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
Overview
- Phase
- Phase 2
- Intervention
- Sorafenib 400 mg po bid, continuously
- Conditions
- Locally Advanced Pancreatic Cancer
- Sponsor
- Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
- Enrollment
- 114
- Locations
- 17
- Primary Endpoint
- Progression Free Survival
- Last Updated
- 17 years ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
A
Sorafenib 400 mg po bid, continuously Gemcitabine 1000 mg/m2, Cisplatin 25 mg/m2 day 1, and 8 every 21 days.
Intervention: Sorafenib 400 mg po bid, continuously
B
Gemcitabine 1000 mg/m2, Cisplatin 25 mg/m2 day 1, and 8 every 21 days
Intervention: Gemcitabina, Cisplatino
Outcomes
Primary Outcomes
Progression Free Survival
Time Frame: time from randomization date to date of local or regional relapse
Secondary Outcomes
- - 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)