The 'MADe IT' Clinical Trial: Molecular Analyses Directed Individualized Therapy for Advanced Non-Small Cell Lung Cancer

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.