Single Agent Versus Combination Chemotherapy to Treat High-risk Elderly With Non-small Cell Lung Cancer
Condition: Carcinoma, Non-small Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Carboplatin; Nab-paclitaxel
Intervention MeSH terms: Paclitaxel; Carboplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 71 Years
Healthy volunteers: No

Summary:

      This study will enroll elderly patients with advanced non-small cell lung cancer who are at
      high risk of developing chemotherapy toxicity (side effects). Patients will receive treatment
      with either a platinum-based doublet chemotherapy with carboplatin/nab-paclitaxel or single
      agent nab-paclitaxel of chemotherapy. Response to treatment and treatment toxicity will be
      compared in the two treatment groups to determine the best treatment strategy for this group
      of patients.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient able and willing to comply with study procedures as per protocol, including
             the geriatric assessment at the time of study enrollment.

          2. Patient able to understand and willing to sign and date the written voluntary informed
             consent form (ICF) at screening visit prior to any protocol-specific procedures.

          3. Patients must have histological or cytological confirmed primary non-small cell lung
             cancer (adenocarcinoma, large cell carcinoma, squamous, or unspecified). Disease must
             be stage IV Non-Small Cell Lung Cancer (NSCLC). Disease may be either newly diagnosed
             or recurrent after previous surgery and/or irradiation. Primary or metastatic site for
             biopsy is allowed

          4. Patients may have measurable or non-measurable disease documented by CT or MRI. The CT
             from a combined PET/CT may be used to document only non-measurable disease. Measurable
             disease must be assessed within 30 days prior to registration per response evaluation
             criteria in solid tumors (RECIST) v1.1. Pleural effusions, ascites and laboratory
             parameters are not acceptable as the only evidence of disease. Non- measurable disease
             must be assessed within 30 days prior to registration. All disease must be assessed
             and documented on the Baseline Tumor Assessment Form.

          5. Prior chemotherapy for curative intent is permitted providing the cytotoxic
             chemotherapy was completed ≥12 months prior to enrollment. Patients must have a CT or
             MRI scan of the brain to evaluate for CNS disease within 30 days prior to
             registration. Patient must not have brain metastases unless: (1) metastases have been
             treated and have remained controlled for at least two weeks following treatment, AND
             (2) patient has no residual neurological dysfunction off corticosteroids for at least
             1 day. Any radiation therapy completed prior to chemotherapy, except gamma-knife
             radiosurgery, 1 week prior to chemotherapy.

          6. Age >70 years of age at time of signing of the informed consent form.

          7. Life expectancy of greater than 12 weeks.

          8. ECOG performance status 0-2 (See Appendix A)

          9. Patients must have a comprehensive geriatric assessment and chemotherapy toxicity
             assessment score between 7-17 (See Appendix B, D)

         10. Patients must have normal organ and marrow function as defined below:

               -  Leukocytes >3,000/mcL

               -  ANC > 1,500 cells/mm3Hemoglobin > 9.0g/dL

               -  Platelets >100,000 cells/mm3

               -  Total bilirubin < 1.5 mg/dL (unless there is a known history of Gilberts
                  Syndrome).

               -  AST(SGOT)/ALT(SGPT) ≤2.5 X institutional upper limit of normal

               -  Alkaline phosphatase < 2.5 X upper limit of normal in the absence of liver or
                  bone metastasis, or ≤ 5.0 × upper limit of normal range if bone or liver
                  metastases

               -  Creatinine clearance >25 mL/min or creatinine <1.5 mg/dL

         11. HIV-positive patients on combination antiretroviral therapy are eligible if they have
             been on ARVs for ≥6 months and undetectable viral loads.

         12. Patients must not have documented evidence of acute hepatitis or have an active or
             uncontrolled infection.

         13. No other priormalignancy is allowed except for the following: adequately treated basal
             cell or squamous cell skin cancer, in-situ cervical cancer, adequately treated Stage I
             or II cancer from which the patient is currently in complete remission, or any other
             cancer from which the patient has been disease-free for 5 years.

         14. Ability to understand and the willingness to sign a written informed consent document
             in English or a Spanish consent "short form". If language other than English or
             Spanish, then interpreter will be used to sign English consent form.

         15. Patients must have < Grade 2 pre-existing peripheral neuropathy (per CTCAE)

        Exclusion Criteria

          1. Patients who have had palliative chemotherapy prior to entering the study <12 months
             from enrollment or those who have not recovered from adverse events due to agents
             administered more than 4 weeks earlier.

          2. Patients may not be receiving any other investigational agents or have received
             immunotherapy.

          3. Known EGFR or ALK mutated disease (molecular testing not required prior to study
             entry)

          4. History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to carboplatin, or nab-paclitaxel.

          5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          6. Preexisting peripheral neuropathy of Grade 2, 3, or 4 (per Common Terminology Criteria
             for Adverse Events v4.0)

          7. Evidence of active brain metastases, including leptomeningeal involvement (prior
             evidence of brain metastasis are permitted only if treated and stable and off therapy
             for ≥ 2 weeks prior to signing Informed consent form. Magnetic Resonance Imaging of
             the brain (or Computed Tomography scan w/contrast) is preferred for diagnosis.