Etirinotecan Pegol (NKTR-102) in NSCLC
Condition: Metastatic Non Small Cell Lung Cancer; Recurrent Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Recurrence
Intervention: Etirinotecan pegol (NKTR-102)
Intervention description: Eligible patients will receive etirinotecan pegol at a dose of 145 mg/m2 iv every 3 weeks. One cycle will be defined as 3 weeks. Treatment will be administered on an outpatient basis.
Intervention MeSH terms: Irinotecan; Topoisomerase I Inhibitors; Etirinotecan pegol
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: Male/female subjects 18 years of age and older; metastatic or recurrent NSCLC; who failed 2nd line therapy

Summary:

      This Phase 2 study is designed to characterize the objective response rate (defined as
      complete response (CR) and partial response (PR)) of Etirinotecan pegol administered to
      subjects with metastatic and recurrent NSCLC after failure of 2nd line therapy. Up to 37
      eligible subjects will receive the investigational drug q3 weeks until they are no longer
      benefiting.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed metastatic or recurrent NSCLC. Primary or
             metastatic site may be used for histology.

          -  After failure of 2nd line treatment with up to two prior lines of therapy, one of
             which may be an oral TKI.

          -  Measurable disease (Tumors within a previously irradiated field will be designated as
             "nontarget" lesions unless progression is documented incontrovertibly either
             radiographically or pathologically. For clinicians relying on biopsy documentation of
             recurrence, this must be obtained to confirm persistence at least 90 days following
             completion of radiation therapy).

          -  Eastern Cooperative Oncology Group (ECOG) performance status is 0-1.

          -  Age at the time of study entry is ≥ 18 years.

          -  Adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥
             1500/μL, hemoglobin ≥ 9.0 g/dL, and a platelet count ≥ 100,000/μL obtained within 2
             weeks prior to enrollment.

          -  Adequate hepatic function as defined by a total bilirubin ≤ 1.5 mg/dL, and aspartate
             transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 × the upper limit of normal
             ([ULN]), or ≤ 5 × the ULN in the presence of known liver metastases.

          -  Alkaline phosphatase (AP) ≤ 3 x the ULN or ≤ 5 × the ULN in the presence of known
             liver metastases

          -  Adequate renal function as defined by serum creatinine ≤ 1.5 × the institutional ULN.
             If creatinine is above the ULN, the patient's measured or calculated creatinine
             clearance (CrCl) must be ≥ 50 mL/min.

          -  Resolution of chemotherapy and radiation therapy related toxicities to NCI-CTCAE
             version 4.0 Grade 1 or lower severity, except for diarrhea (which must be Grade 0
             without a supportive antidiarrheal medications) and alopecia (any grade).

          -  Women of childbearing potential and sexually active males must agree to use adequate
             contraception (hormonal or barrier method of birth control; abstinence) prior to
             enrollment and for the duration of study participation. Protections against pregnancy
             must be continued for at least 8 months after the last dose of study drug.

          -  Signed informed consent.

        Exclusion Criteria:

          -  Untreated central nervous system metastases. Patients are eligible if they are
             clinically stable, off all steroids after cranial irradiation (whole brain radiation
             therapy, focal radiation therapy, stereotactic radio surgery) ending at least 2 weeks
             prior to enrollment, or after surgical resection performed at least 2 weeks prior to
             enrollment.

          -  History of another "active" invasive primary cancer requiring ongoing treatment.

          -  Concurrent treatment with other anticancer therapy, including other chemotherapy,
             immunotherapy, hormonal therapy, radiotherapy, chemo-embolization, targeted therapy,
             or an investigational agent.

          -  Patients who have had chemotherapy within 21 days (42 days for nitrosoureas or
             mitomycin C), radiotherapy within 14 days, biological therapy within 14 days, hormonal
             therapy within 7 days, and investigational therapy within 21 days prior to enrollment.

          -  Patients who have had any major surgery within 21 days prior to enrollment.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection requiring parenteral antibiotics, symptomatic congestive heart failure,
             unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
             that would limit compliance with study requirements.

          -  Patients with chronic or acute GI disorders resulting in diarrhea of any severity
             grade; patients who are using chronic anti-diarrheal supportive care (more than 3
             days/week) to control diarrhea in the 28 days prior to enrolment.

          -  Administration of the CYP3A4 inducers or inhibitors, as they may induce or inhibit
             irinotecan or SN38 metabolism within 14 days prior to cycle 1 and throughout study
             treatment. For a list of these agents, see:
             http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteracti
             onsLabeling/ucm093664.htm

          -  Uncontrolled thrombotic or hemorrhagic disorder.

          -  Known human immunodeficiency virus (HIV) positivity.

          -  The patient, if female, is pregnant or lactating.

          -  Previous therapy with a topoisomerase I or II inhibitor.

          -  Known allergy to any of the treatment components.