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

NCT01379976 | Terminated Phase 3 DMC

• 1 other identifier: 2010-022021-15
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 21

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.

Conditions

Non Small Cell Lung Cancer

Keywords

lung; cancer; non small cell lung cancer; Advanced or metastatic non small cell lung cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Progression-free survival

  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

  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

  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

Study Arms (2)

CHT cisplatin containing + placebo

PLACEBO COMPARATOR

Drug: Placebo

CHT cisplatin containing + acetyl-L-carnitina

EXPERIMENTAL

Drug: Acetylcarnitine

Interventions

Acetylcarnitine 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.

Also known as: ST 200

CHT cisplatin containing + acetyl-L-carnitina

Placebo 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 + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 18
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (21)

Istituto Oncologico del Mediterraneo

Viagrande, CT, 95029, Italy

Location

Azienda Ospedaliera Ospedale S. Anna

Como, 22020, Italy

Location

Azienda Ospedaliera Istituti Ospitalieri

Cremona, 26100, Italy

Location

Azienda Ospedaliera di Desio e Vimercate - Presidio Ospedaliero di Desio

Desio, 20832, Italy

Location

Ospedale Civile

Guastalla, 42016, Italy

Location

Ospedale Alessandro Manzoni

Lecco, 23900, Italy

Location

Azienda Ospedaliera Ospedale Civile di Legnano

Legnano, 20025, Italy

Location

Azienda Ospedaliera Fatebenefratelli e Oftalmico

Milan, 20121, Italy

Location

Istituto Europeo Di Oncologia

Milan, 20141, Italy

Location

Azienda Ospedaliera San Paolo

Milan, 20142, Italy

Location

Azienda Ospedaliera Ospedale San Carlo Borromeo

Milan, 20153, Italy

Location

Azienda Ospedaliero Universitaria di Parma

Parma, 43126, Italy

Location

Fondazione Salvatore Maugeri

Pavia, 0381 33329, Italy

Location

Azienda Ospedaliera Perugia

Perugia, 06075, Italy

Location

Arcispedale S. Maria Nuova

Reggio Emilia, 42100, Italy

Location

IRCCS di Reggio Emilia

Reggio Emilia, 42123, Italy

Location

Azienda Ospedaliera Busto Arsizio - Presidio Ospedaliero di Saronno

Saronno, 21047, Italy

Location

Ospedale SS Annunziata - ASL1

Sassari, 07100, Italy

Location

Azienda Ospedaliera Valtellina e Valchiavenna , Presidio Ospedaliero di Sondrio

Sondrio, 23100, Italy

Location

Azienda Ospedaliera di Pavia, Ospedale Civile di Vigevano

Vigevano, 27029, Italy

Location

Azienda Ospedaliera di Desio e Vimercate - Presidio Ospedaliero di Vimercate

Vimercate, 20059, Italy

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

Acetylcarnitine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Carnitine; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals

Study Officials

• Lucio Crinò, MD

  Azienda Ospedaliera di Perugia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2011
• First Posted: June 23, 2011
• Study Start: April 1, 2011
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: April 24, 2015

Record last verified: 2014-07

Locations

IT (21)