Clinical trial NCT00997009: Study of Adding Cetuximab to Chemotherapy for the Treatment of Advanced and/or Recurrent Cervical Cancer
Official title: Randomized Phase II Study of Carboplatin and Paclitaxel +/- Cetuximab, in Advanced and/or Recurrent Cervical Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Cervical Cancer
Keywords: EGFR
chemotherapy
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2009-10-16
Enrollment: 108
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to assess the activity of a combination of cetuximab (weekly) with carboplatin + paclitaxel (every three weeks) comparing it to chemotherapy alone in terms of event-free survival (EFS).

Detailed description: The poor long-term results in the standard treatment of chemotherapy for cervical cancer make research into new, more beneficial treatment strategies necessary. Cetuximab is a new type of drug that blocks the epidermal growth factor receptor (anti-EFGR), and has shown significant activity in other cancers (colon, head and neck) where expression of EGFR is high. Cervical cancer cells express EGFR in a very high proportion of cases, especially in recurrent or resistant disease. This study evaluates the activity of the addition of cetuximab to full doses of carboplatin and paclitaxel.

Eligibility criteria: Inclusion Criteria:

* Advanced and/or metastatic cervical cancer patients untreated or having failed only one previous chemotherapy (with at least 6 months of progression free interval, with or without concomitant or sequential radiotherapy).
* At baseline, presence of at least one measurable target lesion (a lesion that can be accurately measured in at least one dimension i.e. longest diameter at least 20 mm with conventional CT scan or at least 10 mm with spiral CT scan according to RECIST Criteria).
* Not amenable to surgery and/or radiotherapy.
* PS 0-1 according to ECOG.
* Age \>18.
* Life expectancy of at least 3 months.
* Adequate organ functions

  * Hematopoietic: Leukocytes \> 3,000/mm3; Absolute neutrophil count \> or = 1,500/mm3; Platelets count \> or = 100,000/mm3; Hemoglobin \> or = 9 g/dL
  * Hepatic: AST and ALT \< or = 3 times upper limit of normal (ULN)\*; Alkaline phosphatase \< or = 3 times ULN\*; Bilirubin \< or = 1.5 times ULN

    \*: \< or = 5 times ULN if liver metastases are present
  * Renal: Creatinine clearance \> or = 45 mL/min
* No other invasive malignancy within the past 5 years except non-melanoma skin cancer.
* All radiology studies must be performed within 28 days prior to randomization.
* Absence of any psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule.
* Written informed consent.

Exclusion Criteria:

* Pregnant (potentially fertile patients must use contraceptive measures to avoid pregnancy during and for at least 3 months after study participation and must have a negative serum pregnancy test at baseline).
* Patients should not be breast-feeding during treatment and for 2 months following the end of treatment.
* More than one previous chemotherapy line.
* Active infection requiring antibiotics.
* Symptomatic peripheral neuropathy \>grade 2 according to the CTCAE.
* Congestive heart failure or angina pectoris even if it is medically controlled. Previous history of myocardial infarction within 1 year from study entry, uncontrolled high risk hypertension or arrhythmia.
* Known hypersensitivity to the study drugs or to drugs with similar chemical structures.
* Concurrent treatment with other experimental drugs.
* Participation in another clinical trial with any investigational drug within 30 days prior to study screening.

Primary outcomes:
measure: event free survival
timeFrame: after 3 and 6 cycles of treatment (each cycle is 21 days), and every 3 months thereafter up to 18 months
Secondary outcomes:
measure: adverse events
timeFrame: after each treatment cycle (each cycle is 21 days) up to 30days
measure: overall survival
timeFrame: 18 months
measure: skin toxicity and correlation with cetuximab activity
timeFrame: after 3 and 6 cycles of therapy (each cycle is 21 days), and every 3 months thereafter up to 18 months
measure: EGFR/KRAS expression and correlation with cetuximab activity
timeFrame: at 18 months
Other outcomes:
Locations:
city: Brindisi
country: Italy
facility: Ospedale Senatore Antonio Perrino
city: Cagliari
country: Italy
facility: Ospedale Oncologico A. Businco
city: Campobasso
country: Italy
facility: Universita Cattolica del Sacro Cuore
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio e la Cura dei Tumori
city: Milano
country: Italy
facility: Istituto Nazionale Tumori
city: Modena
country: Italy
facility: A.O. Unversitaria Policlinico
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori , Oncologia Medica - Dipartimento Uro-Ginecologico
city: Napoli
country: Italy
facility: A.O. Universitaria Federico II
city: Napoli
country: Italy
facility: Seconda Università di Napoli
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Perugia
country: Italy
facility: Ospedale Silvestrini
city: Roma
country: Italy
facility: Istituto Regina Elena
city: Roma
country: Italy
facility: Universita Cattolica del Sacro Cuore
city: Trento
country: Italy
facility: Ospedale S. Chiara
city: Udine
country: Italy
facility: A.O. di Udine S. Maria della Misericordia
Study officials:
affiliation: National Cancer Institute, Naples
name: Sandro Pignata, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute, Naples
name: Francesco Perrone, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute, Naples
name: Alessandro Morabito, M.D.,
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Campania Luigi Vanvitelli
name: Ciro Gallo, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: