Immunotherapy With Racotumomab in Advanced Lung Cancer

NSCLC Clinical Trial

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01460472
• Other study ID #: EC-AR-1E10 MAb-301
• Secondary ID: ISRCTN47153584
• Status: Active, not recruiting
• Phase: Phase 3
• First received: October 23, 2011
• Last updated: July 28, 2016
• Start date: September 2010
• Est. completion date: September 2016

Study information

• Verified date: July 2016
• Source: Recombio SL
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaBrazil: National Committee of Ethics in ResearchCuba: Ministry of Public HealthIndonesia:BPOM-Badan Pengawas Obat dan Makanan aka National Agency for Drug and Food ControlPhilippines: Bureau of Food and DrugsThailand:TFDA-Thailand Food and Drug AdministrationUruguay: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1082
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer, Non-small Cell
• Lung Neoplasms
• NSCLC

Intervention

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:
• 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.

Locations

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

Sponsors (5)

Lead Sponsor	Collaborator
Recombio SL	CIMAB (Cuba), Eurofarma Laboratorios S.A., Innogene Kalbiotech Pte. Ltd, Laboratorio Elea S.A.C.I.F. y A.

Countries where clinical trial is conducted

Argentina,  Brazil,  Cuba,  Indonesia,  Philippines,  Singapore,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside		Baseline	No
Secondary	Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Racotumomab Group		Month 3	No
Secondary	Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Racotumomab Group		Month 6	No
Secondary	Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Racotumomab Group		Month 9	No
Secondary	Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Racotumomab Group		Month 12	No
Secondary	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	No
Secondary	Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay.		Baseline	No
Secondary	Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Racotumomab Group.		Month 3	No
Secondary	Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Racotumomab Group.		Month 6	No
Secondary	Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Racotumomab Group.		Month 9	No
Secondary	Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Racotumomab Group.		Month 12	No
Secondary	Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Racotumomab Group		Baseline	No
Secondary	Evaluation of the reactivity if the antibodies against X63 tumor line (mouse yeloma) for Racotumomab Group		Month 3	No
Secondary	Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Racotumomab Group		Month 6	No
Secondary	Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Racotumomab Group		Month 9	No
Secondary	Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Racotumomab Group		Month 12	No
Secondary	Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Best Support Treatment Group		Baseline	No
Secondary	Evaluation of the reactivity if the antibodies against X63 tumor line (mouse myeloma) for Best Support Treatment Group		Month 4	No
Secondary	Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Best Support Treatment Group		Baseline	No
Secondary	Determination of IgM and IgG antibody titers against N-Glycolil-GM3 ganglioside for Best Support Treatment Group		Month 4	No
Secondary	Determination of gamma interferon by ELISPOT (enzyme-linked immunosorbent spot) assay for Best Support Treatment Group.		Month 4	No
Secondary	Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry.		Baseline	No
Secondary	Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Racotumomab Group.		Month 3	No
Secondary	Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Racotumomab Group.		Month 6	No
Secondary	Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Racotumomab Group.		Month 9	No
Secondary	Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Racotumomab Group.		Month 12	No
Secondary	Determination of T supressor cell (Treg cell) frequency by immunostaining and flow cytometry in the Best Support Treatment Group.		Month 4	No
Secondary	Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available)		Baseline	No
Secondary	Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Racotumomab Group.		Month 3	No
Secondary	Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Racotumomab Group.		Month 6	No
Secondary	Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Racotumomab Group.		Month 9	No
Secondary	Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Racotumomab Group.		Month 12	No
Secondary	Evaluation of the reactivity of the antibodies against the patients tumoral tissue (whenever samples are available) in the Best Support Treatment Group.		Month 4	No
Secondary	Measurement of pro-inflammatory and anti-inflammatory cytokines		Baseline	No
Secondary	Measurement of pro-inflammatory and anti-inflammatory cytokines in the Racotumomab Group		Month 3	No
Secondary	Measurement of pro-inflammatory and anti-inflammatory cytokines in the Racotumomab Group		Month 6	No
Secondary	Measurement of pro-inflammatory and anti-inflammatory cytokines in the Racotumomab Group		Month 9	No
Secondary	Measurement of pro-inflammatory and anti-inflammatory cytokines in the Racotumomab Group		Month 12	No
Secondary	Measurement of pro-inflammatory and anti-inflammatory cytokines in the Best Support Treatment Group		Month 4	No
Secondary	Determination of anti-idiotypic IgG response		Baseline	No
Secondary	Determination of anti-idiotypic IgG response in the Racotumomab Group.		Month 3	No
Secondary	Determination of anti-idiotypic IgG response in the Racotumomab Group.		Month 6	No
Secondary	Determination of anti-idiotypic IgG response in the Racotumomab Group.		Month 9	No
Secondary	Determination of anti-idiotypic IgG response in the Racotumomab Group.		Month 12	No
Secondary	Determination of anti-idiotypic IgG response in the Best Support Treatment Group.		Month 4	No