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

NCT ID: NCT01379976

Last Updated: 2015-04-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2014-10-31

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

Conditions

Non Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

CHT cisplatin containing + placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

CHT cisplatin containing + acetyl-L-carnitina

Group Type: EXPERIMENTAL

Acetylcarnitine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

ST 200

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mario Negri Institute for Pharmacological Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lucio Crinò, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliera di Perugia

Locations

Istituto Oncologico del Mediterraneo

Viagrande, CT, 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

Milan, , Italy

Istituto Europeo Di Oncologia

Milan, , Italy

Azienda Ospedaliera San Paolo

Milan, , Italy

Azienda Ospedaliera Ospedale San Carlo Borromeo

Milan, , 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

Azienda Ospedaliera di Pavia, Ospedale Civile di Vigevano

Vigevano, , Italy

Azienda Ospedaliera di Desio e Vimercate - Presidio Ospedaliero di Vimercate

Vimercate, , Italy

Countries

Italy

Other Identifiers

2010-022021-15

Identifier Type: -

Identifier Source: org_study_id