Immunotherapy With Racotumomab in Advanced Lung Cancer

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.

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.

Study Overview

• Status: Unknown
• Conditions: NSCLC; Lung Cancer, Non-small Cell
• Intervention / Treatment: Biological: Racotumomab; Other: Best Support Treatment

• Study Type: Interventional
• Enrollment (Anticipated): 1082
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Bahía Blanca, Argentina
    • Policlínica Privada Instituto de Medicina Nuclear
  • Córdoba, Argentina
    • Hospital Italiano
  • Córdoba, Argentina
    • Hospital Privado de Cordoba
  • Córdoba, Argentina
    • Instituto Oncologico de Cordoba
  • Mendoza, Argentina
    • Fundacion COIR
  • Rosario, Argentina
    • Centro Oncologico de Rosario
  • Santa Fe, Argentina
    • ISIS Clinica Especializada
  • Buenos Aires
    • Quilmes, Buenos Aires, Argentina
      • Instituto Médico CER
• Brazil
  • Brasília - DF, Brazil
    • Hospital Universitário de Brasília
  • Curitiba, Brazil
    • Centro de Oncologia do Parana
  • Fortaleza - CE, Brazil
    • Crio - Centro Regional Integrado de Oncologia
  • Jau, Brazil
    • Hospital Amaral de Carvalho
  • Londrina - PR, Brazil
    • Pro Onco - Centro de Tratamento Oncológico
  • Mogi das Cruzes, Brazil
    • Centro Oncológico de Mogi das Cruzes
  • Natal, Brazil
    • Liga Norte Riograndense Contra O Cancer
  • Passo Fundo - RS, Brazil
    • Hospital da Cidade de Passo Fundo
  • Pelotas - RS, Brazil
    • UPCO - Unidade de Pesquisas Clínicas em Oncologia
  • Porto Alegre, Brazil
    • Hospital Moinhos de Vento
  • Porto Alegre - RS, Brazil
    • HCPA - Hospital de Clínicas de Porto Alegre
  • Rio de Janeiro, Brazil
    • Oncologistas Associados
  • Salvador - BA, Brazil
    • Nob - Nucleo de Oncologia Da Bahia
  • Santo Andre, Brazil
    • Faculdade de Medicina do ABC
  • Sao Paulo, Brazil
    • GRAM - Grupo de Assistencia Medica e Prestacao de Servicos
  • São José do Rio Preto, Brazil
    • Hospital de Base de Sao Jose do Rio Preto
  • BA
    • Salvador, BA, Brazil
      • Nob - Nucleo de Oncologia Da Bahia
  • CE
    • Fortaleza, CE, Brazil
      • Crio - Centro Regional Integrado de Oncologia
  • DF
    • Brasília, DF, Brazil
      • Hospital Universitário de Brasília
  • PR
    • Londrina, PR, Brazil
      • Pro Onco - Centro de Tratamento Oncológico
  • RS
    • Passo Fundo, RS, Brazil
      • Hospital da Cidade de Passo Fundo
    • Pelotas, RS, Brazil
      • UPCO - Unidade de Pesquisas Clínicas em Oncologia
    • Porto Alegre, RS, Brazil
      • HCPA - Hospital de Clínicas de Porto Alegre
  • SP
    • São José do Rio Preto, SP, Brazil
      • Hospital de Base de Sao Jose do Rio Preto
• Cuba
  • Havana, Cuba
    • Hospital "Hermanos Ameijeiras"
  • Provincia de Villa Clara, Cuba
    • Hospital "Celestino Hernández Robau"
  • Versalles, Cuba
    • Hospital Jose Ramon Lopez Tabranes
• Indonesia
  • Central Java, Indonesia
    • Dr Moewardi Hospital
  • Jakarta, Indonesia
    • Persahabatan Hospital
  • Jakarta, Indonesia
    • RS Kanker 'Dharmais'
  • Surabaya, Indonesia
    • Dr Soetomo Hospital
  • Yogyakarta, Indonesia
    • Dr Sardjito Hospital
• Philippines
  • Cebu City, Philippines
    • Perpetual Succour Hospital
  • Manila, Philippines
    • Veterans Memorial Medical Center
• Singapore
  • Singapore, Singapore
    • Johns Hopkins Singapore International Medical Centre
• Thailand
  • Chiang Mai, Thailand
    • Chiang Mai Hospital
  • Khon Kaen, Thailand
    • Khon Kaen Hospital, Division of Pulmonary and Critical Care Medicine
  • Songkhla, Thailand
    • Songklanagarind Hospital - HOCC-PSU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Racotumomab plus Best Support Treatment; Patients will receive Racotumomab and Best Support Treatment, which includes any further onco-specific therapy for progressive disease.	Biological: Racotumomab; Patients will receive best support treatment and vaccination with racotumomab. The vaccination schedule is as follows: 5 doses (1mg/mL each), intradermally, every 2 weeks (induction period) followed by monthly vaccinations until any criteria for discontinuation are met. If disease progression occurs and further onco-specific therapy is indicated, the patient will be able to continue in the study and vaccination will not be interrupted unless criteria for vaccine discontinuation are met.; Other Names: 1E10
Active Comparator: Best Support Treatment; Patients will receive best support treatment for advanced NSCLC including onco-specific therapies when disease progresses.	Other: Best Support Treatment; Patients will receive best support treatment for advanced NSCLC as per each institution's standards, including onco-specific therapies when disease progresses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	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)	Until date of death or last censored observation, on average upto 17 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse events as a measure of safety and tolerability	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.	Until death, on average during 17 months
Progression Free Survival	Tumour evaluations will be performed every 2 months and evaluated as per Response Evaluation Criteria in Solid Tumors (RECIST).	From randomization until date of first documented progression of disease, assessed as per RECIST 1.0 during an expected average of 17 months
Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside		Baseline
Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Racotumomab Group		Month 3
Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Racotumomab Group		Month 6
Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Racotumomab Group		Month 9
Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Racotumomab Group		Month 12
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.		Baseline
Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Racotumomab Group.		Month 3
Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Racotumomab Group.		Month 6
Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Racotumomab Group.		Month 9
Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Racotumomab Group.		Month 12
Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Racotumomab Group		Baseline
Evaluation of the reactivity if the antibodies against X63 tumor line (mouse yeloma) for Racotumomab Group		Month 3
Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Racotumomab Group		Month 6
Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Racotumomab Group		Month 9
Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Racotumomab Group		Month 12
Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Best Support Treatment Group		Baseline
Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Best Support Treatment Group		Month 4
Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Best Support Treatment Group		Baseline
Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for 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 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 3
Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Racotumomab Group.		Month 6
Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Racotumomab Group.		Month 9
Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Racotumomab Group.		Month 12
Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Best Support Treatment Group.		Month 4
Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available)		Baseline
Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Racotumomab Group.		Month 3
Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Racotumomab Group.		Month 6
Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Racotumomab Group.		Month 9
Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Racotumomab Group.		Month 12
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
Measurement of pro-inflammatory and anti-inflammatory cytokines in the Racotumomab Group		Month 3
Measurement of pro-inflammatory and anti-inflammatory cytokines in the Racotumomab Group		Month 6
Measurement of pro-inflammatory and anti-inflammatory cytokines in the Racotumomab Group		Month 9
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 Racotumomab Group.		Month 3
Determination of anti-idiotypic IgG response in the Racotumomab Group.		Month 6
Determination of anti-idiotypic IgG response in the Racotumomab Group.		Month 9
Determination of anti-idiotypic IgG response in the Racotumomab Group.		Month 12
Determination of anti-idiotypic IgG response in the Best Support Treatment Group.		Month 4

Collaborators and Investigators

• Sponsor: Recombio SL
• Collaborators: Eurofarma Laboratorios S.A.; Laboratorio Elea Phoenix S.A.; Innogene Kalbiotech Pte. Ltd; CIMAB (Cuba)
• Investigators: Study Director: Roberto Gomez, M.D., Recombio S.L.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Anticipated): September 1, 2016
• Study Completion (Anticipated): September 1, 2016

Study Registration Dates

• First Submitted: October 23, 2011
• First Submitted That Met QC Criteria: October 24, 2011
• First Posted (Estimate): October 26, 2011

Study Record Updates

• Last Update Posted (Estimate): July 29, 2016
• Last Update Submitted That Met QC Criteria: July 28, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: NSCLC; advanced lung cancer; therapeutic vaccine; Lung cancer, small-cell; anti-idiotypic vaccine; 1E10
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: EC-AR-1E10 MAb-301; ISRCTN47153584 (REGISTRY: Intl Standard Randomised Controlled Trial Number Register)