Clinical Trial Comparing Gemcitabine and Vandetanib Therapy with Gemcitabine Alone in Pancreatic Carcinoma (ViP)

A Prospective, Phase II, Double Blinded, Multicentre, Randomised Clinical Trial Comparing Combination Gemcitabine and Vandetanib Therapy with Gemcitabine Therapy Alone in Locally Advanced or Metastatic Pancreatic Carcinoma

ViP is a double blinded clinical trial which will compare gemcitabine and vandetanib chemotherapy with gemcitabine alone in patients with locally advanced or metastatic pancreatic carcinoma.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Placebo; Drug: Caprelsa (vandetanib)

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Belfast City Hospital
  • Bournemouth, United Kingdom, BH7 7DW
    • The Royal Bournemouth Hospital
  • Bristol, United Kingdom, BS2 8ED
    • Bristol Haematology and Oncology Centre
  • Guildford, United Kingdom, GU2 7XX
    • Royal Surrey County Hospital
  • Liverpool, United Kingdom, L69 3GA
    • Royal Liverpool University Hospital
  • Liverpool, United Kingdom, CH63 4JY
    • Clatterbridge Centre for Oncology
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew'S Hospital
  • London, United Kingdom, SE1 9RT
    • Guys & St Thomas Hospital
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital
  • Middlesbrough, United Kingdom, Ts4 3Bw
    • James Cook University Hospital
  • Newcastle, United Kingdom, NE7 7DN
    • Freeman Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital
  • Sheffield, United Kingdom, S10 2SJ
    • Weston Park Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Histologically or cytologically proven pancreatic ductal adenocarcinoma or undifferentiated carcinoma of the pancreas.
• Locally advanced or metastatic disease precluding curative surgical resection or definitive locally directed therapies such as chemo radiation. Patients who have relapsed following previously resected Pancreatic Cancer can be included.
• Contrast enhanced computerised tomography (CT) scan of the thorax, abdomen and pelvis within 28 days prior to commencing treatment.
• Unidimensionally measurable disease as shown by CT scan, in accordance with RECIST guidelines (version 1.1)
• ECOG performance status 0, 1 or 2 where the investigator feels that treatment with combination chemotherapy.
• Platelets ≥100 x 109/l; WBC ≥ 3 x 109/l; neutrophils ≥ 1.5 x 109/l at entry.
• Documented Life expectancy > 3 months.
• Informed written consent

Exclusion Criteria:

• Laboratory results:

  • Serum bilirubin ≥ 1.5x the upper limit of reference range (ULRR).
  • Haemoglobin < 10G/dl
  • Creatinine clearance < 30 mL/minute (calculated by Cockcroft-Gault formula)**. Patients with a creatinine clearance of ≥30mL/minute and <50mL/minute should begin vandetanib on a reduced dose of 200mg.
  • Potassium, ≤4.0 mmol/L despite supplementation; or > 5.5 mmol/L
  • Magnesium below the normal range despite supplementation, or > 1.23 mmol/L
  • Serum calcium is > 2.9 mmol/L. In cases where serum calcium is below the normal range this can be substituted with the value for calcium adjusted for albumin, if this is below the normal range despite supplementation patients should be excluded.
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) or alkaline phosphatase (ALP) >2.5 x ULRR or > 5x ULRR if judged by the investigator to be related to liver metastases.
• Medical or psychiatric conditions compromising informed consent.
• Intracerebral metastases or meningeal carcinomatosis.
• Major surgery within 4 weeks or incompletely healed surgical incision before starting study therapy.
• Evidence of severe or uncontrolled systemic disease or any concurrent condition
• Clinically significant cardiovascular eventclassification of heart disease ≥2 within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
• History of arrhythmia which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded.
• QTc prolongation with other medications that required discontinuation of that medication.
• Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age.
• Presence of left bundle branch block (LBBB).
• QTc with Bazett's correction that is un-measurable or ≥ 480 msec on screening ECG. Patients who are receiving a drug that has a risk of inducing Torsades-de-Pointes are excluded if QTc is ≥ 460 msec.
• Any concurrent medication with a known risk of inducing Torsades-de-Pointes, that in the investigator's opinion cannot be discontinued, are allowed.
• Concomitant medications that are potent inducers.
• Hypertension not controlled by medical therapy.
• Currently active diarrhoea.
• Malabsorption syndrome.
• Pregnancy or breast feeding.
• Previous chemotherapy for locally advanced and metastatic disease. Adjuvant chemotherapy for resected pancreatic cancer will be permitted provided that chemotherapy was completed > 12 months previously.
• Radiotherapy within the last 4 weeks prior to start of study treatment.
• Concurrent malignancies or invasive cancers diagnosed within past 5 years.
• Chemotherapy directed at tumour apart from that described in this protocol.
• All men or women of reproductive potential, unless using at least two contraceptive precautions, one of which must be a condom.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Gemcitabine and Placebo; Standard therapeutic arm. Placebo orally once a day continuously together with gemcitabine 1000mg/m2 weekly as a 30 minute infusion for 7 consecutive weeks. This will then be followed by a one week break and then gemcitabine 1000mg/m2 weekly as a 30 minute infusion for 3 weeks followed by a one week break in subsequent cycles.	Drug: Placebo; Orally once a day, continuously throughout the study
Experimental: Gemcitabine and vandetanib; Experimental arm. Vandetanib orally once a day continuously together with gemcitabine 1000mg/m2 weekly as a 30 minute infusion for 7 consecutive weeks. This will then be followed by a one week break and then gemcitabine 1000mg/m2 weekly as a 30 minute infusion for 3 weeks followed by a one week break in subsequent cycles.	Drug: Caprelsa (vandetanib); Orally once a daily, continuously throughout the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	To assess whether survival times for patients receiving gemcitabine plus vandetanib are longer than for those patients receiving gemcitabine alone as first line treatment for advanced pancreatic cancer	Analysis will be carried out when all patients have a minimum of 1-year follow-up after randomisation

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival time	Analysis will be carried out when all patients have a minimum of 1-year follow-up after randomisation
Objective response rate	Analysis will be carried out when all patients have a minimum of 1-year follow-up after randomisation
Disease control rate	Analysis will be carried out when all patients have a minimum of 1-year follow-up after randomisation
Number and types of adverse events	Analysis will be carried out when all patients have a minimum of 1-year follow-up after randomisation
Patient pain assessment	Analysis will be carried out when all patients have a minimum of 1-year follow-up after randomisation

Collaborators and Investigators

• Sponsor: University of Liverpool
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Dr Gary Middleton, Royal Surrey County Hospital NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2011
• Primary Completion (Actual): September 5, 2018
• Study Completion (Actual): September 5, 2018

Study Registration Dates

• First Submitted: February 22, 2012
• First Submitted That Met QC Criteria: May 16, 2012
• First Posted (Estimated): May 18, 2012

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: 2010-021951-26; 74555382 (Other Identifier: ISRCTN)