Immunotherapy With Racotumomab in Advanced Lung Cancer
- Conditions
- NSCLCLung Cancer, Non-small Cell
- Interventions
- Biological: RacotumomabOther: Best Support Treatment
- Registration Number
- NCT01460472
- Lead Sponsor
- Recombio SL
- Brief Summary
This is a prospective, randomized, open label, parallel-group, multicenter phase III study to evaluate the efficacy and safety of active specific immunotherapy with racotumomab plus best supportive care versus best supportive care in patients with advanced NSCLC who have achieved an Objective Response (Partial or Complete Response) or Stable Disease with standard first-line treatment. Also immunological parameters will be evaluated. Best supportive therapy will be administered to all patients in the study according to institutional standards and includes any subsequent onco-specific therapies. 1082 patients will be included in the study, with non-small cell lung cancer in stages IIIA (non-resectable), IIIB or IV.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 1082
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Voluntarily signed informed consent.
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Cytologic or histologically diagnosed NSCLC in stages IIIA (non-resectable) or IIIB or IV (TNM).
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In continuous complete or partial remission or stable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) after standard first-line treatment.
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Imaging studies documenting the response to first-line therapy must be available for evaluation by the investigator.
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Time lapse of 21 to 56 days between the end of onco-specific treatment and start of vaccination. Patients must have recovered from any acute toxicity produced by previous therapy.
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Age greater than or equal to 18 years, either sex.
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Eastern Cooperative Oncology Group performance status less than 2.
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Adequate organ function, defined as follows:
8.1. Electrocardiogram (ECG) without significant anomalies, performed in the 7 days preceding entry
8.2. Haemoglobin greater than or equal to 90 g/L
8.3. Total white blood cell count (WBC) greater than or equal to 3.0 x 10^9/L
8.4. Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L
8.5. Platelet count greater than 100 x 10^9/L
8.6. Total bilirubin less than or equal to 1.5 fold the maximum normal value at the place of evaluation or 2.5 fold the maximum normal value in case of liver metastases
8.7. Glutamic-oxaloacetic transaminase/aspartate aminotransferase (GOT/AST), and glutamic-pyruvic transaminase/alanine aminotransferase (GPT/ALT), less than or equal to 2.5 fold the maximum normal value at the place of evaluation (in case of liver metastasis, less than 5 fold the maximum normal value)
8.8. Creatinine less than or equal to 2 mg/dL (less than or equal to 176 µmol/L)
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Known hepatitis B virus carriers who have liver function tests within the accepted limits are eligible
- Pregnant or breastfeeding patients
- Known hypersensitivity to any component of the formulation
- Fertile patients of either sex who do not use adequate contraceptive methods while on treatment
- Disease progression prior to randomization
- Recurrent NSCLC, who relapse less than one year after completing curative intent therapy
- Patients receiving other investigational medication (including investigational immunotherapy for NSCLC) or having received such medication within 30 days before entering the protocol
- Autoimmune diseases or chronic decompensated diseases
- Acute allergic disorders or a history of severe allergic reactions
- Known brain metastases
- History of demyelinating disease or inflammatory disease of the central nervous system or the peripheral nervous system
- Non-controlled intercurrent diseases, including active infections, symptomatic congestive heart failure, unstable chest angina or heart arrhythmia, as well as mentally incapable patients
- Other malignant diseases except non- melanoma skin cancer, in situ carcinoma of the cervix, incidental prostate cancer (T1a, Gleason less than or equal to 6, prostate specific antigen (PSA) less than 0.5 ng/ml) or any other tumour having received adequate treatment and evidencing a disease-free period greater than or equal to 5 years
- Receiving chronic therapy for more than 10 days at doses of prednisone greater than 10 mg/day (or equivalent) at the moment of the inclusion. Inhaled and topical corticosteroids are allowed.
- Active hepatitis C or positive tests for human immunodeficiency virus (HIV)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Racotumomab plus Best Support Treatment Racotumomab Patients will receive Racotumomab and Best Support Treatment, which includes any further onco-specific therapy for progressive disease. Best Support Treatment Best Support Treatment Patients will receive best support treatment for advanced NSCLC including onco-specific therapies when disease progresses.
- Primary Outcome Measures
Name Time Method Overall Survival Until date of death or last censored observation, on average upto 17 months A comparison of survival in the subgroup of inoperable stage IIIA and dry IIIB will be performed in 757 (approximately 70% of the study population)
- Secondary Outcome Measures
Name Time Method Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Best Support Treatment Group. Month 4 Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Best Support Treatment Group. Month 4 Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Racotumomab Group After the first year, every 3 months, on average for 17 months Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Racotumomab Group. Month 12 Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) Baseline Number of Participants with Adverse events as a measure of safety and tolerability Until death, on average during 17 months Safety will be evaluated at each study visit according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 and will include physical examination with vital signs, performance status as per the Eastern Cooperative Oncology Group scale(ECOG scale), laboratory tests and clinical history.
Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside Baseline Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay. Baseline Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Racotumomab Group Month 12 Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Best Support Treatment Group Month 4 Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry. Baseline Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Racotumomab Group. Month 12 Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Racotumomab Group. Month 12 Progression Free Survival From randomization until date of first documented progression of disease, assessed as per RECIST 1.0 during an expected average of 17 months Tumour evaluations will be performed every 2 months and evaluated as per Response Evaluation Criteria in Solid Tumors (RECIST).
Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Best Support Treatment Group Month 4 Evaluation of the reactivity if the antibodies against X63 tumor line (mouse yeloma) for Racotumomab Group Month 3 Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Best Support Treatment Group. Month 4 Measurement of pro-inflammatory and anti-inflammatory cytokines Baseline Determination of anti-idiotypic IgG response in the Racotumomab Group. Month 12 Measurement of pro-inflammatory and anti-inflammatory cytokines in the Racotumomab Group Month 12 Measurement of pro-inflammatory and anti-inflammatory cytokines in the Best Support Treatment Group Month 4 Determination of anti-idiotypic IgG response Baseline Determination of anti-idiotypic IgG response in the Best Support Treatment Group. Month 4
Trial Locations
- Locations (38)
Hospital "Celestino Hernández Robau"
🇨🇺Provincia de Villa Clara, Cuba
Veterans Memorial Medical Center
🇵🇭Manila, Philippines
Policlínica Privada Instituto de Medicina Nuclear
🇦🇷Bahía Blanca, Argentina
Instituto Oncológico de Córdoba
🇦🇷Córdoba, Argentina
Hospital Privado de Córdoba
🇦🇷Córdoba, Argentina
Hospital Italiano
🇦🇷Córdoba, Argentina
CRIO - Centro Regional Integrado de Oncologia
🇧🇷Fortaleza - CE, Brazil
Fundación COIR
🇦🇷Mendoza, Argentina
Centro Oncológico de Rosario
🇦🇷Rosario, Argentina
Hospital "Hermanos Ameijeiras"
🇨🇺Havana, Cuba
Dr Moewardi Hospital
🇮🇩Central Java, Indonesia
RS Kanker 'Dharmais'
🇮🇩Jakarta, Indonesia
Persahabatan Hospital
🇮🇩Jakarta, Indonesia
NOB - Nucleo de Oncologia da Bahia
🇧🇷Salvador - BA, Brazil
Dr Soetomo Hospital
🇮🇩Surabaya, Indonesia
HCPA - Hospital de Clínicas de Porto Alegre
🇧🇷Porto Alegre - RS, Brazil
Hospital de Base de São José do Rio Preto
🇧🇷São José do Rio Preto, Brazil
Hospital Amaral de Carvalho
🇧🇷Jau, Brazil
Centro Oncologico de Mogi das Cruzes
🇧🇷Mogi das Cruzes, Brazil
Faculdade de Medicina do ABC
🇧🇷Santo Andre, Brazil
Oncologistas Associados
🇧🇷Rio de Janeiro, Brazil
Hospital Jose Ramon Lopez Tabranes
🇨🇺Versalles, Cuba
Dr Sardjito Hospital
🇮🇩Yogyakarta, Indonesia
Perpetual Succour Hospital
🇵🇭Cebu City, Philippines
Johns Hopkins Singapore International Medical Centre
🇸🇬Singapore, Singapore
UPCO - Unidade de Pesquisas Clínicas em Oncologia
🇧🇷Pelotas - RS, Brazil
Hospital Moinhos de Vento
🇧🇷Porto Alegre, Brazil
Hospital Universitário de Brasília
🇧🇷Brasília - DF, Brazil
Pro Onco - Centro de Tratamento Oncológico
🇧🇷Londrina - PR, Brazil
Centro de Oncologia do Parana
🇧🇷Curitiba, Brazil
Liga Norte Riograndense Contra o Cancer
🇧🇷Natal, Brazil
GRAM - Grupo de Assistencia Medica e Prestacao de Servicos
🇧🇷Sao Paulo, Brazil
ISIS Clinica Especializada
🇦🇷Santa Fe, Argentina
Hospital da Cidade de Passo Fundo
🇧🇷Passo Fundo - RS, Brazil
Chiang Mai Hospital
🇹🇭Chiang Mai, Thailand
Khon Kaen Hospital, Division of Pulmonary and Critical Care Medicine
🇹🇭Khon Kaen, Thailand
Songklanagarind Hospital - HOCC-PSU
🇹🇭Songkhla, Thailand
Instituto Médico CER
🇦🇷Quilmes, Buenos Aires, Argentina