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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Hellenic Cooperative Oncology Group
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Hellenic Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT01855724
First received: May 14, 2013
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

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).


Condition Intervention Phase
Cholangiocarcinoma
Gallbladder Carcinoma
Biliary Carcinoma
Drug: Gemcitabine-Pazopanib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Single-arm Study of First Line Treatment With Gemcitabine and Pazopanib in Patients With Inoperable Locally Advanced or Metastatic Biliary Tree Cancer (Cholangiocarcinoma or Gallbladder Carcinoma)

Resource links provided by NLM:


Further study details as provided by Hellenic Cooperative Oncology Group:

Primary Outcome Measures:
  • Objective Response Rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: At an average of 6 months for each patient ] [ Designated as safety issue: No ]
    Imaging evaluation for the determination of response to treatment will be performed every 8 weeks


Secondary Outcome Measures:
  • Evaluation of Progression-Free Survival (PFS) [ Time Frame: PFS will be calculated from the date of treatment initiation to the date of disease progression or date of death, assessed up to 48 months ] [ Designated as safety issue: No ]
  • Evaluation of 6-month Progression-Free Survival rate (6-month PFS rate) [ Time Frame: Assessed up to 6 months ] [ Designated as safety issue: No ]
    The aim is to determine the rate of PFS in patients, at 6 months of treatment

  • Evaluation of Overall Survival (OS) [ Time Frame: OS will be calculated from the date of treatment initiation to the date of death from any cause, assessed up to 48 months. ] [ Designated as safety issue: No ]
  • Assessment of safety and tolerability [ Time Frame: Assessed up to 48 months ] [ Designated as safety issue: Yes ]
    Distribution of Adverse Events (AEs) according to severity grade. Evaluation of AEs will be performed every 21 days (per treatment cycle) throughout the course of treatment

  • Evaluation of Quality of Life (QoL) [ Time Frame: Assessed up to 9 months ] [ Designated as safety issue: No ]
    Quality of Life Questionnaires will be filled out before treatment initiation, every 8 weeks and at the end of treatment

  • Evaluation of potential prognostic and/or predictive biomarkers in tissue and blood samples [ Time Frame: Tumor blocks and blood samples will be collected at baseline ] [ Designated as safety issue: No ]

    The following biomarkers will be analyzed:

    In bioptic material:

    • Stem Cell Factor (KIT)
    • Vascular Endothelial Growth Factor Receptor-2 (VEGF-2)
    • Vascular Endothelial Growth Factor Receptor-3 (VEGF-3)

    In peripheral blood/plasma:

    • Interleukin 8
    • Interleukin 12
    • Hepatocyte growth factor

    There may be additions to the biomarkers to be analyzed, dependent on the clinical and bibliographical data



Estimated Enrollment: 46
Study Start Date: June 2013
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: Gemcitabine-Pazopanib
Other Names:
  • Gemzar
  • Votrient

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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 ClinicalTrials.gov identifier: NCT01855724

Contacts
Contact: Joseph Sgouros, MD 0030 210 3501273 josephsgouros@yahoo.co.uk

Locations
Greece
3rd Dept of Medical Oncology, Agii Anargiri Cancer Hospital Recruiting
Athens, Greece, 14564
Contact: Joseph Sgouros, MD       josephsgouros@yahoo.co.uk   
Principal Investigator: Joseph Sgouros, MD         
Oncology Section, Dept of Clinical Therapeutics, General Hospital of Athens "Alexandra" Recruiting
Athens, Greece, 11528
Contact: Christos Papadimitriou, Ass.Prof.       chr_papadim@yahoo.gr   
Principal Investigator: Christos Papadimitriou, Ass.Prof.         
Division of Oncology, 2nd Dept of Internal Medicine, Propaedeutic, University Hospital "Attikon" Recruiting
Athens, Greece, 12462
Contact: Diamanto Psyrri, Lecturer       psyrri237@yahoo.com   
Principal Investigator: Diamanto Psyrri, Lecturer         
2nd Dept of Internal Medicine, Agios Savvas Cancer Hospital Recruiting
Athens, Greece, 11522
Contact: George Koumakis, MD       gkoumak@otenet.gr   
Principal Investigator: George Koumakis, MD         
2nd Dept of Medical Oncology, Metropolitan Hospital Recruiting
Athens, Greece, 18547
Contact: Dimosthenis V. Skarlos, MD       hecogiat@otenet.gr   
Principal Investigator: Dimosthenis V. Skarlos, MD         
1st Dept of Medical Oncology, Metropolitan Hospital Recruiting
Athens, Greece, 18547
Contact: Dimitrios Bafaloukos, MD       dimmp@otenet.gr   
Principal Investigator: Dimitrios Bafaloukos, MD         
2nd Dept of Internal Medicine, General Hospital of Athens "Hippokratio" Recruiting
Athens, Greece, 11527
Contact: Dimitrios Pectasides, Professor       pectasid@otenet.gr   
Principal Investigator: Dimitrios Pectasides, Professor         
3rd Dept of Medical Oncology, Hygeia Hospital Recruiting
Athens, Greece, 15123
Contact: Evangelia Razis, MD       e.razis@hygeia.gr   
Principal Investigator: Evangelia Razis, MD         
Dept of Medical Oncology, Ioannina University Hospital Recruiting
Ioannina, Greece, 45500
Contact: George Pentheroudakis, Ass.Prof.       gpenther@otenet.gr   
Principal Investigator: George Pentheroudakis, Ass.Prof.         
Division of Oncology, Dept of Internal Medicine, University Hospital of Patras Recruiting
Patras, Greece, 26504
Contact: Thomas Makatsoris, Lecturer       maktom@yahoo.com   
Principal Investigator: Thomas Makatsoris, Lecturer         
Dept of Medical Oncology, Papageorgiou General Hospital Recruiting
Thessaloniki, Greece, 56429
Contact: George Fountzilas, Professor       fountzil@auth.gr   
Principal Investigator: George Fountzilas, Professor         
Sponsors and Collaborators
Hellenic Cooperative Oncology Group
GlaxoSmithKline
Investigators
Study Chair: Joseph Sgouros, MD 3rd Dept of Medical Oncology, Agii Anargiri Cancer Hospital
  More Information

No publications provided

Responsible Party: Hellenic Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT01855724     History of Changes
Other Study ID Numbers: HE 37/12, 2012-001705-24
Study First Received: May 14, 2013
Last Updated: June 12, 2014
Health Authority: Greece:National Organization for Medicines
Greece:National Ethics Committee
Greece:Ministry of Health and Social Solidarity

Additional relevant MeSH terms:
Carcinoma
Cholangiocarcinoma
Gallbladder Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Biliary Tract Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Biliary Tract Diseases
Digestive System Diseases
Gallbladder Diseases
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 18, 2014