Immunotherapy With Racotumomab in Advanced Lung Cancer

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)