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

Sponsor

Royal Marsden NHS Foundation Trust (Other)

Overall Status

Completed

CT.gov ID

NCT01048320

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Anticipated 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 :

Jul 1, 2006

Actual Primary Completion Date :

Dec 1, 2010

Actual Study Completion Date :

Dec 1, 2010

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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]

Secondary Outcome Measures

Progression free survival []
Overall 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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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