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

Advanced Pancreatic Cancer Clinical Trial

— RPGOG1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01048320
• Other study ID #: CCR2731
• Secondary ID: EudraCT No: 2005
• Status: Completed
• Phase: Phase 1
• First received: January 11, 2010
• Last updated: September 21, 2012
• Start date: July 2006
• Est. completion date: December 2010

Study information

• Verified date: September 2012
• Source: Royal Marsden NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United Kingdom	Royal Marsden NHS Foundation Trust	Sutton	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
Royal Marsden NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		1 year	Yes
Secondary	Progression free survival			Yes
Secondary	Overall survival			Yes
Secondary	Response rate for those with measurable disease			Yes
Secondary	Characterise safety profile of Gemcitabine Plus Oxaliplatin in Combination with imatinib mesylate (Glivec) in Patients with Gemcitabine-Refractory Advanced Adenocarcinoma of the Pancreas			Yes