed for cancer related biliary obstruction)
• 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
• International normalized ratio (INR)/partial thromboplastin time (PTT) ≤ 1.5 x ULN. (Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care).
• Platelet count ≥ 75,000 /mm3
• Hemoglobin (Hb) ≥ 9 g/dL,
• Absolute neutrophil count (ANC) ≥ 1500/mm3.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nathan Bahary, MD: lead
• Bayer: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Gallbladder Neoplasms; Biliary Tract Neoplasms; Bile Duct Neoplasms; Cholangiocarcinoma

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Gallbladder Diseases; Bile Duct Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Barbara Stadterman, Regulatory Supervisor
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

412-647-5554

Study Officials

• Nathan Bahary, MD, PhD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 29, 2014
• First Posted: February 3, 2014
• Study Start: January 1, 2014
• Primary Completion: January 7, 2018
• Study Completion: May 14, 2018
• Last Updated: January 30, 2019
• Results First Posted: January 30, 2019

Record last verified: 2019-01

Locations

US (1)