Details

Details

Title A Phase 3, multicenter, open-label, randomized study of nab®-paclitaxel plus gemcitabine versus gemcitabine alone as adjuvant therapy in subjects with surgically resected pancreatic adenocarcinoma

IRB CLGN1214

CC 14-468

Hospital Fairview, Hillcrest, Independence, Main Campus

Phase Phase 3

Disease Pancreas

Drug Gemcitabine , Nab-Paclitaxel

Description

Description

Primary Objective
  • To compare DFS between subjects randomized to nabpaclitaxel in combination with gemcitabine and subjects randomized to gemcitabine alone.
Secondary Objectives
    Assess OS between subjects randomized to nab-paclitaxel in combination with gemcitabine and subjects randomized to gemcitabine alone
  • Evaluate safety and tolerability
Exploratory Objectives
  • Assess tumor molecular heterogeneity and associate identified tumor molecular subtypes with clinical outcome
  • Investigate whether circulating nucleic acids are associated with disease recurrence
  • Evaluate the effect of nab-paclitaxel in combination with gemcitabine and gemcitabine alone on subject quality of life (QoL)
Inclusion Criteria

Inclusion Criteria

  1. Histologically confirmed resected ductal pancreatic adenocarcinoma with macroscopic complete resection (R0 and R1). Subjects with neuroendocrine (and mixed type) tumors are excluded.
  2. Pancreatic cancer staging: T 1-3, N0-1, M0.
  3. Subject should be able to start treatment no later than 12 weeks postsurgery.
  4. Male or non-pregnant, non-lactating females who are ≥18 years of age at the time of signing the informed consent form (ICF).
  5. ECOG performance status of 0 or 1
  6. Acceptable hematology parameters:
    • Absolute neutrophil count ≥1500 cell/mm3
    • Platelet count ≥100,000/mm3
    • Hemoglobin (Hgb) ≥9 g/dL
  7. Acceptable blood chemistry levels:
    • AST/ SGOT and ALT/ SGPT ≤2.5 x upper limit of normal range (ULN)
    • Total bilirubin ≤ ULN (subjects with Gilbert's syndrome can have bilirubin of up to 1.5 x ULN)
    • Alkaline phosphatase ≤ 2.5 x ULN
    • Serum creatinine within upper limits of normal or calculated clearance ≥50 mL/min/1.73 m2. If using creatinine clearance, actual body weight should be used for calculating creatinine clearance (eg, using the Cockroft-Gault formula). For subjects with a Body Mass Index (BMI) >30 kg/m2, lean body weight should be used instead
  8. CA19-9 <100 U/mL assessed within 14 days of randomization
  9. Acceptable coagulation studies (eg. PT or INR, and PTT within normal limits, +/-15%)
  10. Females of child-bearing potential (defined as a sexually mature woman who (1) has not undergone hysterectomy [the surgical removal of the uterus] or bilateral oophorectomy [the surgical removal of both ovaries] or (2) has not been naturally postmenopausal for at least 24 consecutive months [ie, has had menses at any time during the preceding 24 consecutive months]) must:
    • Agree to the use of two physician-approved contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study IP; and for 3 months following the last dose of IP; and
    • Has negative serum pregnancy test (β -hCG) result at screening
  11. 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 IP discontinuation, even if he has undergone a successful vasectomy.
  12. Understand and voluntarily sign an ICF prior to any study related assessments or procedures being conducted.
  13. Be able to adhere to the study visit schedule and other protocol requirements.
Exclusion Criteria

Exclusion Criteria

  1. Prior neo-adjuvant treatment, radiation therapy, or systemic therapy for pancreatic adenocarcinoma
  2. Presence of or history of metastatic or locally recurrent pancreatic adenocarcinoma
  3. Any other malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, or nonmelanomatous skin cancer (all treatment of which should have been completed 6 months prior to randomization)
  4. 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
  5. Known history of human immunodeficiency virus (HIV) infection, or known history of active hepatitis B or C and are currently serologically positive with evidence of prior or signs of active chronic hepatitis
  6. History of allergy or hypersensitivity to nab-paclitaxel or gemcitabine or any of their excipients
  7. Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the subject's safety or the study data integrity. These include, but are not limited to:
    • History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa)
    • History of interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies
    • 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 ECG abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder
    • Peripheral neuropathy > grade 2
    • Concomitant use of immunosuppressive or myelosuppressive medications that would in the opinion of the investigator, increase the risk of serious neutropenic complications
  8. Enrollment in any other clinical protocol or investigational study with an interventional agent or assessments that may interfere with study procedures
  9. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
  10. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
  11. Any condition that confounds the ability to interpret data from the study
  12. Unwillingness or inability to comply with study procedures