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

• ClinicalTrials.gov Identifier: NCT01601808
• Recruitment Status: Unknown
• First Posted: May 18, 2012
• Last Update Posted: May 18, 2012
• Sponsor: University of Liverpool
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Dr Gary MIddleton, University of Liverpool

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pancreatic Cancer	Drug: Placebo; Drug: Caprelsa (vandetanib)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: October 2011
• Estimated Primary Completion Date: October 2012
• Estimated Study Completion Date: October 2013

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Overall survival [ Time Frame: Analysis will be carried out when all patients have a minimum of 1-year follow-up after randomisation ]
   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

Secondary Outcome Measures :

1. Progression-free survival time [ Time Frame: Analysis will be carried out when all patients have a minimum of 1-year follow-up after randomisation ]
2. Objective response rate [ Time Frame: Analysis will be carried out when all patients have a minimum of 1-year follow-up after randomisation ]
3. Disease control rate [ Time Frame: Analysis will be carried out when all patients have a minimum of 1-year follow-up after randomisation ]
4. Number and types of adverse events [ Time Frame: Analysis will be carried out when all patients have a minimum of 1-year follow-up after randomisation ]
5. Patient pain assessment [ Time Frame: Analysis will be carried out when all patients have a minimum of 1-year follow-up after randomisation ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Zaira Yunus; 0151 7948935; zyunus@liv.ac.uk

Locations

United Kingdom

Belfast City Hospital; Not yet recruiting

Belfast, United Kingdom, BT9 7AB

Principal Investigator: Dr Martin Eatock

The Royal Bournemouth Hospital; Recruiting

Bournemouth, United Kingdom, BH7 7DW

Principal Investigator: Dr Tamas Hickish

Bristol Haematology and Oncology Centre; Not yet recruiting

Bristol, United Kingdom, BS2 8ED

Principal Investigator: Dr Stephen Falk

Royal Surrey County Hospital; Recruiting

Guildford, United Kingdom, GU2 7XX

Principal Investigator: Dr Gary Middleton

Clatterbridge Centre for Oncology; Recruiting

Liverpool, United Kingdom, CH63 4JY

Principal Investigator: Professor Daniel Palmer

Royal Liverpool University Hospital; Recruiting

Liverpool, United Kingdom, L69 3GA

Principal Investigator: Professor Daniel Palmer

St Bartholomew's Hospital; Not yet recruiting

London, United Kingdom, EC1A 7BE

Principal Investigator: Dr David Propper

Guys & St Thomas Hospital; Recruiting

London, United Kingdom, SE1 9RT

Principal Investigator: Dr Paul Ross

Royal Marsden Hospital; Not yet recruiting

London, United Kingdom, SW3 6JJ

Principal Investigator: Professor David Cunningham

The Christie Hospital; Recruiting

Manchester, United Kingdom, M20 4BX

Principal Investigator: Dr Richard Hubner

James Cook University Hospital; Recruiting

Middlesbrough, United Kingdom, TS4 3BW

Principal Investigator: Dr Nick Wadd

Freeman Hospital; Not yet recruiting

Newcastle, United Kingdom, NE7 7DN

Principal Investigator: Dr Fareeda Coxon

Nottingham City Hospital; Recruiting

Nottingham, United Kingdom, NG5 1PB

Principal Investigator: Dr Srinivasan Madhusudan

Weston Park Hospital; Recruiting

Sheffield, United Kingdom, S10 2SJ

Principal Investigator: Dr Jonathan Wadsley

Sponsors and Collaborators

University of Liverpool

AstraZeneca

Investigators

• Principal Investigator: Dr Gary Middleton; Royal Surrey County Hospital NHS Foundation Trust

More Information

• Responsible Party: Dr Gary MIddleton, Consultant Medical Oncologist, University of Liverpool
• ClinicalTrials.gov Identifier: NCT01601808
• Other Study ID Numbers: 2010-021951-26; 74555382 ( Other Identifier: ISRCTN )
• First Posted: May 18, 2012
• Last Update Posted: May 18, 2012
• Last Verified: May 2012

Additional relevant MeSH terms:

Pancreatic Neoplasms; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases