Phase II Safety and Tolerability Trial With Nab-Paclitaxel Plus Carboplatin Followed by Nab-Paclitaxel for First Line Treatment of NSCLC Subjects With ECOG PS 2
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: nab-Paclitaxel; Carboplatin
Intervention MeSH terms: Paclitaxel; Carboplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Phase II, LOCALLY ADVANCED OR METASTATIC NON SMALL; CELL LUNG CANCER (NSCLC) AND AN; EASTERN COOPERATIVE ONCOLOGY GROUP; PERFORMANCE STATUS OF 2; (ABOUND.PS2); LOCALLY ADVANCED OR METASTATIC NON SMALL; CELL LUNG CANCER (NSCLC) SUBJECTS THAT AE NOT CANDIDATES FOR RADIATION OR CURATIVE SURGERY

Summary:

      4 cycles of induction treatment with nab-paclitaxel and carboplatin followed by
      nab-paclitaxel monotherapy for those subjects who are progression free at the end of 4
      cycles.
    

Eligibility criteria:

        Inclusion Criteria:

          -  General and Demographics

               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 Non-Small Cell Lung
                  Cancer.

               5. Radiographically documented measurable disease at study entry per response
                  evaluation criteria in solid tumours ( RECIST) v1.1.

               6. No prior anti-cancer therapy for the treatment of metastatic disease at the time
                  of signing the ICF. Adjuvant treatment is permitted providing cytotoxic
                  chemotherapy was completed 12 months prior to signing the ICF and without disease
                  recurrence.

               7. Absolute neutrophil count (ANC) ≥ 1500 cells/mm3.

               8. Platelets ≥ 100,000 cells/mm3.

               9. Hemoglobin (Hgb) ≥ 9 g/dL.

              10. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]),
                  alanine transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 ×
                  upper limit of normal range (ULN) or ≤ 5.0 × ULN if liver metastases.

              11. Total bilirubin ≤ 1.5 × ULN except in cases of Gilbert's disease and liver
                  metastases.

              12. Serum creatinine ≤ 1.5 x ULN, or calculated creatinine clearance ≥ 40 mL/min (if
                  renal impairment is suspected 24-hour urine collection for measurement is
                  required).

              13. Eastern Cooperative Oncology Group Performance Status 2.

              14. 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 (ie, has had menses
                  at any time during the preceding 24 consecutive months)] must:

                    1. Have a negative pregnancy test Beta Human Chorionic Gonaditrophin(ß-hCG) as
                       verified by the study doctor within 72 hours prior to starting study
                       therapy.

                    2. You must commit to complete abstinence from heterosexual contact, or agree
                       to use medical doctor-approved contraception throughout the study without
                       interruption; while receiving study medication or for a longer period if
                       required by local regulations.

                       Male subjects must:

                    3. 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 at least 6
                       months following study drug discontinuation, even if he has undergone a
                       successful vasectomy.

        Exclusion Criteria:

          -  The presence of any of the following will exclude a subject from enrollment:

               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 at least 21days prior to signing ICF). MRI of the brain (or CT scan
                  w/contrast) is preferred for diagnosis.

               2. History of leptomeningeal disease.

               3. Only evidence of disease is non-measurable.

               4. Pre-existing peripheral neuropathy of Grade 2, 3, or 4 (per Criteria for Adverse
                  Events (CTCAE) v4.0).

               5. 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.

               6. Venous thromboembolism within 1 month prior to signing ICF.

               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
                  investigational product: 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 ECG abnormality,
                  cerebrovascular accident, transient ischemic attack, or seizure disorder.

               9. Subject has a known infection with hepatitis B or C, or history of human
                  immunodeficiency virus (HIV) infection, or subject receiving immunosuppressive or
                  myelosuppressive medications that would in the opinion of the investigator,
                  increase the risk of serious neutropenic complications.

              10. Subject 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
                  ICF.

              13. History of or suspected allergy to nab-paclitaxel, carboplatin and human albumin
                  or any other platinum-based therapy.

              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. Subject has any other malignancy within 5 years prior to signing the ICF.
                  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, node
                  and metastasis (TNM) stage of T1a or T1b). All treatment should have been
                  completed 6 months prior to signing ICF.

              17. Any condition including the presence of laboratory abnormalities, which places
                  the subject 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. This includes subjects with known psychiatric disorders.

              19. Pregnant or breast-feeding females.

              20. Subjects with an ECOG PS other than 2