Gemcitabine/Cisplatin +/-Cetuximab In Patients With Locally Advanced Or Metastatic EGFR-Positive Pancreatic Cancer

Study Overview

Gemcitabine/Cisplatin +/-Cetuximab in Patients With Locally Advanced or Metastatic EGFR-Positive Pancreatic Cancer

This is multicenter, open-label, randomized, phase II trial in patients with locally advanced or metastatic pancreatic cancer. Primary objective: objective response rate. Secondary objectives: safety, time to disease progression, median duration of response, time to treatment failure, overall survival time, correlation between bio-pathological characterization (EGFR, akt, MAPks) objective response and survival

During the last years, the esocrine pancreatic carcinoma presented a slow but constant increase of incidence. Chemotherapy determined disappointing results. Gemcitabine determined a slight advantage in survival and clinical benefit in comparison with gemcitabine with cisplatin or oxaliplatin Elevated expression of EGFR or its ligand correlates with worse prognosis in a variety of human cancers including pancreatic cancer. Therefore, blockade of EGFR activity would provide a novel strategy for the treatment of cancer. Cetuximab (C225) is a human/murine chimeric monoclonal antibody directed to the EGFR binding site. In a preclinical setting, Cetuximab has demonstrated anticancer activity both in cell culture experiments and in "in vivo" tumor xenograft animal model Since the combination of gemcitabine and cisplatin seems to be the more effective treatment for advanced pancreatic cancer and Cetuximab may improve activity of this combination we designed this phase II randomised trial to assess the role of Cetuximab in combination with gemcitabine and cisplatin in pancreatic cancer.

Pancreatic Cancer

GENETIC: cetuximab

2004-004309-69

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 2007-09-27	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2007-09-27
First Submitted that Met QC Criteria 2007-09-27	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2007-09-28
First Posted (ESTIMATED) 2007-09-28	Results First Posted N/A	Last Verified 2007-09

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
NO_INTERVENTION: A arm A) gemcitabine/cisplatin in combination with Cetuximab arm B) gemcitabine/cisplatin alone	GENETIC: cetuximab Cetuximab is an EGFR antibody inhibitor; it has been shown to increase the activity of gemcitabine (GEM) in advanced pancreatic cancer.

Participant Group/Arm

Intervention/Treatment

NO_INTERVENTION: A

arm A) gemcitabine/cisplatin in combination with Cetuximab arm B) gemcitabine/cisplatin alone

GENETIC: cetuximab

Cetuximab is an EGFR antibody inhibitor; it has been shown to increase the activity of gemcitabine (GEM) in advanced pancreatic cancer.

Primary Outcome Measures	Measure Description	Time Frame
Overall survival		A subject's survival time will be defined as the time from randomization to the date of his or her death. If the subject has not died, survival will be censored on last date the subject was known to be alive.

Secondary Outcome Measures	Measure Description	Time Frame
response to treatment, and toxicity		the time from randomization until the date of discontinuation of treatment or progression or death

Contacts and Locations

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

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:

Age ≥ 18 years
Histologically confirmed diagnosis of 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)
Immunohistochemical evidence or positive EGFR expression prior to study entry in primary tumor and/or at least one metastasis
Life expectancy of ≥ 3 months
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
Effective contraception for both, male and female patients if the risk of conception exists
Signed written informed consents prior to beginning protocol specific procedures

Brain metastasis
Previous chemotherapy for locally advanced or metastatic pancreatic cancer
Adjuvant therapy is allowed if recurrence is documented > 6 months after the end of adjuvant treatment
Radiotherapy within 4 weeks prior to study entry
Concurrent chronic systemic immune therapy
Any investigational agent(s) 4 weeks prior to entry
Previous exposure to EGF, monoclonal antibodies, signal transduction inhibitors or EGFR targeting therapy
Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months
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
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, MD, Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente

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

Cascinu S, Berardi R, Labianca R, Siena S, Falcone A, Aitini E, Barni S, Di Costanzo F, Dapretto E, Tonini G, Pierantoni C, Artale S, Rota S, Floriani I, Scartozzi M, Zaniboni A; Italian Group for the Study of Digestive Tract Cancer (GISCAD). Cetuximab plus gemcitabine and cisplatin compared with gemcitabine and cisplatin alone in patients with advanced pancreatic cancer: a randomised, multicentre, phase II trial. Lancet Oncol. 2008 Jan;9(1):39-44. doi: 10.1016/S1470-2045(07)70383-2.

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