Etirinotecan Pegol in Treating Patients with Refractory Brain Metastasis from Non-small Cell Lung Cancer or Small Cell Lung Cancer or Metastatic Breast Cancer

Inclusion Criteria

• Patients must have histologically proven metastatic non-small cell lung cancer (stage IV disease or recurrent metastatic disease, according to the 7th edition of the lung cancer tumor, nodes, metastasis [TNM] classification system) (for cohort A), or histologically proven metastatic small cell lung cancer (extensive stage or recurrent metastatic disease) for cohort B; (patients with tumors having mixed small cell and non-small cell elements may be enrolled on cohort B), or females with histologically or cytologically confirmed carcinoma of the breast (either the primary or metastatic lesions) for whom single-agent cytotoxic chemotherapy is indicated
• Patients must have previously received at least one line of prior systemic chemotherapy or targeted treatment for metastatic disease OR have received prior adjuvant systemic chemotherapy within prior 6 months; patients with MBC, must have received at least a taxane based regimens; patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma receptor tyrosine kinase (ALK) mutations should have failed prior standard tyrosine kinase inhibitor (TKI) therapy; patients must have completed previous treatment (including other investigational therapy) in greater than or equal to the following times prior to initiation of study treatment: * Chemotherapy/targeted therapy administered in a daily or weekly schedule must be completed >= 2 weeks prior to study treatment * Chemotherapy/targeted therapy administered in a 2-weekly schedule must be completed >= 3 weeks prior to study treatment * Chemotherapy/targeted therapy administered in a 3-weekly or greater schedule must be completed >= 4 weeks prior to study treatment
• Patients must have previously received at least one CNS directed treatment (such as surgery or radiation) OR not be eligible for CNS stereotactic radiosurgery
• Patients must have 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 (not counting tumor edema, as visualized by contrast enhanced magnetic resonance imaging [MRI] with slice thickness of 1.5 mm or smaller, unless prospective permission is obtained from the principal investigator [PI] allowing absence of contrast or thicker slices): * At least one CNS tumor measuring 10 mm or greater 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 or greater in longest diameter, for which the sum of the longest diameters is equal to or greater than 10 mm; patient may have additional tumors as well
• Patients must have a life expectancy of 3 months or longer
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Women of childbearing potential (less than 12 consecutive months since last regular menses, or surgically sterile) must have a negative serum beta-human chorionic gonadotropin (hCG) pregnancy test and must agree to use hormonal, intrauterine device (IUD), or barrier birth control with spermicide to avoid pregnancy during the study; agreement to participate in this study via the informed consent will indicate subjects commitment to subject avoid pregnancy in self or a partner of childbearing potential for up to 6 months after the last dose of study therapy
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L without filgrastim (GCSF) support within 7 days
• Hemoglobin (Hgb) >= 9.0 g/dL (90 g/L) without blood transfusion within 7 days
• Platelet count >= 100 x 10^9/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 upper limit of normal (ULN)
• Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =< 2.5 x ULN (for patients with liver metastases, =< 5 x ULN)
• Serum creatinine =< 1.5 x ULN; or calculated creatinine clearance >= 50 mL/min (using Cockcroft Gault formula); or measured creatinine clearance >= 50 mL/min
• Patients must be willing and able to comply with the protocol and provide written informed consent prior to study specific screening procedures

Exclusion Criteria

• Previous treatment with a camptothecin derivative (eg., irinotecan, topotecan, and investigational agents including but not limited to exatecan, rubitecan, gimatecan, karenitecan, 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 cerebrospinal fluid (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 malignancy undergoing active treatment * 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
• Significant unresolved toxicities from previous anticancer therapy that have not resolved, or have not stabilized at a new baseline