Metastatic Advanced Pancreas Sorafenib (MAPS)

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

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.

Study Overview

• Status: Unknown
• Conditions: Locally Advanced Pancreatic Cancer
• Intervention / Treatment: Drug: Sorafenib 400 mg po bid, continuously; Drug: Gemcitabina, Cisplatino

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.

• Study Type: Interventional
• Enrollment (Anticipated): 114
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Stefano Cascinu, MProfessor; Phone Number: 171 +39 071 5964; Email: cascinu@yahoo.com
• Study Contact Backup: Name: Silvia Rota, Data Manager; Phone Number: +39 0331 490052; Email: centrotrialgiscad@yahoo.it

Study Locations

• Italy
  • Ancona, Italy, 60020
    • Recruiting
    • A.O. Universitaria Ospedali Riuniti Umberto I
    • Principal Investigator: Stefano Cascinu, M.Pr
  • Bergamo, Italy, 24128
    • Recruiting
    • Ospedali Riuniti, Largo Barozzi, 1
  • Bologna, Italy, 40138
    • Active, not recruiting
    • A.O.Policlinico S.Orsola Malpighi
  • Firenze, Italy, 50139
    • Recruiting
    • A.O. Careggi-Università, Viale Pieraccini, 17
    • Sub-Investigator: Francesco Di Costanzo, MD
  • Genova, Italy, 16132
    • Active, not recruiting
    • Ospedale Galliera
  • Mantova, Italy, 46100
    • Recruiting
    • A.O. Carlo Poma - Via Albertoni, 1
    • Sub-Investigator: Enrico Aitini, MD
  • Milano, Italy, 20162
    • Recruiting
    • A.O. Cà Granda, Piazza Ospedale Maggiore, 3
    • Sub-Investigator: Salvatore Siena, MPr
  • Modena, Italy, 41100
    • Active, not recruiting
    • Policlinico di Modena
  • Roma, Italy, 00155
    • Active, not recruiting
    • Università Campus Biomedico, Via Emilio Longoni, 83
  • Roma, Italy, 00186
    • Active, not recruiting
    • A.O. S.Giovanni Calabita Fatebenefratelli
  • BS
    • Brescia, BS, Italy, 15100
      • Active, not recruiting
      • Ospedale S.Orsola Fatebenefratelli
  • Bergamo
    • Treviglio, Bergamo, Italy, 24047
      • Recruiting
      • A.O. Treviglio-Caravaggio, P.le Ospedale n1
      • Sub-Investigator: sandro Barni, MD
  • GE
    • Genova, GE, Italy, 16132
      • Recruiting
      • A.O. Ospedale S.Martino
      • Sub-Investigator: Alberto Sobrero, MD
  • MI
    • Milano, MI, Italy, 20100
      • Recruiting
      • A.O. san Paolo
      • Sub-Investigator: Paolo Foa, MD
    • Milano, MI, Italy, 20100
      • Not yet recruiting
      • Casa di Cura IGEA
      • Sub-Investigator: Gianfranco Pancera, MD
    • Milano, MI, Italy, 20123
      • Not yet recruiting
      • Ospedale S.Carlo Borromeo
      • Sub-Investigator: Donata Tabiadon, MD
    • Monza, MI, Italy, 20052
      • Recruiting
      • A.O. S.Gerardo
      • Sub-Investigator: Paolo Bidoli, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; 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; NEXAVAR*112CPR RIV 200MG Titolare AIC: BAYER SpA Numero di AIC dell'IMP: 037154010; Other Names: L01XE05 V; Sostanza attiva o descrizione del livello ATC selezionato; SORAFENIB TOSILATO
Active Comparator: B; Gemcitabine 1000 mg/m2, Cisplatin 25 mg/m2 day 1, and 8 every 21 days	Drug: Gemcitabina, Cisplatino; Gemcitabina 1000 mg/mq, Cisplatino 25 mg/mq day 1 and 8 every 21 days; Other Names: GEMZAR*INFUS 1FL 1G POLV; Titolare AIC:; ELI LILLY ITALIA SpA; Numero di AIC dell'IMP:; 029452012; CISPLATINO TEVA*EV 50MG 100ML; TEVA PHARMA ITALIA Srl; 026543025

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
• Collaborators: Mario Negri Institute for Pharmacological Research
• Investigators: Study Chair: Stefano Cascinu, M.Professor, GISCAD Foundation

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Anticipated): August 1, 2008
• Study Completion (Anticipated): August 1, 2009

Study Registration Dates

• First Submitted: September 22, 2008
• First Submitted That Met QC Criteria: September 23, 2008
• First Posted (Estimate): September 25, 2008

Study Record Updates

• Last Update Posted (Estimate): October 10, 2008
• Last Update Submitted That Met QC Criteria: October 9, 2008
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: pancreatic cancer; sorafenib; advanced or metastatic
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Cisplatin; Sorafenib
• Other Study ID Numbers: 2007-001781-32