Metastatic Advanced Pancreas Sorafenib

Study Overview
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Brief Summary
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This is multicentre, open-label, randomized, phase II trial in patients with locally advanced or metastatic pancreatic cancer. Subjects will be randomized in a 1:1 ratio to receive gemcitabine/cisplatin in combination with Sorafenib (arm A) or gemcitabine/cisplatin alone (arm B), as first-line chemotherapy.

Detailed Description
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Up to date no standard treatment is available for pancreatic cancer. Although gemcitabine is commonly used in patients with pancreatic cancer with the purpose of symptom palliation, there is no clear evidence of efficacy in terms of survival increase or progression control. Furthermore, attempts at improving results by combining gemcitabine with other cytotoxic drugs failed to obtain any advantage. Recently, an EGFR inhibitor (erlotinib) showed a small survival advantage when combined with gemcitabine. results obtained with a combination of gemcitabine and oxaliplatin seem more promising. A meta-analysis of randomised trials comparing gemcitabine versus gemcitabine and platinum analogues showed a statistical significant survival advantage for the combination. Sorafenib is an inhibitor of the RAS/RAF signalling pathway. Furthermore, sorafenib is able to inhibit both VEGFR and PDGFR. Since RAS and RAF mutations are quite common in pancreatic cancer, Sorafenib could be useful in the management of these tumours. Furthermore, it may be combined with gemcitabine and cisplatin without any pharmacokinetic interaction or enhanced toxicity.

Official Title
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A Randomized Phase II Study of Gemcitabine/Cisplatin With or Without Sorafenib to Evaluate the Efficacy and Safety in Patients With Locally Advanced or Metastatic Pancreatic Cancer. MAPS Trial

Conditions
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Locally Advanced Pancreatic Cancer

Intervention / Treatment
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* Drug: Sorafenib 400 mg po bid, continuously
* Drug: Gemcitabina, Cisplatino


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent prior to beginning protocol specific procedures Male or female 18 to 75 years of age Diagnosis of histologically confirmed adenocarcinoma of the pancreas Locally advanced (non-resectable) or metastatic pancreatic cancer Presence of at least one uni-dimensional indicator lesion measurable by CT scan or MRI in not an irradiated area (RECIST criteria) Karnofsky performance status of ≥ 70 at study entry Neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, and hemoglobin ≥ 9 g/dL Bilirubin level either normal or < 1.5 x ULN ASAT and ALAT ≤ 2.5 X ULN (≤ 5 x ULN if liver metastasis are present) Serum creatinine < 1.5 x ULN Amylase and lipase ≤ 1.5 x the upper limit of normal PT or INR and PTT < 1.5 x upper limit of normal (subjects who receive anti-coagulation treatment with an agent such as warfarin or heparin will be allowed to participate provided that no evidence of underlying abnormality in these parameters exists). Effective contraception for both male and female patients if the risk of conception exists Exclusion Criteria: Brain metastases Previous chemotherapy for locally advanced or metastatic pancreatic cancer. Adjuvant therapy if documented recurrence is within 6 months after the end of adjuvant treatment) Radiotherapy within 4 weeks prior to study entry Major surgery within 4 weeks of first dose of study drug Concurrent chronic systemic immune therapy Any investigational agent(s) 4 weeks prior to entry Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 6 months Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months Acute or subacute intestinal occlusion or history of inflammatory bowel disease Known grade 3 or 4 allergic reaction to any of the components of the treatment Known drug abuse/ alcohol abuse Legal incapacity or limited legal capacity Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent Women who are pregnant or breastfeeding Acute or subacute intestinal occlusion Any concurrent malignancy other than non-melanoma skin cancer, or carcinoma in situ of the cervix. (Patients with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the trial).

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Sorafenib 400 mg po bid, continuously Gemcitabine 1000 mg/m2, Cisplatin 25 mg/m2 day 1, and 8 every 21 days. | Drug: Sorafenib 400 mg po bid, continuously<br>* NEXAVAR*112CPR RIV 200MG Titolare AIC: BAYER SpA Numero di AIC dell'IMP: 037154010<br>* Other names: SORAFENIB TOSILATO;|
| Active Comparator: B<br>Gemcitabine 1000 mg/m2, Cisplatin 25 mg/m2 day 1, and 8 every 21 days | Drug: Gemcitabina, Cisplatino<br>* Gemcitabina 1000 mg/mq, Cisplatino 25 mg/mq day 1 and 8 every 21 days<br>* Other names: 026543025;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | time from randomization date to date of local or regional relapse | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - overall Response Rate (RECIST Criteria) - duration of response - overall survival time |  | time from the day of randomization to the date of death from any cause | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, advanced or metastatic, sorafenib