Clinical trial NCT00536614: Gemcitabine/Cisplatin +/-Cetuximab in Patients With Locally Advanced or Metastatic EGFR-Positive Pancreatic Cancer
Official title: A Randomized Phase II Study of Gemcitabine/Cisplatin With or Without Cetuximab to Evaluate the Efficacy in Patients With Locally Advanced or Metastatic EGFR-EGFR-Positive Pancreatic Cancer. SpaCe Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: pancreatic cancer
metastatic
EGFR
locally advanced pancreatic cancer
Lead sponsor: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
Sponsor class: OTHER
Collaborators: name: Mario Negri Institute for Pharmacological Research
First posted: 2007-09-28
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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).

Primary outcomes:
measure: Overall survival
timeFrame: 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 outcomes:
measure: response to treatment, and toxicity
timeFrame: the time from randomization until the date of discontinuation of treatment or progression or death
Other outcomes:
Locations:
city: Treviglio
country: Italy
facility: A.O. Treviglio-Caravaggio, P.le Ospedale n1
state: Bergamo
city: Monza
country: Italy
facility: Ospedale S.Gerardo, Via Donizetti, 106
state: Milano
city: Ancona
country: Italy
facility: A.O. Ospedale Umberto I - Università - Località Torretta
city: Bergamo
country: Italy
facility: Ospedali Riuniti, Largo Barozzi, 1
city: Brescia
country: Italy
facility: Casa di Cura di Poliambulanza, Via Bissolati 57
city: Firenze
country: Italy
facility: A.O. Careggi-Università, Viale Pieraccini, 17
city: Livorno
country: Italy
facility: Azienda USL 6 - Viale Alfieri, 36
city: Mantova
country: Italy
facility: A.O. Carlo Poma - Via Albertoni, 1
city: Milano
country: Italy
facility: A.O. Cà Granda, Piazza Ospedale Maggiore, 3
city: Roma
country: Italy
facility: Università Campus Biomedico, Via Emilio Longoni, 83
Study officials:
affiliation: Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
name: Stefano Cascinu, MD
role: STUDY_CHAIR
References:
citation: 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.