The 'MADe IT' Clinical Trial: Molecular Analyses Directed Individualized Therapy for Advanced Non-Small Cell Lung Cancer
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Vinorelbine; Docetaxel; Gemcitabine; Carboplatin
Intervention description: Ribonucleotide reductase subunit 1(RRM1)above 16.5 and Excision repair cross-complementing group 1 gene(ERCC1)above 8.7: Treat patients with Docetaxel and Vinorelbine (DV). DV group was treated with vinorelbine (45mg/m2ondays 1 and 15) and docetaxel (60mg/m2ondays 1 and 15) every 28 days.; RRM1 below 16.5 and ERCC1 above 8.7: Treat patients with Gemcitabine and Docetaxel (GD). GD group was treated with gemcitabine (1,250 mg/m2 on days 1 and 8) and docetaxel (40 mg/m2 on days 1 and 8) every 21 days.
RRM1 above 16.5 and ERCC1 below 8.7: Treat patients with Docetaxel and Carboplatin (DC). DC group was treated with docetaxel (75 mg/m2 on day 1) and carboplatin (AUC 5 on day 1) every 21 days.
RRM1 above 16.5 and ERCC1 above 8.7: Treat patients with Docetaxel and Vinorelbine (DV). DV group was treated with vinorelbine (45mg/m2ondays 1 and 15) and docetaxel (60mg/m2ondays 1 and 15) every 28 days.; Ribonucleotide reductase subunit 1(RRM1) below 16.5, and Excision repair cross-complementing group 1 gene(ERCC1) below 8.7: Patients treated with Gemcitabine and Carboplatin (GC). GC group was treated with gemcitabine (1,250 mg/m2 on days 1 and 8) and carboplatin (area under the concentration-time curve [AUC] of 5 on day 1) every 21 days.
RRM1 below 16.5 and ERCC1 above 8.7: Treat patients with Gemcitabine and Docetaxel (GD). GD group was treated with gemcitabine (1,250 mg/m2 on days 1 and 8) and docetaxel (40 mg/m2 on days 1 and 8) every 21 days.; Ribonucleotide reductase subunit 1(RRM1) below 16.5, and Excision repair cross-complementing group 1 gene(ERCC1) below 8.7: Patients treated with Gemcitabine and Carboplatin (GC). GC group was treated with gemcitabine (1,250 mg/m2 on days 1 and 8) and carboplatin (area under the concentration-time curve [AUC] of 5 on day 1) every 21 days.
RRM1 above 16.5 and ERCC1 below 8.7: Treat patients with Docetaxel and Carboplatin (DC). DC group was treated with docetaxel (75 mg/m2 on day 1) and carboplatin (AUC 5 on day 1) every 21 days.
Intervention MeSH terms: Carboplatin; Gemcitabine; Docetaxel; Vinorelbine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: malignant pleural effusion

Summary:

      The standard treatment for non-small cell lung cancer, stage IV or IIIB malignant pleural
      effusion is chemotherapy. The decision to use a regimen is currently determined by toxicity
      or by physician's preference. In this protocol, the treatment regimen will be assigned based
      on the patients' tumor molecular profile. A tumor molecular profile analysis will allow the
      physician to define a specific molecular portrait that shows the genetic basis of the tumor.
      This analysis results in a detailed report that will determine which chemotherapy will be
      assigned to the patient.
    

Eligibility criteria:

        Inclusion Criteria:

          -  histologically confirmed adenocarcinoma, large cell or squamous cell carcinoma NSCLC;
             as well as be willing to undergo a biopsy to enable customization of chemotherapy;
             unresectable/ metastatic (stage IV or IIIB malignant pleural effusion) NSCLC;

          -  male or female, aged > 18 years;

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;

          -  adequate bone marrow, hepatic and renal function assessed within 14 days as evidenced
             by the following:

               1. absolute neutrophil count > 1,500/mm3

               2. platelet count > 100,000/mm3

               3. Hemoglobin > 8gm/dl

               4. no evidence of myelodysplastic syndrome or abnormal bone marrow reserve;

               5. creatinine < 1.5 x upper normal limit(UNL)

               6. total bilirubin must be within normal limits

               7. aspartate aminotransferase(AST)Serum glutamic oxaloacetic transaminase(SGOT)
                  and/or alanine aminotranserase (ALT) serum glutamic pyruvic transaminase(SGPT) <
                  2×5 x UNL in the presence of a normal alkaline phosphatase;

               8. alkaline phosphatases < 4 x UNL in the presence of normal AST and ALT; patients
                  with elevations of both alkaline phosphatase and liver enzymes (AST & ALT) will
                  be excluded.

               9. serum calcium < 1.1 x UNL;

          -  at least one unidimensionally measurable lesion;

          -  signed informed consent;

          -  Women of childbearing potential should have negative pregnancy test prior to
             enrollment to study.

          -  Men with partners in the childbearing age group and women of childbearing potential
             must use effective contraception while on treatment and for 6 months thereafter.

          -  previous surgery (more that 30 days before study entry) is allowed but metastatic
             disease must be demonstrated;

          -  previous radiotherapy is allowed if:

               1. end of radiotherapy 21 days or more prior to study entry;

               2. patient has fully recovered from all toxic effects;

               3. at least one of the measurable target lesions is outside the radiation field.

          -  The patient will be enrolled and re-biopsied at the H Lee Moffitt Cancer Center.
             However since the patients are being treated by FDA approved drugs and with regimens
             for which phase I, phase II or phase III data are available the patients may have
             their chemotherapy administered at the their primary (referring) oncologists office.

          -  Complete initial staging work-up within 4 weeks prior to first infusion of
             chemotherapy.

          -  Patient should have a normal Prothrombin Time (PT) and Activated Prothrombin Time with
             Thromboplastin and kaolin (APTT), to enable him to undergo a biopsy.

          -  Peripheral neuropathy < grade I (according to the NCI-Common Terminology Criteria for
             Adverse Events (CTCAE Version 3.0)

          -  Patients with stable brain metastases will be allowed to enroll. Stable brain
             metastases being defined as no progression of brain metastases 28 days after
             conclusion of definitive treatment as documented by a CT Scan or MRI of the Brain

        Exclusion Criteria:

          -  Pregnant or lactating women

          -  Prior systemic chemotherapy or immunotherapy for advanced NSCLC, patients may have
             received neoadjuvant or adjuvant therapy but more than 6 months prior to study entry;

          -  Prior malignancies, except cured non-melanoma skin cancer, curatively treated in situ
             carcinoma of the cervix or other cancer curatively treated and with non-evidence of
             disease for at least 3 years;

          -  presence of uncontrolled brain or leptomeningeal metastases;

          -  current peripheral neuropathy and hearing deficit of neural origin, CTCAE v3.0 grade 2
             except if due to trauma;

          -  other serious illness or medical condition, including but not limited to:

               1. congestive heart disease; prior myocardial infarction within 6 months;

               2. history of significant neurologic or psychiatric disorders that would inhibit
                  their understanding and giving of informed consent;

               3. infection requiring I.V. antibiotics and tuberculosis under treatment ongoing at
                  study entry;

               4. untreated superior vena cava syndrome;

               5. active peptic ulcer; unstable diabetes mellitus or other contraindication to high
                  dose corticosteroid therapy such as herpes, herpes zoster, cirrhosis;

               6. hypercalcemia requiring therapy at the time of study entry;

               7. preexisting clinically significant ascites and/or clinical significant
                  pericardial effusion;

          -  patients whose lesion(s) are assessable only by radionuclide scan;

          -  patients with a history of severe hypersensitivity reaction to Taxotere or other drugs
             formulated with polysorbate 80 must be excluded

          -  concurrent treatment with other investigational drugs.