Clinical trial NCT01379976: Acetyl-L-carnitine in Combination With a Cisplatin-containing Chemotherapy as First Line Treatment of Advanced or Metastatic Non Small Cell Lung Cancer
Official title: Randomized, Double-blind, Placebo-controlled Phase 3 Trial to Assess the Efficacy and Safety of Acetyl-L-carnitine in Combination With a Cisplatin-containing Chemotherapy as First Line Treatment of Advanced or Metastatic Non Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Non Small Cell Lung Cancer
Keywords: lung
cancer
non small cell lung cancer
Advanced or metastatic non small cell lung cancer
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
First posted: 2011-06-23
Enrollment: 107
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: Study objectives Primary: To compare toxicity free survival of patients treated with ALC (acetylcarnitine) plus cisplatin-containing chemotherapy (CHT) versus those treated with placebo plus cisplatin-containing chemotherapy.

Secondary: To compare progression free survival, overall survival, the compliance to treatment, the number of episodes of grade 3-4 National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, neurotoxicity, as well as the proportion of patients experiencing grade 2-3-4 National Cancer Institute Common Terminology Criteria for Adverse Events, neuropathic pain intensity, the clinical signs and/or symptoms (such as burning, numbness, itching, etc.) of the sensorial neuropathy between the two treatment arms. Study design Multicentre, randomised, double-blind, placebo-controlled, phase III, superiority study in patients with advanced or metastatic NSCLC (non small cell lung cancer).

Patients to be screened for study inclusion are those for which the decision to start a cisplatin-containing treatment has been already taken in the context of the clinical practice. The type of cisplatin-based treatment is not fixed, but each single investigator is free to choose for each single patient among those already approved for first line treatment of advanced or metastatic NSCLC.

Patients meeting the eligibility criteria will be randomized with a 1 : 1 ratio to receive ALC + cisplatin-containing CHT or Placebo + cisplatin-containing CHT until patient refusal, disease progression, unacceptable toxicity or death. The study will be conducted in Italy in approximately 20 investigational centers in order to recruit 650-675 subjects over a 30-month period.

Both efficacy and safety data will be collected. Follow-up will be according to the clinical practice. Data capture will continue, for each patient, until death or study closure.

Detailed description: Inclusion criteria:

* Male or female \>= 18
* No previous CHT or targeted therapies. Previous adjuvant or neo-adjuvant treatment is permitted if completed ≥ 6 months before study inclusion.
* ECOG performance status 0-1
* Adequate organ functions defined as follows:
* 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
* Written informed consent given before the randomization, according to International Conference on Harmonization/Good Clinical Practice (ICH/GCP)

Exclusion criteria:

* Symptomatic brain metastases
* Any investigational agent(s) within 4 weeks prior to study entry
* Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months
* Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease
* Patients with known allergy to any other components of the study drugs
* History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complication
* 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
* Clinically relevant peripheral neuropathy
* 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)
* Pregnancy or breast feeding. Women of childbearing potential and their parents must be willing to practice acceptable methods of birth control to prevent pregnancy
* Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Eligibility criteria: Inclusion Criteria:

* Male or female ≥ 18
* No previous CHT or targeted therapies. Previous adjuvant or neo-adjuvant treatment is permitted if completed ≥ 6 months before study inclusion.
* ECOG performance status 0-1
* Adequate organ functions defined as follows:
* 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
* Written informed consent given before the randomization, according to International Conference on Harmonization/Good Clinical Practice (ICH/GCP)

Exclusion Criteria:

* Symptomatic brain metastases
* Any investigational agent(s) within 4 weeks prior to study entry
* Clinically relevant coronary artery disease or a history of a myocardial infarction within the last 12 months
* Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease
* Patients with known allergy to any other components of the study drugs
* History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complication
* 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
* Clinically relevant peripheral neuropathy
* 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)
* Pregnancy or breast feeding. Women of childbearing potential and their parents must be willing to practice acceptable methods of birth control to prevent pregnancy
* Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Primary outcomes:
measure: Toxicity Free Survival
timeFrame: participants will be followed for the duration of chemotherapy and for at least 1 yaer after the completation of treatment, an expected average of 18 months
Secondary outcomes:
measure: Progression-free survival
timeFrame: participants will be followed for the duration of chemotherapy and for at least 1 yaer after the completation of treatment, an expected average of 18 months
measure: Overall survival
timeFrame: participants will be followed for the duration of chemotherapy and for at least 1 yaer after the completation of treatment, an expected average of 18 months
measure: Neuropathic pain
timeFrame: participants will be followed for the duration of chemotherapy and for at least 1 yaer after the completation of treatment, an expected average of 18 months
Other outcomes:
Locations:
city: Viagrande
country: Italy
facility: Istituto Oncologico del Mediterraneo
state: CT
city: Como
country: Italy
facility: Azienda Ospedaliera Ospedale S. Anna
city: Cremona
country: Italy
facility: Azienda Ospedaliera Istituti Ospitalieri
city: Desio
country: Italy
facility: Azienda Ospedaliera di Desio e Vimercate - Presidio Ospedaliero di Desio
city: Guastalla
country: Italy
facility: Ospedale Civile
city: Lecco
country: Italy
facility: Ospedale Alessandro Manzoni
city: Legnano
country: Italy
facility: Azienda Ospedaliera Ospedale Civile di Legnano
city: Milano
country: Italy
facility: Azienda Ospedaliera Fatebenefratelli e Oftalmico
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
city: Milano
country: Italy
facility: Azienda Ospedaliera San Paolo
city: Milano
country: Italy
facility: Azienda Ospedaliera Ospedale San Carlo Borromeo
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri
city: Perugia
country: Italy
facility: Azienda Ospedaliera Perugia
city: Reggio Emilia
country: Italy
facility: Arcispedale S. Maria Nuova
city: Reggio Emilia
country: Italy
facility: IRCCS di Reggio Emilia
city: Saronno
country: Italy
facility: Azienda Ospedaliera Busto Arsizio - Presidio Ospedaliero di Saronno
city: Sassari
country: Italy
facility: Ospedale SS Annunziata - ASL1
city: Sondrio
country: Italy
facility: Azienda Ospedaliera Valtellina e Valchiavenna , Presidio Ospedaliero di Sondrio
city: Vigevano
country: Italy
facility: Azienda Ospedaliera di Pavia, Ospedale Civile di Vigevano
city: Vimercate
country: Italy
facility: Azienda Ospedaliera di Desio e Vimercate - Presidio Ospedaliero di Vimercate
Study officials:
affiliation: Azienda Ospedaliera di Perugia
name: Lucio Crinò, MD
role: PRINCIPAL_INVESTIGATOR
References: