Clinical trial NCT01460472: Immunotherapy With Racotumomab in Advanced Lung Cancer
Official title: A Prospective, Randomized, Multicenter, Open Label Phase III Study of Active Specific Immunotherapy With Racotumomab Plus Best Support Treatment Versus Best Support Treatment in Patients With Advanced Non-small Cell Lung Camcer.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: NSCLC
Lung Cancer, Non-small Cell
Keywords: NSCLC
Lung cancer, small-cell
advanced lung cancer
therapeutic vaccine
anti-idiotypic vaccine
1E10
Lead sponsor: Recombio SL
Sponsor class: INDUSTRY
Collaborators: name: CIMAB (Cuba)
name: Laboratorio Elea Phoenix S.A.
name: Innogene Kalbiotech Pte. Ltd
name: Eurofarma Laboratorios S.A.
First posted: 2011-10-26
Enrollment: 1082
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Voluntarily signed informed consent.
2. Cytologic or histologically diagnosed NSCLC in stages IIIA (non-resectable) or IIIB or IV (TNM).
3. In continuous complete or partial remission or stable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) after standard first-line treatment.
4. Imaging studies documenting the response to first-line therapy must be available for evaluation by the investigator.
5. 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.
6. Age greater than or equal to 18 years, either sex.
7. Eastern Cooperative Oncology Group performance status less than 2.
8. 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)
9. Known hepatitis B virus carriers who have liver function tests within the accepted limits are eligible

Exclusion Criteria:

1. Pregnant or breastfeeding patients
2. Known hypersensitivity to any component of the formulation
3. Fertile patients of either sex who do not use adequate contraceptive methods while on treatment
4. Disease progression prior to randomization
5. Recurrent NSCLC, who relapse less than one year after completing curative intent therapy
6. Patients receiving other investigational medication (including investigational immunotherapy for NSCLC) or having received such medication within 30 days before entering the protocol
7. Autoimmune diseases or chronic decompensated diseases
8. Acute allergic disorders or a history of severe allergic reactions
9. Known brain metastases
10. History of demyelinating disease or inflammatory disease of the central nervous system or the peripheral nervous system
11. Non-controlled intercurrent diseases, including active infections, symptomatic congestive heart failure, unstable chest angina or heart arrhythmia, as well as mentally incapable patients
12. 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
13. 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.
14. Active hepatitis C or positive tests for human immunodeficiency virus (HIV)

Primary outcomes:
measure: Overall Survival
timeFrame: Until date of death or last censored observation, on average upto 17 months
Secondary outcomes:
measure: Number of Participants with Adverse events as a measure of safety and tolerability
timeFrame: Until death, on average during 17 months
measure: Progression Free Survival
timeFrame: From randomization until date of first documented progression of disease, assessed as per RECIST 1.0 during an expected average of 17 months
measure: Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside
timeFrame: Baseline
measure: Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Racotumomab Group
timeFrame: Month 3
measure: Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Racotumomab Group
timeFrame: Month 6
measure: Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Racotumomab Group
timeFrame: Month 9
measure: Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Racotumomab Group
timeFrame: Month 12
measure: Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Racotumomab Group
timeFrame: After the first year, every 3 months, on average for 17 months
measure: Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay.
timeFrame: Baseline
measure: Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Racotumomab Group.
timeFrame: Month 3
measure: Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Racotumomab Group.
timeFrame: Month 6
measure: Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Racotumomab Group.
timeFrame: Month 9
measure: Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Racotumomab Group.
timeFrame: Month 12
measure: Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Racotumomab Group
timeFrame: Baseline
measure: Evaluation of the reactivity if the antibodies against X63 tumor line (mouse yeloma) for Racotumomab Group
timeFrame: Month 3
measure: Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Racotumomab Group
timeFrame: Month 6
measure: Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Racotumomab Group
timeFrame: Month 9
measure: Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Racotumomab Group
timeFrame: Month 12
measure: Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Best Support Treatment Group
timeFrame: Baseline
measure: Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Best Support Treatment Group
timeFrame: Month 4
measure: Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Best Support Treatment Group
timeFrame: Baseline
measure: Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Best Support Treatment Group
timeFrame: Month 4
measure: Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Best Support Treatment Group.
timeFrame: Month 4
measure: Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry.
timeFrame: Baseline
measure: Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Racotumomab Group.
timeFrame: Month 3
measure: Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Racotumomab Group.
timeFrame: Month 6
measure: Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Racotumomab Group.
timeFrame: Month 9
measure: Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Racotumomab Group.
timeFrame: Month 12
measure: Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Best Support Treatment Group.
timeFrame: Month 4
measure: Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available)
timeFrame: Baseline
measure: Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Racotumomab Group.
timeFrame: Month 3
measure: Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Racotumomab Group.
timeFrame: Month 6
measure: Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Racotumomab Group.
timeFrame: Month 9
measure: Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Racotumomab Group.
timeFrame: Month 12
measure: Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Best Support Treatment Group.
timeFrame: Month 4
measure: Measurement of pro-inflammatory and anti-inflammatory cytokines
timeFrame: Baseline
measure: Measurement of pro-inflammatory and anti-inflammatory cytokines in the Racotumomab Group
timeFrame: Month 3
measure: Measurement of pro-inflammatory and anti-inflammatory cytokines in the Racotumomab Group
timeFrame: Month 6
measure: Measurement of pro-inflammatory and anti-inflammatory cytokines in the Racotumomab Group
timeFrame: Month 9
measure: Measurement of pro-inflammatory and anti-inflammatory cytokines in the Racotumomab Group
timeFrame: Month 12
measure: Measurement of pro-inflammatory and anti-inflammatory cytokines in the Best Support Treatment Group
timeFrame: Month 4
measure: Determination of anti-idiotypic IgG response
timeFrame: Baseline
measure: Determination of anti-idiotypic IgG response in the Racotumomab Group.
timeFrame: Month 3
measure: Determination of anti-idiotypic IgG response in the Racotumomab Group.
timeFrame: Month 6
measure: Determination of anti-idiotypic IgG response in the Racotumomab Group.
timeFrame: Month 9
measure: Determination of anti-idiotypic IgG response in the Racotumomab Group.
timeFrame: Month 12
measure: Determination of anti-idiotypic IgG response in the Best Support Treatment Group.
timeFrame: Month 4
Other outcomes:
Locations:
city: Quilmes
country: Argentina
facility: Instituto Médico CER
state: Buenos Aires
city: Bahía Blanca
country: Argentina
facility: Policlínica Privada Instituto de Medicina Nuclear
city: Córdoba
country: Argentina
facility: Hospital Italiano
city: Córdoba
country: Argentina
facility: Hospital Privado de Córdoba
city: Córdoba
country: Argentina
facility: Instituto Oncológico de Córdoba
city: Mendoza
country: Argentina
facility: Fundación COIR
city: Rosario
country: Argentina
facility: Centro Oncológico de Rosario
city: Santa Fe
country: Argentina
facility: ISIS Clinica Especializada
city: Salvador
country: Brazil
facility: NOB - Nucleo de Oncologia da Bahia
state: BA
city: Fortaleza
country: Brazil
facility: CRIO - Centro Regional Integrado de Oncologia
state: CE
city: Brasília
country: Brazil
facility: Hospital Universitário de Brasília
state: DF
city: Londrina
country: Brazil
facility: Pro Onco - Centro de Tratamento Oncológico
state: PR
city: Passo Fundo
country: Brazil
facility: Hospital da Cidade de Passo Fundo
state: RS
city: Pelotas
country: Brazil
facility: UPCO - Unidade de Pesquisas Clínicas em Oncologia
state: RS
city: Porto Alegre
country: Brazil
facility: HCPA - Hospital de Clínicas de Porto Alegre
state: RS
city: São José do Rio Preto
country: Brazil
facility: Hospital de Base de São José do Rio Preto
state: SP
city: Brasília - DF
country: Brazil
facility: Hospital Universitário de Brasília
city: Curitiba
country: Brazil
facility: Centro de Oncologia do Parana
city: Fortaleza - CE
country: Brazil
facility: CRIO - Centro Regional Integrado de Oncologia
city: Jau
country: Brazil
facility: Hospital Amaral de Carvalho
city: Londrina - PR
country: Brazil
facility: Pro Onco - Centro de Tratamento Oncológico
city: Mogi das Cruzes
country: Brazil
facility: Centro Oncologico de Mogi das Cruzes
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra o Cancer
city: Passo Fundo - RS
country: Brazil
facility: Hospital da Cidade de Passo Fundo
city: Pelotas - RS
country: Brazil
facility: UPCO - Unidade de Pesquisas Clínicas em Oncologia
city: Porto Alegre - RS
country: Brazil
facility: HCPA - Hospital de Clínicas de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Hospital Moinhos de Vento
city: Rio de Janeiro
country: Brazil
facility: Oncologistas Associados
city: Salvador - BA
country: Brazil
facility: NOB - Nucleo de Oncologia da Bahia
city: Santo Andre
country: Brazil
facility: Faculdade de Medicina do ABC
city: Sao Paulo
country: Brazil
facility: GRAM - Grupo de Assistencia Medica e Prestacao de Servicos
city: São José do Rio Preto
country: Brazil
facility: Hospital de Base de São José do Rio Preto
city: Havana
country: Cuba
facility: Hospital "Hermanos Ameijeiras"
city: Provincia de Villa Clara
country: Cuba
facility: Hospital "Celestino Hernández Robau"
city: Versalles
country: Cuba
facility: Hospital Jose Ramon Lopez Tabranes
city: Central Java
country: Indonesia
facility: Dr Moewardi Hospital
city: Jakarta
country: Indonesia
facility: Persahabatan Hospital
city: Jakarta
country: Indonesia
facility: RS Kanker 'Dharmais'
city: Surabaya
country: Indonesia
facility: Dr Soetomo Hospital
city: Yogyakarta
country: Indonesia
facility: Dr Sardjito Hospital
city: Cebu City
country: Philippines
facility: Perpetual Succour Hospital
city: Manila
country: Philippines
facility: Veterans Memorial Medical Center
city: Singapore
country: Singapore
facility: Johns Hopkins Singapore International Medical Centre
city: Chiang Mai
country: Thailand
facility: Chiang Mai Hospital
city: Khon Kaen
country: Thailand
facility: Khon Kaen Hospital, Division of Pulmonary and Critical Care Medicine
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital - HOCC-PSU
Study officials:
affiliation: Recombio S.L.
name: Roberto Gomez, M.D.
role: STUDY_DIRECTOR
References: