Pegylated Irinotecan NKTR 102 in Treating Patients With Refractory Brain Metastasis From Non-small Cell Lung Cancer or Small Cell Lung Cancer
Conditions
Extensive Stage Small Cell Lung Cancer - Recurrent Non-small Cell Lung Cancer - Recurrent Small Cell Lung Cancer - Stage IV Non-small Cell Lung Cancer - Tumors Metastatic to Brain
Conditions: official terms
Carcinoma, Non-Small-Cell Lung - Lung Neoplasms - Small Cell Lung Carcinoma
Study Type
Interventional
Study Phase
Phase 2
Study Design
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: pegylated irinotecan NKTR 102 Type: Drug
Name: laboratory biomarker analysis Type: Other
Overall Status
Recruiting
Summary
This phase II trial studies how well pegylated irinotecan NKTR 102 works in treating patients with non-small cell lung cancer or small cell lung cancer that has spread to the brain and does not respond to treatment. Pegylated irinotecan NKTR 102 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVES:

I. To determine the central nervous system (CNS) disease control rate (number of patients with stable disease or partial response or complete response/total number of treated patients) at 12 weeks following treatment with etirinotecan pegol (pegylated irinotecan NKTR 102) in patients with advanced non-small cell lung cancer (NSCLC) with refractory brain metastases. (Cohort A)

SECONDARY OBJECTIVES:

I. To measure the overall disease control rate and response rate for patients receiving study therapy. (Cohort A) II. To measure the systemic (non CNS) disease control rate and response rate for patients receiving study therapy. (Cohort A) III. To observe the progression free survival of the study population. (Cohort A) IV. To observe the overall survival of the study population. (Cohort A) V. To observe CNS and systemic disease control in small cell lung cancer (SCLC). (Cohort B) VI. To determine the safety profile of etirinotecan pegol (NKTR 102). (Cohorts A and B)

OUTLINE:

Patients receive pegylated irinotecan NKTR 102 intravenously (IV) over 90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: 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)

- 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 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 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 investigator believes that this study therapy represents a reasonable alternative to such treatments

- Patients must have measurable CNS disease, either previously untreated (not counting systemic therapy), or progressed following previous radiation treatment; 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

- Two or three 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

- 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 leptomeningeal disease, unless prospective permission for enrollment is granted from the sponsor and the PI

- Patients may not have had radiotherapy within 14 days prior to initiation of study treatment

- 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 who are using chronic anti diarrheal supportive care (more than 3 days/week) to control diarrhea in the 28 days prior to first dose of investigational drug

- 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
Location
Stanford University Hospitals and Clinics
Stanford, California, United States
Status: Recruiting
Contact: Sophie Bertrand - 650-723-4467 - sophieb@stanford.edu
Start Date
January 2015
Completion Date
January 2018
Sponsors
Stanford University
Source
Stanford University
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page