The primary objective of this trial is to compare the treatment failure-free survival rate in
high-risk elderly patients, identified by geriatric assessment, treated with either a
platinum-based doublet chemotherapy with carboplatin/nab-paclitaxel or single agent
nab-paclitaxel in advanced non-small cell lung cancer. Treatment failure-free survival is the
most appropriate primary outcome as it captures excessive toxicity due to chemotherapy in
addition to death and disease progression.
The secondary objectives are to evaluate grade 3-5 toxicities, overall response rate,
progression free survival, symptom assessment, and overall survival between the two
randomization arms.
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.
