Pegylated Irinotecan NKTR 102 in Treating Patients With Relapsed Small Cell Lung Cancer

Study Overview
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Brief Summary
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This phase II trial studies how well pegylated irinotecan NKTR 102 works in treating patients with small cell lung cancer that has returned after a period of improvement. Pegylated irinotecan NKTR 102 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the 18-week progression free survival (PFS) rate of relapsed small cell lung cancer (SCLC) patients treated with NKTR-102 (pegylated irinotecan NKTR 102). SECONDARY OBJECTIVES: I. To evaluate the objective response rate. II. To evaluate the duration of response. III. To evaluate the overall survival. IV. To evaluate the toxicity of NKTR-102 in this patient population. TERTIARY OBJECTIVES: I. To explore the correlation between UDP glucuronosyltransferase 1 family, polypeptide A cluster (UGTIA1) polymorphisms and NKTR-102 toxicities. OUTLINE: Patients receive pegylated irinotecan NKTR 102 intravenously (IV) over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Official Title
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A Phase II Study of Single Agent Topoisomerase-I Inhibitor Polymer Conjugate, Etirinotecan Pegol (NKTR-102), in Patients With Relapsed Small Cell Lung Cancer

Conditions
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Recurrent Small Cell Lung Carcinoma

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Drug: Pegylated Irinotecan
* Other: Pharmacological Study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent granted prior to initiation of any study-specific screening procedures, given with the understanding that the patient has the right to withdraw from the study at any time, without prejudice Histologic or cytologic diagnosis of SCLC (Note: patients with mixed histology are not eligible) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Presence of measurable disease defined as >= 1 lesion whose longest diameter can be accurately measured as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) Previously treated SCLC with only one prior treatment regimen (cyclophosphamide/doxorubicin/vincristine [CAV] alternating with etoposide/cisplatin [EP] is acceptable) Resolution of all acute toxic effects of prior chemotherapy, radiotherapy, hormonal therapy, or surgery to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade =< 1, except for diarrhea (which must be grade 0 without supportive antidiarrheal medications) and alopecia (any grade) Platelet count >= 100 x 10^9/L Hemoglobin (Hgb) >= 9 gm/dL Absolute neutrophil count (ANC) >= 1500/uL Serum creatinine =< 1.5 mg/dL or creatinine clearance > 45 mL/min; use either measured or calculated with Cockcroft-Gault formula Serum total bilirubin =< 1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN or =< 5 x ULN if caused by liver metastasis Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug; male and female subjects of child-bearing potential must agree to use double-barrier contraceptive measures, or avoidance of intercourse during the study and for 6 months after last investigational drug dose received Exclusion Criteria: Previous anti-cancer chemotherapy, immunotherapy or investigational agents < 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to the first day of study defined treatment; palliative radiation < 2 weeks, biological therapy within 2 weeks, hormonal therapy within 1 week prior to day 1 cycle 1 Prior treatment with a topoisomerase-I inhibitor (e.g., topotecan, irinotecan) Prior malignancy except for non-melanoma skin cancer and carcinoma in situ, unless diagnosed and definitively treated more than 5 years prior to enrollment Substance abuse, medical, psychological or social conditions that may, in the opinion of the Investigator, interfere with the patient's participation in the study or evaluation of the study results Known human immunodeficiency virus (HIV) infection Pregnancy or breast-feeding Concurrent administration or received cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers or inhibitors within 2 weeks prior to the first day of study drug treatment Patients with 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 study entry Major surgery < 4 weeks or minor surgery (e.g. talc pleurodesis, excisional biopsy, etc) < 2 weeks prior to the first day of study defined treatment Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy); brain imaging is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Unwilling or unable to follow protocol requirements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (pegylated irinotecan NKTR 102)<br>Patients receive pegylated irinotecan NKTR 102 IV over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Pegylated Irinotecan<br>* Given IV<br>* Other names: PEG-Irinotecan;Other: Pharmacological Study<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 18 Week Progression-free Survival Rate | The distribution of time to disease progression will be estimated in each group using the method of Kaplan-Meier at 18 weeks. | Time from registration to the date of first documented disease progression or death, assessed at 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response Measured With Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | Objective tumor response will be tabulated overall (and by dose level if appropriate). Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in the cohorts (overall and by tumor group). | Up to 30 days | 
| Mean Duration of Response | The mean duration of response for those participants that responded to treatment by arm. | Time from registration to death due to any cause, assessed up to 3 years | 
| Best Response | Count of participants by best response, defined as best objective status recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since treatment started), measured by RECIST 1.1 Tumor response is defined as a complete response (CR) or partial response (PR) by RECIST 1.1 criteria, which will be evaluated by CT scan every other cycle. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Up to 30 days | 
| Median Overall Survival | The distribution of survival time was be estimated in each group using the method of Kaplan-Meier. | Time from registration to death due to any cause, assessed up to 3 years | 
| Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0 | Count of participants by maximum graded according to NCI CTCAE v 4.0 of any adverse event by arm. Please refer to the adverse event reporting for more detail. | Up to 30 days |