Metastatic Advanced Pancreas Sorafenib

Study Overview

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.

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.

Locally Advanced Pancreatic Cancer

DRUG: Sorafenib 400 mg po bid, continuously
DRUG: Gemcitabina, Cisplatino

2007-001781-32

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2008-09-22	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2008-10-09
First Submitted that Met QC Criteria 2008-09-23	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2008-10-10
First Posted (ESTIMATED) 2008-09-25	Results First Posted N/A	Last Verified 2008-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

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
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

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

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

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

Secondary Outcome Measures	Measure Description	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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Stefano Cascinu, MProfessor

Phone Number: +39 071 5964

Email: cascinu@yahoo.com

Study Contact Backup

Name: Silvia Rota, Data Manager

Phone Number: +39 0331 490052

Email: centrotrialgiscad@yahoo.it

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Mario Negri Institute for Pharmacological Research

Investigators

STUDY_CHAIR: Stefano Cascinu, M.Professor, GISCAD Foundation

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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