Acetyl-L-carnitine in Combination With a Cisplatin-containing Chemotherapy as First Line Treatment of Advanced or Metastatic Non Small Cell Lung Cancer

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 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.

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

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