Clinical Trial to Investigate the Efficacy of Treatment With Gemcitabine/Pazopanib in Patients With Biliary Tree Cancer

NCT ID: NCT01855724

Last Updated: 2018-11-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-28
• Study Completion Date: 2018-09-28

Brief Summary

The purpose of this study is to determine whether gemcitabine and pazopanib are effective in the treatment of inoperable, locally advanced or metastatic biliary tree cancer (cholangiocarcinoma or gallbladder carcinoma).

Detailed Description

This is an open label, uncontrolled, multicenter, phase II study to evaluate the efficacy and safety of Gemcitabine/Pazopanib combination as 1st line treatment in patients with unresectable, locally advanced or metastatic biliary tree adenocarcinoma. A total of 46 patients will be included in the study. The patients will receive open label Gemcitabine 1000 mg/m2 intravenously on days 1 and 8 and Pazopanib 800 mg per os on days 1 to 21 every 21 days. Treatment with gemcitabine/pazopanib combination will continue until disease progression, appearance of significant toxicity, completion of 8 cycles or informed consent withdrawal. Upon completion of 8 treatment cycles with the combination, and in the absence of disease progression, administration of pazopanib monotherapy as maintenance treatment will be continued until disease progression, appearance of significant toxicity or informed consent withdrawal.

Imaging assessments will be performed every 8 weeks

Conditions

Cholangiocarcinoma; Gallbladder Carcinoma; Biliary Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gemcitabine-Pazopanib

Gemcitabine 1000 mg/m2 administered intravenously on days 1 and 8 and Pazopanib 800 mg administered per os on days 1 to 21 every 21 days.

Treatment with gemcitabine/pazopanib combination will continue until disease progression, appearance of significant toxicity, completion of 8 cycles or informed consent withdrawal.

Upon completion of 8 treatment cycles with the combination, and in the absence of disease progression, administration of pazopanib monotherapy as maintenance treatment will be continued until disease progression, appearance of significant toxicity or informed consent withdrawal.

Group Type: EXPERIMENTAL

Gemcitabine-Pazopanib

Intervention Type: DRUG

Interventions

Gemcitabine-Pazopanib

Intervention Type: DRUG

Other Intervention Names

Gemzar; Votrient

Eligibility Criteria

Inclusion Criteria

• Subjects must provide written informed consent prior to performance of study-specific procedures or assessments,and must be willing to comply with treatment and follow up.
• Age ≥18 years
• Histologically confirmed diagnosis of inoperable,locally advanced or metastatic cholangiocarcinoma (adenocarcinoma of intrahepatic,proximal extrahepatic,distal extrahepatic,gallbladder adenocarcinoma and periampullary bile duct adenocarcinoma).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Measurable disease criteria per RECIST v1.1.
• No prior chemotherapy or treatment with targeted therapy
• Formalin-fixed paraffin-embedded tumour and whole blood/plasma samples at diagnosis/study enrollment for biomarker studies.
• Adequate organ system function as specified in the protocol
• Female patients are allowed to participate provided they consent to avoid pregnancy throughout the course of the trial and 1 month after the last administration of the drug, if they are surgically sterilized or menopausal.

Exclusion Criteria

• Prior malignancy.Subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma or indolent prostate cancer are eligible (even if they are receiving antihormonal therapy).
• Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases are asymptomatic and have no requirement for steroids or enzyme-inducing anticonvulsants in the past 6 months.
• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal, 28 days prior to study treatment initiation.
• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including malabsorption syndrome, major resection of the stomach
• Corrected QT interval (QTc) >480 milliseconds using Bazett's formula
• History of myocardial infarction, unstable angina, symptomatic peripheral vascular disease or Class II,III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) or cardiac angioplasty or stenting within the past 6 months
• Newly-diagnosed hypertension or history of poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 millimeters of mercury (mmHg)or diastolic blood pressure (DBP) of ≥90mmHg].
• History of cerebrovascular accident including transient ischemic attack(TIA),pulmonary embolism or untreated deep venous thrombosis(DVT) within the past 6 months.Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
• Major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture,or ulcer (procedures such as catheter placement not considered to be major).
• Evidence of active bleeding or bleeding diathesis.
• Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage
• Recent hemoptysis (≥ ½ teaspoon of red blood within 8 weeks of first dose of study drug).
• Any serious and/or unstable pre-existing medical,psychiatric, or other condition that could interfere with subject's safety,provision of informed consent,or compliance to study procedures.
• Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug(whichever is longer) prior to the first dose of study drug and for the duration of the study
• Radiation therapy,surgery or tumor embolization within 14 days prior to the first dose of pazopanib
• Administration of any non-oncologic investigational study drug within 30 days or 5 half lives whichever is longer prior to receiving the first dose of study treatment.
• Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity, except alopecia.
• Pregnancy or lactation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Hellenic Cooperative Oncology Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph Sgouros, MD

Role: STUDY_CHAIR

3rd Dept of Medical Oncology, Agii Anargiri Cancer Hospital

Locations

2nd Dept of Internal Medicine, Agios Savvas Cancer Hospital

Athens, , Greece

Dept of Medical Oncology, 251 General Air Force Hospital

Athens, , Greece

2nd Dept of Internal Medicine, General Hospital of Athens "Hippokratio"

Athens, , Greece

Oncology Dept, 2nd Surgyc Clinic, Aretaieio Hospital

Athens, , Greece

Oncology Section, Dept of Clinical Therapeutics, General Hospital of Athens "Alexandra"

Athens, , Greece

Division of Oncology, 2nd Dept of Internal Medicine, Propaedeutic, University Hospital "Attikon"

Athens, , Greece

2nd Dept of Medical Oncology, Agii Anargiri Cancer Hospital

Athens, , Greece

3rd Dept of Medical Oncology, Agii Anargiri Cancer Hospital

Athens, , Greece

3rd Dept of Medical Oncology, Hygeia Hospital

Athens, , Greece

1st Dept of Medical Oncology, Metropolitan Hospital

Athens, , Greece

2nd Dept of Medical Oncology, Metropolitan Hospital

Athens, , Greece

Dept of Medical Oncology, University Hospital of Heraklion

Heraklion, , Greece

Dept of Medical Oncology, Ioannina University Hospital

Ioannina, , Greece

Division of Oncology, Dept of Internal Medicine, University Hospital of Patras

Pátrai, , Greece

2nd Dept of Medical Oncology, EUROMEDICA General Clinic of Thessaloniki

Thessaloniki, , Greece

Dept of Medical Oncology, Papageorgiou General Hospital

Thessaloniki, , Greece

Dept of Medical Oncology, Thermi Clinic S.A

Thessaloniki, , Greece

Countries

Greece

Other Identifiers

2012-001705-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

HE 37/12

Identifier Type: -

Identifier Source: org_study_id