Safety and Efficacy Study of Abraxane as Maintenance Treatment After Abraxane Plus Carboplatin in 1st Line Stage IIIB / IV Squamous Cell Non-small Cell Lung Cancer

A Phase III, Randomized, Open-Label, Multi-Center, Safety and Efficacy Study to Evaluate Nab-Paclitaxel (Abraxane®) as Maintenance Treatment After Induction With Nab-Paclitaxel Plus Carboplatin in Subjects With Squamous Cell Non-Small Cell Lung Cancer (NSCLC)

Maintenance treatment of advanced stage squamous cell NSCLC.

Phase III, randomized, open-label, multi-center study of nab-paclitaxel with best supportive care (BSC) or BSC alone as maintenance treatment after response or stable disease (SD) with nab-paclitaxel plus carboplatin as induction in subjects with stage IIIB/IV squamous cell NSCLC.

Subjects who discontinued treatment from the maintenance part for any reason other than withdrawal of consent, lost to follow-up, or death, were entered into a Follow-up period that had a visit 28 days after progression or discontinuation.

Those who entered Follow-up without progression continued with follow-up scans according to standard of care (SOC) until documentation of progression of disease. Additionally, subjects were followed for OS by phone approximately every 90 days for a minimum of 18 months, for up to approximately 5 years after the last subject was randomized.

The sponsor used 15 Sep 2017 as the database cut-off date.

Inclusion Criteria:

1. Age ≥ 18 years of age at the time of signing the Informed Consent Form.

2. Understand and voluntarily provide written consent to the Informed Consent Form prior to conducting any study related assessments/procedures.

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

   Disease Specific

4. Histologically or cytologically confirmed Stage IIIB or IV squamous cell Non Small Cell Lung Cancer at study entry.

5. No other current active malignancy requiring anticancer therapy.

6. Radiographically documented measurable disease at study entry (as defined by the Response Evaluation Criteria In Solid Tumors [RECIST] v1.1 criteria).

7. No prior chemotherapy for the treatment of metastatic disease at study entry. Adjuvant chemotherapy is permitted providing cytotoxic chemotherapy was completed 12 months prior to starting the study and without disease recurrence.

8. Absolute neutrophil count ≥ 1500 cells/mm^3.

9. Platelets ≥ 100,000 cells/mm^3.

10. Hemoglobin ≥ 9 g/dL.

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 × upper limit of normal range except in cases of Gilbert's disease and liver metastases.

13. Creatinine ≤ 1.5 mg/dL.

14. Expected survival of > 12 weeks for the Induction part of the study.

15. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

16. For Maintenance part of the study, subjects must have received at least one dose of nab-paclitaxel in each of the 4 cycles during Induction

    Pregnancy

17. Females of childbearing potential [defined as a sexually mature woman 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 (i.e., has had menses at any time during the preceding 24 consecutive months)] must:

    1. agree to take a pregnancy test prior to starting study medication and throughout the study participation.
    2. commit to complete abstinence from heterosexual contact, or agree to use medical doctor-approved contraception throughout the study without interruption, and while receiving study medication or for a longer period if required by local regulations.

18. Male subjects must:

    c. agree to complete abstinence from heterosexual contact or use a condom during sexual contact with a female of child bearing potential while receiving study medication and within 6 months after last dose of study medication, even if he has undergone a successful vasectomy.

19. Females must abstain from breastfeeding during study participation and 3 months after IP discontinuation.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment into the Induction and Maintenance parts of the study (except if specified at study entry only):

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 first dose of study drug).
2. Only evidence of disease is non-measurable at study entry.
3. Preexisting peripheral neuropathy of Grade 2, 3, or 4 (per Common Terminology Criteria for Adverse Events v4.0).
4. Venous thromboembolism within 6 months prior to signing Informed Consent Form.
5. Current congestive heart failure (New York Heart Association class II-IV).
6. 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 (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram (ECG) abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder.
7. Treatment with any investigational product within 28 days prior to signing Informed Consent Form.
8. History of allergy or hypersensitivity to nab-paclitaxel or carboplatin.
9. Currently enrolled in any other clinical protocol or investigational trial that involved administration of experimental therapy and/or therapeutic devices.
10. Any other clinically significant medical condition and/or organ dysfunction that will interfere with the administration of the therapy according to this protocol.
11. Subject 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 (TNM stage of T1a or T1b) - all treatments that should have been completed 6 months prior to signing informed consent form (ICF).
12. Subject has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting investigational product (IP), 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.
13. Pregnant and nursing females.