Study to Evaluate Treatment Customized According to RAP80 and BRCA1 in Patients With Advanced Lung Carcinoma
Condition: Non Small Cell Lung Cancer; BRCA1 Mutation
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Cisplatin, Docetaxel; Gemcitabine, Cisplatin; Docetaxel, Cisplatin; Docetaxel
Intervention description: Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6; Gemcitabine 1250 mg/m2, days 1 and 8, and Cisplatin 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6; Docetaxel 75 mg/m2 and Cisplatin 75 mg/m2, both administered on day 1, every 21 days. Total number of cycles: 6; Docetaxel 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6
Intervention MeSH terms: Cisplatin; Gemcitabine; Docetaxel
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 382.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lung Cancer; Chemotherapy; Personalized medicine

Summary:

      Primary objective:

      · Progression free survival.

      Secondary objectives:

        -  Assess Overall survival of both treatment groups.

        -  Assess Tumor response rate using RECIST criteria

        -  Assess Toxicity profile of patients enrolled in the study.

        -  Exploratory evaluation of potential genetic markers of response or resistance to
           chemotherapy.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          1. Patients age 18 years or more.

          2. Histologically confirmed diagnosis of non-small-cell lung carcinoma.

          3. Only patients with advanced disease defined as stage IV or IIIB with or without
             pleural effusion will be included. In the event of IIIB disease without pleural
             effusion those patients, who for some reason (respiratory disease, large radiation
             volume...) may not be candidates to have chemotherapy and radiotherapy treatment and
             may only be treated with chemotherapy, will be considered.

          4. Tumor specimen available (according to the criterion of the specimen-processing
             laboratory) for the analysis of RAP80 and BRCA1 expression in mRNA.

          5. A measurable lesion, as defined by RECIST criteria.

          6. Karnofsky score 80% or more (ECOG < 2).

          7. No previous treatment with chemotherapy or other agents for disseminated disease.
             Chemotherapy is allowed if the patient's initial diagnosis is limited disease and the
             patient has received adjuvant or neoadjuvant treatment, as long as a minimum of 6
             months has passed since the end of the adjuvant and/or neo-adjuvant chemotherapy.

          8. Patients with cerebral disease may be included without any time limitations after
             holocranial irradiation or complementary antiedema treatment, as long as there is
             correct control of the clinical symptoms arising from the brain disease or is
             symptomatic.

          9. Patients with the following hematologic values:

             ANC ≥ 1.5 x 109/L Hb ≥ 10 g/dl Platelets ≥ 100 x 109/L

         10. Patients with the following biochemical values:

             Bilirubin ≤ 1.5 mg/dL AST and ALT < 1.5 upper limit of normality Creatinine clearance
             ≥ 60 ml/min.

         11. Patients of childbearing age of either sex must use effective contraceptive methods
             (barrier methods or other birth control methods) before entering the study and while
             participating in the study.

         12. Patients should sign an informed consent form before inclusion in the study that
             specifies that the clinical trial treatment entails consent for the analysis of
             biological specimens of tumor and blood.

         13. Patients must be available for clinical follow-up.

        EXCLUSION CRITERIA

          1. Previous chemotherapy treatment, except the supposition reflected in inclusion
             criterion 7.

          2. Patients diagnosed of another neoplasm, with the exception of cervical carcinoma in
             situ, treated squamous cell carcinomas or superficial bladder tumors (Ta and TIS), or
             other malignant tumors that have received curative treatment within the last 5 years
             before inclusion in the study.

          3. Patients with serious active bacterial or fungal infective processes from a clinical
             vantage point (= grade 2 of NCI-CTC, Version 3).

          4. Patients who have received an investigational medicinal product in the 21 days before
             inclusion in the study.

          5. Patients with HIV infection, HCV infection, coronary artery disease or uncontrolled
             arrhythmia, uncontrolled cerebrovascular disease, or other clinical conditions that,
             in the judgment of the investigator, contraindicate the patient's participation in the
             study.

          6. Patients who are pregnant or breastfeeding. Women of childbearing age must have a
             negative pregnancy test performed within 7 days before the onset of treatment.

          7. Substance abuse and clinical, psychological or social conditions that can undermine
             the validity of the informed consent or protocol compliance.

          8. Patients who present any contraindication or suspected allergy to the products under
             investigation in the study

          9. Impossibility to comply with chemotherapy treatment due to cultural or geographic
             circumstances.

         10. Significant weight loss (= 10% of body weight) in the 6 weeks before inclusion in the
             study.

         11. Any condition that is unstable or could endanger the patient's safety and/or the
             patient's compliance with the study.

         12. Contraindication for steroid use.