Clinical trial NCT00758381: Metastatic Advanced Pancreas Sorafenib
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Locally Advanced Pancreatic Cancer
Keywords: pancreatic cancer
advanced or metastatic
sorafenib
Lead sponsor: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
Sponsor class: OTHER
Collaborators: name: Mario Negri Institute for Pharmacological Research
First posted: 2008-09-25
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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
* 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).

Primary outcomes:
measure: Progression Free Survival
timeFrame: time from randomization date to date of local or regional relapse
Secondary outcomes:
measure: - overall Response Rate (RECIST Criteria) - duration of response - overall survival time
timeFrame: time from the day of randomization to the date of death from any cause
Other outcomes:
Locations:
city: Treviglio
country: Italy
facility: A.O. Treviglio-Caravaggio, P.le Ospedale n1
state: Bergamo
city: Brescia
country: Italy
facility: Ospedale S.Orsola Fatebenefratelli
state: BS
city: Genova
country: Italy
facility: A.O. Ospedale S.Martino
state: GE
city: Milano
country: Italy
facility: A.O. san Paolo
state: MI
city: Milano
country: Italy
facility: Casa di Cura Igea
state: MI
city: Milano
country: Italy
facility: Ospedale S.Carlo Borromeo
state: MI
city: Monza
country: Italy
facility: A.O. S.Gerardo
state: MI
city: Ancona
country: Italy
facility: A.O. Universitaria Ospedali Riuniti Umberto I
city: Bergamo
country: Italy
facility: Ospedali Riuniti, Largo Barozzi, 1
city: Bologna
country: Italy
facility: A.O.Policlinico S.Orsola Malpighi
city: Firenze
country: Italy
facility: A.O. Careggi-Università, Viale Pieraccini, 17
city: Genova
country: Italy
facility: Ospedale Galliera
city: Mantova
country: Italy
facility: A.O. Carlo Poma - Via Albertoni, 1
city: Milano
country: Italy
facility: A.O. Cà Granda, Piazza Ospedale Maggiore, 3
city: Modena
country: Italy
facility: Policlinico di modena
city: Roma
country: Italy
facility: Università Campus Biomedico, Via Emilio Longoni, 83
city: Roma
country: Italy
facility: A.O. S.Giovanni Calabita Fatebenefratelli
Study officials:
affiliation: GISCAD Foundation
name: Stefano Cascinu, M.Professor
role: STUDY_CHAIR
References: