Clinical Trials /

Safety and Efficacy Study of Nab®-Paclitaxel With CC-486 or Nab®-Paclitaxel With Durvalumab, and Nab®-Paclitaxel Monotherapy as Second/Third-line Treatment for Advanced Non-small Cell Lung Cancer

NCT02250326

Description:

This is a Phase 2, open-label, multicenter study to assess the efficacy and safety of second/third-line treatment with nab-paclitaxel in combination with the epigenetic modifying therapy of CC-486 or immunotherapy of durvalumab, and nab-paclitaxel monotherapy in subjects with advanced non-small cell lung cancer (NSCLC).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Safety and Efficacy Study of <span class="go-doc-concept go-doc-intervention">Nab-Paclitaxel</span> With <span class="go-doc-concept go-doc-intervention">CC-486</span> and <span class="go-doc-concept go-doc-intervention">Nab-Paclitaxel</span> Monotherapy as Second Line Treatment for Advanced Nonsquamous Non-small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span>

Title

  • Brief Title: Safety and Efficacy Study of Nab-Paclitaxel With CC-486 and Nab-Paclitaxel Monotherapy as Second Line Treatment for Advanced Nonsquamous Non-small Cell Lung Cancer
  • Official Title: A PHASE 2, RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY TO ASSESS SAFETY AND EFFICACY OF NAB-PACLITAXEL (ABI-007) WITH EPIGENETIC MODIFYING THERAPY OF CC-486 , AND NAB-PACLITAXEL MONOTHERAPY AS SECOND-LINE TREATMENT IN SUBJECTS WITH ADVANCED NONSQUAMOUS NON-SMALL CELL LUNG CANCER (NSCLC): ABOUND.2L
  • Clinical Trial IDs

    NCT ID: NCT02250326

    ORG ID: ABI-007-NSCL-006

    NCI ID: 2014-001105-41

    Trial Conditions

    Carcinoma, Non-Small-Cell Lung

    Trial Interventions

    Drug Synonyms Arms
    nab-paclitaxel IV Abraxane, ABI-007 Combination arm: nab-paclitaxel and CC-486, Monotherapy arm: nab-paclitaxel IV infusion
    CC-486 Oral AZA, Oral azacitidine Combination arm: nab-paclitaxel and CC-486

    Trial Purpose

    This is a Phase 2, randomized, open-label, multicenter study to assess the efficacy and
    safety of nab-paclitaxel in combination with the epigenetic modifying therapy of CC-486,
    and nab-paclitaxel monotherapy as second-line treatment in subjects with advanced
    nonsquamous NSCLC

    Detailed Description

    This Phase 2 study will test the hypothesis that epigenetic modifying therapy with CC-486
    can improve the anti-tumor activity of nab-paclitaxel in subjects with advanced nonsquamous
    NSCLC who have received one platinum-containing chemotherapy regimen for their advanced
    disease. Approximately 160 male and female subjects with advanced nonsquamous NSCLC will be
    randomized 1:1 into one of the two treatment arms: nab-paclitaxel / CC-486 combination
    therapy or nab-paclitaxel monotherapy prior to receiving first dose of Investigational
    Product.

    Trial Arms

    Name Type Description Interventions
    Combination arm: nab-paclitaxel and CC-486 Experimental Subjects in the combination arm will receive nab-paclitaxel 100 mg^/m2 intravenous (IV) infusion over 30 minutes on Days 8 and 15 and CC-486 200 mg orally daily (QD) on Days 1 to14 of each 21-day treatment cycle nab-paclitaxel IV, CC-486
    Monotherapy arm: nab-paclitaxel IV infusion Experimental Subjects in the monotherapy arm will receive nab-Paclitaxel 100 mg/m^2 IV infusion over 30 minutes on Days 1 and 8 of each 21-day treatment cycle nab-paclitaxel IV

    Eligibility Criteria

    Inclusion Criteria: Subjects must satisfy the following criteria to be randomized in the
    study:

    1. Age 18 years the time of signing the Informed Consent Form (ICF).

    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 advanced nonsquamous NSCLC.

    5. No other current active malignancy requiring anticancer therapy.

    6. Radiographically documented measurable disease (defined by the presence of 1
    radiographically documented measurable lesion).

    7. One prior platinum-containing chemotherapy for the treatment of advanced disease.

    8. Absolute neutrophil count (ANC) 1500 cells/mm3.

    9. Platelets 100,000 cells/mm3.

    10. Hemoglobin (Hgb) 9 g/dL.

    11. Aspartate transaminase (AST/serum glutamic oxaloacetic transaminase [SGOT]) and
    alanine transaminase (ALT/serum glutamic pyruvic transaminase [SGPT]) 2.5 upper
    limit of normal range (ULN) or 5.0 ULN if liver metastases.

    12. Total bilirubin 1.5 ULN (unless there is a known history of Gilberts Syndrome).

    13. Serum creatinine 1.5 x ULN, or calculated creatinine clearance 60 mL/min (if
    renal impairment is suspected 24-hour urine collection for measurement is required).

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

    15. 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 (-hCG) as verified by the study doctor within 72
    hours prior to starting study therapy. She must agree to ongoing pregnancy
    testing during the course of the study, and after end of study therapy. This
    applies even if the subject practices true abstinence* from heterosexual
    contact.

    2. Either commit to true abstinence* from heterosexual contact (which must be
    reviewed on a monthly basis) or agree to use, and be able to comply with,
    effective contraception without interruption, 28 days prior to starting
    investigational product (IP), during the study therapy (including dose
    interruptions), and for 3 months after discontinuation of study therapy.

    Male subjects must:

    a. 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 IP
    discontinuation, even if he has undergone a successful vasectomy.

    16. 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:

    1. Squamous cell NSCLC.

    2. Prior taxane therapy.

    3. Evidence of active brain metastases, including leptomeningeal involvement (prior
    evidence of brain metastasis are permitted only if asymptomatic and clinically
    stable for at least 8 weeks following completion of therapy). MRI of the brain
    (or CT scan w/contrast) is preferred.

    4. Only evidence of disease is non-measurable.

    5. Known EGFR mutation.

    6. Known EML4-ALK mutation.

    7. Preexisting peripheral neuropathy of Grade > 2 (per NCI CTCAE v4.0).

    8. Venous thromboembolism within 1 month prior to Cycle 1 Day 1.

    9. Current congestive heart failure (New York Heart Association Class II-IV).

    10. History of the following within 6 months prior to Cycle 1 Day 1: 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.

    11. Known hepatitis B or C virus (HBV/HCV) infection, known history of human
    immunodeficiency virus (HIV) infection, or receiving immunosuppressive or
    myelosuppressive medications that would in the opinion of the investigator,
    increase the risk of serious neutropenic complications.

    12. 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.

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

    14. Subject has a clinically significant malabsorption syndrome, persistent
    diarrhea, or known sub-acute bowel obstruction > NCI CTCAE Grade 2, despite
    medical management.

    15. Treatment with any investigational product within 28 days prior to signing the
    ICF.

    16. History of or suspected allergy to nab-paclitaxel, azacitidine, human albumin or
    mannitol.

    17. Currently enrolled in any other clinical protocol or investigational trial that
    involves administration of experimental therapy and/or therapeutic devices.

    18. 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.

    19. Any other malignancy within 5 years prior to randomization, or advanced
    malignant hepatic tumors, with the exception of adequately treated 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 Classification of Malignant Tumours (TNM) stage of T1a
    or T1b). (All treatment of which should have been completed 6 months prior to
    signing ICF).

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

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

    22. Pregnant or breastfeeding females.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression free survival

    Secondary Outcome Measures

    Adverse Events

    Disease Control Rate

    Overall Survival

    Overall Response Rate

    Discontinuation rate

    Median dose intensity

    Incidence of dose reduction

    Trial Keywords

    Cancer of the Lung

    Lung neoplasm

    Non-small cell lung cancer (NSCLC)

    Nonsquamous

    Tumor

    Locally advanced NSCLC

    Metastatic NSCLC

    Advanced lung cancer

    Metastatic lung cancer

    Non-squamous NSCLC

    Lung cancer

    Abraxane

    ABI-007

    Nab-paclitaxel,

    Albumin-bound paclitaxel

    Taxanes

    CC-486

    Oral azacitidine

    Azacitidine

    Second line treatment of lung cancer

    Second line treatment

    Celgene

    Abound.2L