Phase 2 Etirinotecan Pegol in Refractory Brain Metastases & Advanced Lung Cancer / Metastatic Breast Cancer
Condition: Stage IV Non-small Cell Lung Cancer (NSCLC); Recurrent Non-small Cell Lung Cancer (NSCLC); Extensive-stage Small Cell Lung Cancer (SCLC); Recurrent Small Cell Lung Cancer (SCLC); Tumors Metastatic to Brain; Metastatic Breast Cancer (mBC)
MeSH terms: Breast Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Brain Neoplasms; Recurrence
Intervention: Pegylated Irinotecan
Intervention description: Administered intravenously (IV) at 145 mg/m² as monotherapy once every 21 days (1 cycle)
Intervention MeSH terms: Irinotecan; Etirinotecan pegol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase 2 trial evaluates how well pegylated irinotecan (NKTR-102) works in treating
      patients with non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), or breast
      cancer (mBC) that has spread to the brain and does not respond to treatment. Pegylated
      irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  At least 18 years of age.

          -  Life expectancy of 3 months or longer.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

        Advanced or refractory cancer, consisting of

          -  Metastatic breast cancer (mBC) for which single-agent cytotoxic chemotherapy is
             indicated. OR

          -  Histologically-proven metastatic lung cancer:

               -  Non-small cell lung cancer (NSCLC) as Stage IV disease or recurrent metastatic
                  disease [per lung cancer tumor, node and metastasis (TNM) classification system,
                  7th ed] (Cohort A) OR

               -  Small cell lung cancer (SCLC) as extensive stage or recurrent metastatic disease
                  (cohort B), including tumors with mixed small cell and non-small cell elements.

        Prior chemotherapy (at least one of the following):

          -  At least one line of prior systemic chemotherapy

          -  At least one line of prior targeted treatment for metastatic disease Adjuvant systemic
             chemotherapy within prior 6 months Prior treatment for metastatic breast cancer (mBC)
             must have included taxane-based regimen

        Prior chemotherapy, including other investigational therapy, has been completed prior to
        initiation of study treatment, according to the following:

          -  ≥ 2 weeks if immediately preceding treatment was chemotherapy/targeted therapy
             administered on a daily or weekly schedule

          -  ≥ 3 weeks if immediately preceding treatment was chemotherapy/targeted therapy
             administered every 2 weeks

          -  ≥ 4 weeks if immediately preceding treatment was chemotherapy/targeted therapy
             administered every 3 weeks Previously received at least one CNS directed treatment
             (such as surgery or radiation) OR not be eligible for CNS stereotactic radiosurgery
             Measurable CNS disease, either previously untreated (not counting systemic therapy),
             or progressed following previous radiation treatment. Lesions that have progressed
             after prior radiosurgery should not be selected as measurable disease if they are
             suspected of being radionecrosis.

        The following measurement criteria are required, as visualized by contrast-enhanced MRI
        with slice thickness of ≤ 1.5 mm, unless absence of contrast or thicker slices is
        specifically authorized by Protocol Director. Measurements do not include tumor edema.

          -  At least one CNS tumor measuring ≥ 10 mm in longest diameter, OR

          -  At least one CNS tumor measuring 5-9 mm in longest diameter, plus one or two
             additional CNS tumors measuring ≥ 3 mm in longest diameter, for which the sum of the
             longest diameters is ≥ 10 mm. Additional tumors are not exclusionary.

        Adequate organ function as evidenced by:

          -  Absolute neutrophil count (ANC) ≥ 1.5 x 10e9/L without G-CSF (filgrastim,
             pegfilgrastim, or equivalent) support within 7 days

          -  Hemoglobin (Hgb) ≥ 9.0 g/dL (90 g/L) without blood transfusion within 7 days

          -  Platelet count ≥ 100 x 10e9/L without platelet transfusion within 7 days

          -  Bilirubin ≤ 1.5 X upper limit of normal (ULN), except for patients with documented
             history of Gilbert's disease who may have DIRECT bilirubin ≤ 1.5 X ULN

          -  Alanine aminotransferase (ALT) ≤ 2.5 X ULN, except ≤ 5 X ULN for patients with liver
             metastases

          -  Aspartate aminotransferase (AST) ≤ 2.5 X ULN, except ≤ 5 X ULN for patients with liver
             metastases

          -  Serum creatinine ≤ 1.5 X ULN; or calculated creatinine clearance ≥ 50 mL/min (using
             Cockcroft-Gault formula), or measured creatinine clearance ≥ 50 mL/min.

        Exclusion Criteria:

          -  Previous treatment with a camptothecin derivative (eg, irinotecan, topotecan, and
             investigational agents including but not limited to exatecan, rubitecan, gimatecan,
             karenitecin, SN38 investigational agents, EZN 2208, SN 2310, and AR 67) is not allowed

          -  Patients may not have a known history of leptomeningeal disease, as diagnosed by
             positive CSF cytology, unless prospective permission for enrollment is granted from
             the sponsor and the PI

          -  Patients may not have had major surgery or radiotherapy (therapeutic and/or
             palliative) within 14 days prior to initiation of study treatment, including
             CNS-directed radiation therapy. Minor procedures, such as tumor biopsy, thoracentesis,
             or intravenous catheter placement are allowed with no waiting period

          -  Patients may not have the following co morbid disease or concurrent illness:

               -  Chronic or acute gastrointestinal (GI) disorders resulting in diarrhea of any
                  severity grade; patients may not use chronic anti-diarrheal supportive care (more
                  than 3 days/week) to control diarrhea in the 28 days prior to first dose of
                  investigational drug. (exception: anti-diarrheal medications used to control
                  symptoms from a medication that will be discontinued prior to study are allowed
                  with a 7 day washout before study therapy, for example loperamide for
                  erlotinib-associated diarrhea)

               -  Known cirrhosis, defined as Child Pugh class A or higher liver disease

               -  Other active malignancy, except for non melanoma skin cancer and carcinoma in
                  situ (of the cervix or bladder)

               -  Any other severe/uncontrolled inter current illness or significant co morbid
                  conditions that in the opinion of the investigator would impair study
                  participation or cooperation

          -  Patients may not have a known allergy or hypersensitivity to any of the components of
             the investigational therapy, including polyethylene glycol (PEG) or topoisomerase
             inhibitors

          -  Patients may not be receiving the following medications at the time of first dose of
             investigational drug:

               -  Pharmacotherapy for known hepatitis B or C, tuberculosis, or human
                  immunodeficiency virus (HIV)

               -  Any of the following enzyme inducing anti epileptic medications (EIAEDs):
                  phenytoin, carbamazepine, oxcarbazepine, phenobarbital

               -  Other chemotherapy, hormonal therapy, immunotherapy, other investigational
                  agents, or biologic agents for the treatment of cancer except for bisphosphonates
                  or denosumab

          -  Pregnant or nursing patients will be excluded from the study