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.

Study Overview

• Status: Terminated
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Placebo; Drug: Acetylcarnitine

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

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Como, Italy, 22020
    • Azienda Ospedaliera Ospedale S. Anna
  • Cremona, Italy, 26100
    • Azienda Ospedaliera Istituti Ospitalieri
  • Desio, Italy, 20832
    • Azienda Ospedaliera di Desio e Vimercate - Presidio Ospedaliero di Desio
  • Guastalla, Italy, 42016
    • Ospedale Civile
  • Lecco, Italy, 23900
    • Ospedale Alessandro Manzoni
  • Legnano, Italy, 20025
    • Azienda Ospedaliera Ospedale Civile di Legnano
  • Milano, Italy, 20141
    • Istituto Europeo di Oncologia
  • Milano, Italy, 20121
    • Azienda Ospedaliera Fatebenefratelli e Oftalmico
  • Milano, Italy, 20153
    • Azienda Ospedaliera Ospedale San Carlo Borromeo
  • Milano, Italy, 20142
    • Azienda Ospedaliera San Paolo
  • Parma, Italy, 43126
    • Azienda Ospedaliero Universitaria di Parma
  • Pavia, Italy, 0381 33329
    • Fondazione Salvatore Maugeri
  • Perugia, Italy, 06075
    • Azienda ospedaliera Perugia
  • Reggio Emilia, Italy, 42100
    • Arcispedale S. Maria Nuova
  • Reggio Emilia, Italy, 42123
    • IRCCS di Reggio Emilia
  • Saronno, Italy, 21047
    • Azienda Ospedaliera Busto Arsizio - Presidio Ospedaliero di Saronno
  • Sassari, Italy, 07100
    • Ospedale SS Annunziata - ASL1
  • Sondrio, Italy, 23100
    • Azienda Ospedaliera Valtellina e Valchiavenna , Presidio Ospedaliero di Sondrio
  • Vigevano, Italy, 27029
    • Azienda Ospedaliera di Pavia, Ospedale Civile di Vigevano
  • Vimercate, Italy, 20059
    • Azienda Ospedaliera di Desio e Vimercate - Presidio Ospedaliero di Vimercate
  • CT
    • Viagrande, CT, Italy, 95029
      • Istituto Oncologico del Mediterraneo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: CHT cisplatin containing + placebo	Drug: Placebo; ALC or placebo will be administered concurrently with CHT at 1000 mg sachet three times every day (before meals). Treatment should be administered for a maximum of 6 cycles for both arms unless progression or unacceptable toxicity, or treatment refusal.
Experimental: CHT cisplatin containing + acetyl-L-carnitina	Drug: Acetylcarnitine; ALC or placebo will be administered concurrently with CHT at 1000 mg sachet three times every day (before meals). Treatment should be administered for a maximum of 6 cycles for both arms unless progression or unacceptable toxicity, or treatment refusal.; Other Names: ST 200

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity Free Survival	The primary efficacy endpoint is toxicity-free survival, defined as the time from randomisation up to the occurrence of related to treatment grade 2-3-4 NCI-CTCAE neurotoxicity, progression, second primary malignancy, death from any cause, whichever comes first. Subjects who have not experienced related to treatment grade 2-3-4 toxicity, and not progressed or died while on study will be censored at their last assessment date.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	defined as the time from randomisation up to the occurrence of progression, second primary malignancy, death from any cause, whichever comes first. Subjects who have not progressed or died while on study will be censored at their last assessment date	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
Overall survival	defined as the time from the date of randomisation to the date of death from any cause. Subjects not reported as having died at the end of the study will be censored at the date they were last known to be alive	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
Neuropathic pain	Occurrence of neuropathic pain is defined as the presence of at least 4 of the 10 clinical signs/symptoms listed in the DN4-Questionnaire Neuropathic pain intensity is defined as the intensity of pain reported by patients (current, average and worst during the last week) during scheduled visit as assessed by a self-administered questionnaire (BPI)	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

Collaborators and Investigators

• Sponsor: Mario Negri Institute for Pharmacological Research
• Investigators: Principal Investigator: Lucio Crinò, MD, Azienda Ospedaliera di Perugia

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: June 16, 2011
• First Submitted That Met QC Criteria: June 22, 2011
• First Posted (Estimate): June 23, 2011

Study Record Updates

• Last Update Posted (Estimate): April 24, 2015
• Last Update Submitted That Met QC Criteria: April 23, 2015
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: lung; cancer; non small cell lung cancer; Advanced or metastatic non small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Nootropic Agents; Acetylcarnitine
• Other Study ID Numbers: 2010-022021-15