SPaCe-01: Gemcitabine/Cisplatin +/-Cetuximab in Patients With Locally Advanced or Metastatic EGFR-Positive Pancreatic Cancer

Sponsor

Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente (Other)

Overall Status

Completed

CT.gov ID

NCT00536614

Collaborator

Mario Negri Institute for Pharmacological Research (Other)

Enrollment

Locations

Arm

Duration (Months)

8.6

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer	Genetic: cetuximab	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

86 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

May 1, 2005

Actual Study Completion Date :

Sep 1, 2006

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

response to treatment, and toxicity [the time from randomization until the date of discontinuation of treatment or progression or death]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	A.O. Treviglio-Caravaggio, P.le Ospedale n1	Treviglio	Bergamo	Italy	24047
2	Ospedale S.Gerardo, Via Donizetti, 106	Monza	Milano	Italy	20052
3	A.O. Ospedale Umberto I - Università - Località Torretta	Ancona		Italy	60020
4	Ospedali Riuniti, Largo Barozzi, 1	Bergamo		Italy	24128
5	Casa di Cura di Poliambulanza, Via Bissolati 57	Brescia		Italy	25100
6	A.O. Careggi-Università, Viale Pieraccini, 17	Firenze		Italy	50139
7	Azienda USL 6 - Viale Alfieri, 36	Livorno		Italy	57121
8	A.O. Carlo Poma - Via Albertoni, 1	Mantova		Italy	46100
9	A.O. Cà Granda, Piazza Ospedale Maggiore, 3	Milano		Italy	20162
10	Università Campus Biomedico, Via Emilio Longoni, 83	Roma		Italy	00155