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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier:
NCT01379976
First received: June 16, 2011
Last updated: June 20, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Non Small Cell Lung Cancer
Drug: Acetylcarnitine
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Mario Negri Institute for Pharmacological Research:

Primary Outcome Measures:
  • Toxicity Free Survival [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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

  • Overall survival [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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

  • Neuropathic pain [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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)


Estimated Enrollment: 675
Study Start Date: April 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: ST 200

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01379976

Locations
Italy
Istituto Oncologico del Mediterraneo
Viagrande, CT, Italy, 95029
Azienda Ospedaliera Ospedale S. Anna
Como, Italy, 22020
Azienda Ospedaliera Istituti Ospitalieri
Cremona, Italy, 26100
Azienda Ospedaliera di Desio e Vimercate - Presidio Ospedaliero di Desio
Desio, Italy, 20832
Ospedale Civile
Guastalla, Italy, 42016
Azienda Ospedaliera Ospedale Civile di Legnano
Legnano, Italy, 20025
Azienda Ospedaliera Fatebenefratelli e Oftalmico
Milano, Italy, 20121
Istituto Europeo Di Oncologia
Milano, Italy, 20141
Azienda Ospedaliera San Paolo
Milano, Italy, 20142
Azienda Ospedaliera Ospedale San Carlo Borromeo
Milano, Italy, 20153
Azienda Ospedaliero Universitaria di Parma
Parma, Italy, 43126
Fondazione Salvatore Maugeri
Pavia, Italy, 0381 33329
Azienda Ospedaliera Perugia
Perugia, Italy, 06075
IRCCS di Reggio Emilia
Reggio Emilia, Italy, 42123
Arcispedale S. Maria Nuova
Reggio Emilia, Italy, 42100
Azienda Ospedaliera Busto Arsizio - Presidio Ospedaliero di Saronno
Saronno, Italy, 21047
Azienda Ospedaliera Valtellina e Valchiavenna , Presidio Ospedaliero di Sondrio
Sondrio, Italy, 23100
Azienda Ospedaliera di Pavia, Ospedale Civile di Vigevano
Vigevano, Italy, 27029
Azienda Ospedaliera di Desio e Vimercate - Presidio Ospedaliero di Vimercate
Vimercate, Italy, 20059
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
Investigators
Principal Investigator: Lucio Crinò, MD Azienda Ospedaliera di Perugia
  More Information

No publications provided

Responsible Party: Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier: NCT01379976     History of Changes
Other Study ID Numbers: 2010-022021-15
Study First Received: June 16, 2011
Last Updated: June 20, 2013
Health Authority: Italy: Ethics Committee
Italy: The Italian Medicines Agency

Keywords provided by Mario Negri Institute for Pharmacological Research:
lung
cancer
non small cell lung cancer
Advanced or metastatic non small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Acetylcarnitine
Carnitine
Cisplatin
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on April 17, 2014