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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01048320
Recruitment Status : Completed
First Posted : January 13, 2010
Last Update Posted : September 25, 2012
Information provided by:
Royal Marsden NHS Foundation Trust

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced Pancreatic Cancer Drug: Gemcitabine Drug: Oxaliplatin Drug: Imatinib Phase 1

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  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of Gemcitabine Plus Oxaliplatin in Combination With Imatinib Mesylate (Glivec) in Patients With Gemcitabine-refractory Advanced Adenocarcinoma of the Pancreas
Study Start Date : July 2006
Actual Primary Completion Date : December 2010
Actual Study Completion Date : December 2010

Resource links provided by the National Library of Medicine

Arm Intervention/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.

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Progression free survival
  2. Overall survival
  3. Response rate for those with measurable disease
  4. Characterise safety profile of Gemcitabine Plus Oxaliplatin in Combination with imatinib mesylate (Glivec) in Patients with Gemcitabine-Refractory Advanced Adenocarcinoma of the Pancreas

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01048320

United Kingdom
Royal Marsden NHS Foundation Trust
Sutton, Surrey, United Kingdom, SM2 5PT
Sponsors and Collaborators
Royal Marsden NHS Foundation Trust
Principal Investigator: David Cunningham Royal Marsden NHS Foundation Trust

Responsible Party: Professor David Cunningham, Royal Marsden NHS Foundation Trust Identifier: NCT01048320     History of Changes
Other Study ID Numbers: CCR2731
EudraCT No: 2005-004022-99
First Posted: January 13, 2010    Key Record Dates
Last Update Posted: September 25, 2012
Last Verified: September 2012

Keywords provided by Royal Marsden NHS Foundation Trust:
pancreatic cancer
dose finding

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Imatinib Mesylate
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors