Metastatic Advanced Pancreas Sorafenib (MAPS)

Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

Status and phase

Unknown

Phase 2

Conditions

Locally Advanced Pancreatic Cancer

Treatments

Drug: Gemcitabina, Cisplatino

Drug: Sorafenib 400 mg po bid, continuously

Study type

Interventional

Funder types

Other

Identifiers

NCT00758381

2007-001781-32

Details and patient eligibility

About

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.

Full 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.

Enrollment

114 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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).