Capecitabine/Erlotinib Followed of Gemcitabine Versus Gemcitabine/Erlotinib Followed of Capecitabine

Study Overview
=================
Brief Summary
-----------------
This crossover trial is performed in advanced and metastatic pancreatic cancer not previously exposed to chemotherapy. The study compares a standard arm with gemcitabine plus erlotinib to an experimental arm with capecitabine plus erlotinib. It is the first trial of its kind to incorporate second-line treatment into the study design. Patient who fail on first-line therapy are switched to the comparator chemotherapy without erlotinib. The trial therefore not only compares two different regimens of first-line treatment, it also compares two sequential treatment strategies.

Official Title
-----------------
Randomized Phase III Trial With Capecitabine/Erlotinib Followed of Gemcitabine Versus Gemcitabine/Erlotinib Followed of Capecitabine in Patients With Advanced Pancreatic Cancer

Conditions
-----------------
Pancreatic Cancer

Intervention / Treatment
-----------------
* Drug: Gemcitabine
* Drug: Capecitabine
* Drug: Erlotinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 18 and 75 years Histologically proven pancreatic cancer stage III or IV (T1-3 N1M0 or T1 3N0 1M1) No option for resection with curative intent At least one measurable or not measurable lesion (according to RECIST) No previous chemotherapy or other systemic tumor therapy No previous radiation Performance-Status 0-2 according to WHO/ECOG Life expectancy of at least 3 months Adequate kidney-, liver- and bone marrow function, defined as Absolute neutrophil count * 1,5 x 109/l Hemoglobin * 8 g/dl Thrombocytes * 100 x 109/l Bilirubin * 2 x upper norm (with liver mets < 5-fold) Serum Creatinine * 1,25 x upper norm Creatinine clearance > 30 ml/min (Cockroft/Gault) Transaminases * 2,5 x upper norm (with liver mets < 5-fold) Possibility of regular long-term follow-up Negative pregnancy test in women at childbearing age All patients must have signed an informed consent before study entry. Exclusion Criteria: Known secondary cancer other than curatively treated basalioma or carcinoma in situ of the cervix uteri Clinically unstable CNS-metastases Known hypersensitivity against study medication Severe impairment of renal function (creatinine clearance < 30 ml/min) Severe impairment of liver function (bilirubin > 2,0 x above upper norm, transaminases > 2,5 x upper norm, or with known liver metastasis >5 x upper norm) Clinically relevant disease of the cardiovascular system or other vital organs Known polyneuropathy Known DPD-deficiency (screening not required) Simultaneous treatment with the antiviral agent sorivudin or chemically related agents such as brivudin Pregnancy, lactation or lack of reliable contraception in women at childbearing age Mental disease, drug- or alcohol abuse Participation in another clinical trial within the last 4 weeks All other diseases which may prevent adequate participation in the trial Indication of lack of compliance with study regulations

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br> | Drug: Capecitabine<br>* Capecitabine 2 x 1000 mg/m²/ d oral, d 1 - 14 followed by 7 days Pause (Flat Dosing)<br>Drug: Erlotinib<br>* Erlotinib 150 mg/d oral, daily without break<br>|
| Active Comparator: Arm B<br> | Drug: Gemcitabine<br>* Gemcitabine 1000 mg/m², d 1, 8 , 15, q d28<br>Drug: Erlotinib<br>* Erlotinib 150 mg/d oral, daily without break<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TTF2 | Time to treatment failure, after 2nd line (crossover) therapy | approximate 6 months after first line treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TTF1 | Time to treatment failure | approximate 6 months after randomization | 
| Remission Rate |  | approximate 6 months after randomization | 
| Overall Survival |  | 42 months after randomization | 
| Clinical Benefit Response |  | approximate 6 months after randomization | 
| Tumor marker CA19-9 characteristics |  | approximate 6 months after randomization | 
| Quality of Life |  | approximate 6 months after randomization | 
| Toxicity |  | approximate 6 months after randomization | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
capecitabine, gemcitabine, Erlotinib, pancreatic cancer, advanced