Clinical trial NCT00330746: CALC-1 (Cetuximab in Advanced Lung Cancer): Study of 2 Methods of Combining Cetuximab and Gemcitabine in Patients With Advanced Non Small-cell Lung Cancer
Official title: Randomized Phase II Study of Cetuximab in Combination With Gemcitabine or Gemcitabine Followed by Cetuximab in Advanced Non Small-cell Lung Cancer Patients Who Are Not Candidates for Platinum Based Therapy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Non-Small Cell Lung Cancer
Keywords: elderly
chemotherapy
targeted therapy
combination therapy
sequential therapy
randomized phase II
one year survival
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2006-05-29
Enrollment: 100
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: The purpose of this study is to select the more promising method of combining cetuximab with gemcitabine for treating patients with advanced non small-cell lung cancer, who are not candidates for platinum based therapy.

Detailed description: The standard treatment for advanced non small cell lung cancer (NSCLC) is combination chemotherapy with cisplatin or carboplatin. Due to its toxicity, this therapy may not be suited for certain patients including the elderly, those whose general condition is poor. Combining chemotherapy with a biologic agent ("targeted therapy") is a new strategy being evaluated for the treatment of NSCLC, and cetuximab is one of the drugs that has shown promise for its activity and tolerability. This study aims to determine the more promising of 2 methods of combining gemcitabine with cetuximab (in combination vs. sequential administration), in two groups of patients who are not candidates for combination platinum based chemotherapy: patients under age 70 with performance status 2 (expected enrollment 42) , and patients over age 70 (expected enrollment 58).

Patients will be randomly assigned to one of two treatment arms:

* Arm A: Cetuximab + Gemcitabine:

  * Cetuximab given intravenously weekly AND
  * Gemcitabine given intravenously for a maximum of 6 cycles (on days 1 and 8 of each 3 week cycle)
* Arm B: Gemcitabine followed by Cetuximab:

  * Gemcitabine given intravenously for a maximum of 6 cycles (on days 1 and 8 of each 3 week cycle) THEN
  * Cetuximab given intravenously weekly

In Arm B, Cetuximab is administered as maintenance therapy when there has been an objective response to chemotherapy, or as second line therapy in patients who had disease progression during chemotherapy

Eligibility criteria: Inclusion Criteria:

* Signed written informed consent
* Age \> 18
* Histological diagnosis of non small-cell lung cancer (NSCLC)
* Stage III B or Stage IV disease
* Contraindications to platinum based therapy (age \> 70 or age \< 70 with ECOG performance status 2)
* At least one site of metastasis (target or non-target)
* Life expectancy of at least 3 months
* ECOG \<3
* Neutrophils \> 1500/mm3, platelets \> 100,000/mm3, hemoglobin \> 9g/dl
* Bilirubin \< 1.5 x the upper normal limit
* SGOT and SGPT \< 2.5 x the upper normal limits (\< 5 x the upper normal limit in the presence of hepatic metastasis)
* Creatinine \< 1.5 x the upper normal limit
* Adequate method of contraception (male and female), when there is risk of conception.

Exclusion Criteria:

* Symptomatic cerebral metastasis
* Previous chemotherapy for advanced disease
* Adjuvant chemotherapy within the previous 6 months
* Radiation therapy within previous 4 weeks
* Any experimental drug therapy within the previous 4 weeks
* Previous exposure to monoclonal antibodies, signal transduction inhibitors or EGFR targeting therapy
* Clinically relevant cardiopathy or myocardial infarct within the last 12 months
* Acute or subacute intestinal occlusion or history of inflammatory bowel disease
* Known allergy to one or more of the experimental treatments
* Known alcohol or substance abuse
* Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or give informed consent
* Pregnant or breastfeeding females
* History of malignant neoplasm within the previous 5 years (not including non-melanoma skin carcinoma and in-situ carcinoma of the uterine cervix, provided they are being adequately treated)

Primary outcomes:
measure: one year survival rate
timeFrame: one year
Secondary outcomes:
measure: toxicity
timeFrame: weekly
measure: overall survival
timeFrame: 18 months
measure: overall response rate
timeFrame: one year
measure: prognostic role of cetuximab associated skin toxicities
timeFrame: one year
Other outcomes:
Locations:
city: Monteforte Irpino
country: Italy
facility: Azienda Sanitaria S. Giuseppe Moscati
state: AV
city: Campobasso
country: Italy
facility: Ospedale A. Cardarelli
state: CB
city: Chieti
country: Italy
facility: Università di Chieti
state: CH
city: Frosinone
country: Italy
facility: Ospedale Umberto di Frosinone
state: FR
city: Genova
country: Italy
facility: Ospedale Villa Scassi
state: GE
city: Gaeta
country: Italy
facility: Ospedale di Gaeta
state: LT
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico G. Martino
state: ME
city: Milano
country: Italy
facility: Ospedale S. Giuseppe
state: MI
city: Milano
country: Italy
facility: Istituto Scientifico S. Raffaele
state: MI
city: Milano
country: Italy
facility: Ospedale S. Paolo
state: MI
city: Monza
country: Italy
facility: Ospedale S. Gerado
state: MI
city: Mantova
country: Italy
facility: Azienda Ospedaliera C. Poma
state: MN
city: Palermo
country: Italy
facility: Policlinico Giaccone
state: PA
city: Prato
country: Italy
facility: Ospedale di Prato
state: PO
city: Fano
country: Italy
facility: Ospedale S. Croce
state: PS
city: Pesaro
country: Italy
facility: Ospedale S. Salvatore
state: PU
city: Nocera Inferiore
country: Italy
facility: Ospedale Civile Umberto I
state: SA
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese
state: SI
city: Sondalo
country: Italy
facility: Ospedale E. Morelli
state: SO
city: Arco
country: Italy
facility: Presidio Ospedaliaro Alto Gardo e Ledro
state: TN
city: Trento
country: Italy
facility: Ospedale S. Chiara
state: TN
city: Saronno
country: Italy
facility: Azienda Ospedaliera Di Busto Arsizio
state: VA
city: Noale
country: Italy
facility: Divisione di Oncologia Medica, U.S.L.L. 13
state: VE
city: Napoli
country: Italy
facility: Azienda Ospedaliera Cardarelli
city: Napoli
country: Italy
facility: Second University of Naples
Study officials:
affiliation: S.G. Moscati Hopital, Avellino, Italy, Division of Medical Oncology
name: Cesare Gridelli, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Univesity of Naples, Italy; Chair Medical Oncology
name: Fortunato Ciardiello, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute Naples, Italy; Director Clinical Trials Unit
name: Francesco Perrone, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Second University of Naples, Italy; Chair of Medical Statistics
name: Ciro Gallo, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gridelli D, Mencoboni M, Carrozza F, Viganò MG, Gebbia V, Verusio C, Maione P, Gallo C, Perrone F, Ciardiello F. Cetuximab (C) and gemcitabine (G) in elderly or adult PS2 advanced non small-cell lung cancer (NSCLC) patients (pts): The CALC1 randomised phase II trials. Journal of Clinical Oncology 26: 2008 (May 20 suppl; abstr 8117)
citation: Gridelli C, Morabito A, Gebbia V, Mencoboni M, Carrozza F, Vigano MG, Verusio C, Bollina R, Mattioli R, Valerio MR, Valmadre G, Maione P, Rossi A, Cascone T, Morgillo F, Di Maio M, Piccirillo MC, Gallo C, Perrone F, Ciardiello F. Cetuximab and gemcitabine in elderly or adult PS2 patients with advanced non-small-cell lung cancer: The cetuximab in advanced lung cancer (CALC1-E and CALC1-PS2) randomized phase II trials. Lung Cancer. 2010 Jan;67(1):86-92. doi: 10.1016/j.lungcan.2009.03.021.