Metastatic Advanced Pancreas Sorafenib

Locally Advanced Pancreatic Cancer Clinical Trial

— MAPS  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00758381
• Other study ID #: 2007-001781-32
• Status: Recruiting
• Phase: Phase 2
• First received: September 22, 2008
• Last updated: October 9, 2008
• Start date: August 2007
• Est. completion date: August 2009

Study information

• Verified date: October 2008
• Source: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
• Contact: Stefano Cascinu, MProfessor
• Phone: +39 071 5964
• Email: cascinu[@]yahoo.com
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 114
• Est. completion date: August 2009
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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).

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Locally Advanced Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• Sorafenib 400 mg po bid, continuously
NEXAVAR*112CPR RIV 200MG Titolare AIC: BAYER SpA Numero di AIC dell'IMP: 037154010
• Gemcitabina, Cisplatino
Gemcitabina 1000 mg/mq, Cisplatino 25 mg/mq day 1 and 8 every 21 days

Locations

Country	Name	City	State
Italy	A.O. Universitaria Ospedali Riuniti Umberto I	Ancona
Italy	Ospedali Riuniti, Largo Barozzi, 1	Bergamo
Italy	A.O.Policlinico S.Orsola Malpighi	Bologna
Italy	Ospedale S.Orsola Fatebenefratelli	Brescia	BS
Italy	A.O. Careggi-Università, Viale Pieraccini, 17	Firenze
Italy	A.O. Ospedale S.Martino	Genova	GE
Italy	Ospedale Galliera	Genova
Italy	A.O. Carlo Poma - Via Albertoni, 1	Mantova
Italy	A.O. Cà Granda, Piazza Ospedale Maggiore, 3	Milano
Italy	A.O. san Paolo	Milano	MI
Italy	Casa di Cura Igea	Milano	MI
Italy	Ospedale S.Carlo Borromeo	Milano	MI
Italy	Policlinico di modena	Modena
Italy	A.O. S.Gerardo	Monza	MI
Italy	A.O. S.Giovanni Calabita Fatebenefratelli	Roma
Italy	Università Campus Biomedico, Via Emilio Longoni, 83	Roma
Italy	A.O. Treviglio-Caravaggio, P.le Ospedale n1	Treviglio	Bergamo

Sponsors (2)

Lead Sponsor	Collaborator
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente	Mario Negri Institute for Pharmacological Research

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival		time from randomization date to date of local or regional relapse	No
Secondary	- 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	Yes