Gemcitabine and Oxaliplatin (Gem-Ox) Plus Glivec in Gemcitabine-refractory Pancreatic Cancer (RPGOG1)

September 21, 2012 updated by: Royal Marsden NHS Foundation Trust

A Phase I Study of Gemcitabine Plus Oxaliplatin in Combination With Imatinib Mesylate (Glivec) in Patients With Gemcitabine-refractory Advanced Adenocarcinoma of the Pancreas

The main research objective is to work out the optimal doses of the novel combination of gemcitabine, oxaliplatin and imatinib mesylate (glivec) in patients with advanced pancreatic cancer that has progressed during or after treatment with first-line gemcitabine.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Using the phase I study design, the dose of gemcitabine will be escalated in several steps to identify the highest tolerable dose that can be given safely. Based on pre-defined dose-limiting toxicity, the maximum tolerated dose of the combination will be identified and a safer dose for further evaluation of this regimen in pancreatic cancer selected. The primary objectives are therefore based around safety of the drug combination.

Study Type

Interventional

Enrollment (Anticipated)

36

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Surrey
      • Sutton, Surrey, United Kingdom, SM2 5PT
        • Royal Marsden NHS Foundation Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • age > 18 years
  • gemcitabine-refractory, histologically confirmed pancreatic cancer (progression during or within 6 months of first-line treatment)
  • locally advanced or metastatic disease with measurable or non-measurable disease
  • life expectancy of greater than 10 weeks
  • prior treatment with investigational therapies including EGFR and VEGF antagonists is allowed when administered>4 weeks prior to start of therapy

Exclusion Criteria:

  • any serious uncontrolled medical condition
  • prior radiation treatment is not allowed
  • no prior chemotherapy within the previous 4 weeks
  • known peripheral neuropathy > CTCAE v 3.0 grade 1; absence of the deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible
  • known brain metastases
  • lack of physical integrity of the upper GI tract, malabsorption syndrome, or inability to take oral medication
  • fertile women (<2 years after last menstruation) and men of childbearing potential not willing to use effective contraception
  • pregnancy or breast feeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Treatment
Gemcitabine plus Oxaliplatin in combination with imatinib mesylate
Drug: Gemcitabine

The starting dose of gemcitabine will be 400 mg/m2 on day 1 of a two-week cycle.

Gemcitabine is given on day 1 every two weeks according to the dose escalation schedule below:

Dose level -1 200mg/m2 Dose level 1 400mg/m2 Dose level 2 600mg/m2 Dose level 3 800mg/m2 Dose level 4 1000mg/m2 Dose level 5 1000mg/m2 It is administered as an intravenous infusion, the lyophilized powder being diluted in normal saline, at a fixed dose of 10 mg/m2/minute.

Drug: Oxaliplatin
Oxaliplatin is given by intravenous infusion on day 2 every 2 weeks according to the dose escalation schedule below: Dose level -1 - 4 85mg/m2 Dose level 5 100mg/m2 Oxaliplatin should be diluted in 250 to 500 ml of 5% glucose solution to give a concentration not less than 0.2 mg/ml. It must be infused via a central venous line or peripheral vein over 2 hours. In the event of extravasation, administration must be discontinued immediately and the extravasation managed according to local procedures.
Drug: Imatinib

Imatinib is given for 7 days every cycle starting 2 days before the gemcitabine is given, including administration on days 1 and 2 when gemcitabine and oxaliplatin are given, and for 3 days afterwards (i.e. days -2 to +5). It is thus given on a 7 days on and 7 days off intermittent dosing schedule. The dose will be fixed at 400 mg daily in tablet form and taken once daily with food.

Imatinib should commence either in the morning or lunchtime of day -2 and be taken at the same time daily for seven consecutive days in total.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary outcome measure for the study is to establish the Maximum Tolerated Dose of the drug regimen based on the endpoint of dose-limiting toxicity
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Overall survival
Progression free survival
Response rate for those with measurable disease
Characterise safety profile of Gemcitabine Plus Oxaliplatin in Combination with imatinib mesylate (Glivec) in Patients with Gemcitabine-Refractory Advanced Adenocarcinoma of the Pancreas

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Royal Marsden NHS Foundation Trust

Investigators

  • Principal Investigator: David Cunningham, Royal Marsden NHS Foundation Trust

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Primary Completion (Actual)

December 1, 2010

Study Completion (Actual)

December 1, 2010

Study Registration Dates

First Submitted

January 11, 2010

First Submitted That Met QC Criteria

January 12, 2010

First Posted (Estimate)

January 13, 2010

Study Record Updates

Last Update Posted (Estimate)

September 25, 2012

Last Update Submitted That Met QC Criteria

September 21, 2012

Last Verified

September 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCR2731
  • EudraCT No: 2005-004022-99

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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