Safety and Efficacy Study of Abraxane in Combination With Carboplatin to Treat Advanced NSCL Cancer in the Elderly

This is a Phase IV, randomized, open-label, multicenter study of continuous weekly versus
weekly times three with one-week break nab-paclitaxel in combination with carboplatin as
first-line treatment in elderly subjects (≥ 70 years old) with advanced non small cell lung
cancer who have not received prior chemotherapy for their advanced disease and are not
candidates for curative surgery or radiation therapy. The primary study endpoint is the
percentage of subjects with either peripheral neuropathy or myelosuppression adverse events.
Patients will continue treatment until they develop progressive disease, unacceptable
side-effects or wish to withdraw from the study, according to local standard of care.
Patients will have radiographic evaluations every 6 weeks while on treatment.

Inclusion Criteria: -

- Inclusion Criteria: -

1. Age ≥ 70 years at the time of signing the Informed Consent Form.

2. Understand and voluntarily provide written informed consent prior to the conduct
of any study related assessments/procedures.

3. Able to adhere to the study visit schedule and other protocol requirements.

4. Histologically or cytologically confirmed locally advanced or metastatic non
small cell lung cancer who are not candidates for curative surgery or radiation
therapy.

5. No other current active malignancy requiring anticancer therapy.

6. Radiographically documented measurable disease per RECIST v 1.1

7. No prior chemotherapy for the treatment of metastatic disease. Adjuvant
chemotherapy is permitted providing that cytotoxic chemotherapy was completed 12
months prior to signing the informed consent form (ICF) and without disease
recurrence. Participans with previously known epidermal growth factor receptor
mutation or anaplastic lymphoma kinase gene translocation must have failed or had
intolerance to one treatment with epidermal growth factor receptor tyrosine
kinase inhibitor or anaplastic lymphoma kinase inhibitor therapy, respectively.

8. Absolute neutrophil count ≥ 1500 cells/cubic millimetre.

9. Platelets ≥ 100,000 cells/cubic millimetre.

10. Hemoglobin ≥ 9 grams/decilitre.

11. Aspartate transaminase/serum glutamic oxaloacetic transaminase/ alanine
transaminase/serum glutamic pyruvic transaminase ≤ 2.5 × upper limit of normal
range or ≤ 5.0 × upper limit of normal range if liver metastases.

12. Total bilirubin ≤ 1.5 millilitre/decilitre (unless there is a known history of
Gilberts Syndrome).

13. Creatinine clearance > 40 millilitre/minute calculated using Cockcroft-Gault
equation (if renal impairment is suspected 24 hour urine collection for
measurement is required).

14. Eastern Cooperative Oncology Group performance status 0 or 1.

15. Females who (1) have undergone hysterectomy (the surgical removal of the uterus)
or bilateral oophorectomy (the surgical removal of both ovaries) or (2) have been
naturally postmenopausal for at least 24 consecutive months (ie, has not had
menses at any time during the preceding 24 consecutive months).

16. Male subjects must: Practice true abstinence or agree to use a condom during
sexual contact with a pregnant female or a female of childbearing potential while
participating in the study, during dose interruptions and for 6 months following
study drug discontinuation, even if he has undergone a successful vasectomy.

Exclusion Criteria:

- 1. Evidence of active brain metastases, including leptomeningeal involvement (prior
evidence of brain metastasis are permitted only if treated and stable and off therapy
for ≥ 4 weeks prior to signing Informed consent form. Magnetic Resonance Imaging of
the brain (or Computed Tomography scan w/contrast) is preferred for diagnosis.

2. History of leptomeningeal disease. 3. Only evidence of disease is non measurable.
4. Preexisting peripheral neuropathy of Grade 2, 3, or 4 (per Common Terminology
Criteria for Adverse Events v4.0).

5. Participant has received radiotherapy ≤ 4 weeks or limited field radiation for
palliation ≤ 2 weeks prior to starting investigational product, and/or from whom ≥ 30%
of the bone marrow was irradiated. Prior radiation therapy to a target lesion is
permitted only if there has been clear progression of the lesion since radiation was
completed.

6. Venous thromboembolism within 1 month prior to signing informed consent form.

7. Current congestive heart failure (New York Heart Association Class II-IV). 8.
History of the following within 6 months prior to first administration of a study
drug: a myocardial infarction, severe/unstable angina pectoris,coronary/peripheral
artery bypass graft, New York Heart Association Class III-IV heart failure,
uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically
significant Electrocardiogram abnormality, cerebrovascular accident, transient
ischemic attack, or seizure disorder.

9. Participant has a known infection with hepatitis B or C, or history of human
immunodeficiency virus infection, or participant is receiving immunosuppressive or
myelosuppressive medications that would in the opinion of the investigator, increase
the risk of serious neutropenic complications.

10. Participant has an active, uncontrolled bacterial, viral, or fungal infection(s)
requiring systemic therapy, defined as ongoing signs/symptoms related to the infection
without improvement despite appropriate antibiotics, antiviral therapy, and/or other
treatment.

11.History of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary
fibrosis, or pulmonary hypersensitivity pneumonitis.

12. Treatment with any investigational product within 28 days prior to signing the
informed consent form.

13. History of allergy or hypersensitivity to nab-paclitaxel or carboplatin. 14.
Currently enrolled in any other clinical protocol or investigational trial that
involves administration of experimental therapy and/or therapeutic devices. 15. Any
other clinically significant medical condition, psychiatric illness, and/or organ
dysfunction that will interfere with the administration of the therapy according to
this protocol or which, in the views of investigator, preclude combination
chemotherapy.

16. Participant has any other malignancy within 5 years prior to randomization.
Exceptions include the following: squamous cell carcinoma of the skin, in-situ
carcinoma of the cervix, uteri, non-melanomatous skin cancer, carcinoma in situ of the
breast, or incidental histological finding of prostate cancer Tumor, Lymph Node,
Metastatic (TNM stage of T1a or T1b). All treatment of which should have been
completed 6 months prior to signing Informed consent form.

17. Any condition including the presence of laboratory abnormalities, which places the
participant at unacceptable risk if he/she were to participate in the study.

18. Any medical condition that confounds the ability to interpret data from the study.

19. Females who (1) have not undergone hysterectomy (the surgical removal of the
uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or (2) have
not been naturally postmenopausal for at least 24 consecutive months (ie, has had
menses at any time during the preceding 24 consecutive months).