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

Non Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01379976
• Other study ID #: 2010-022021-15
• Status: Terminated
• Phase: Phase 3
• First received: June 16, 2011
• Last updated: April 23, 2015
• Start date: April 2011
• Est. completion date: October 2014

Study information

• Verified date: July 2014
• Source: Mario Negri Institute for Pharmacological Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics CommitteeItaly: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 107
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

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.
• 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.

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera Ospedale S. Anna	Como
Italy	Azienda Ospedaliera Istituti Ospitalieri	Cremona
Italy	Azienda Ospedaliera di Desio e Vimercate - Presidio Ospedaliero di Desio	Desio
Italy	Ospedale Civile	Guastalla
Italy	Ospedale Alessandro Manzoni	Lecco
Italy	Azienda Ospedaliera Ospedale Civile di Legnano	Legnano
Italy	Azienda Ospedaliera Fatebenefratelli e Oftalmico	Milano
Italy	Azienda Ospedaliera Ospedale San Carlo Borromeo	Milano
Italy	Azienda Ospedaliera San Paolo	Milano
Italy	Istituto Europeo Di Oncologia	Milano
Italy	Azienda Ospedaliero Universitaria di Parma	Parma
Italy	Fondazione Salvatore Maugeri	Pavia
Italy	Azienda Ospedaliera Perugia	Perugia
Italy	Arcispedale S. Maria Nuova	Reggio Emilia
Italy	IRCCS di Reggio Emilia	Reggio Emilia
Italy	Azienda Ospedaliera Busto Arsizio - Presidio Ospedaliero di Saronno	Saronno
Italy	Ospedale SS Annunziata - ASL1	Sassari
Italy	Azienda Ospedaliera Valtellina e Valchiavenna , Presidio Ospedaliero di Sondrio	Sondrio
Italy	Istituto Oncologico del Mediterraneo	Viagrande	CT
Italy	Azienda Ospedaliera di Pavia, Ospedale Civile di Vigevano	Vigevano
Italy	Azienda Ospedaliera di Desio e Vimercate - Presidio Ospedaliero di Vimercate	Vimercate

Sponsors (1)

Lead Sponsor	Collaborator
Mario Negri Institute for Pharmacological Research

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No