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

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

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Small Cell Lung Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Pegylated Irinotecan

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Rochester, New York, United States, 14621
      • Rochester General Hospital
    • Rochester, New York, United States, 14625
      • Linden Oaks Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (pegylated irinotecan NKTR 102); 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; Correlative studies; Other: Pharmacological Study; Correlative studies; Drug: Pegylated Irinotecan; Given IV; Other Names: PEG-Irinotecan; NKTR 102

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: National Cancer Institute (NCI); Nektar Therapeutics
• Investigators: Principal Investigator: Hongbin Chen, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2013
• Primary Completion (Actual): July 18, 2017
• Study Completion (Actual): February 24, 2020

Study Registration Dates

• First Submitted: June 10, 2013
• First Submitted That Met QC Criteria: June 10, 2013
• First Posted (Estimate): June 12, 2013

Study Record Updates

• Last Update Posted (Actual): March 17, 2020
• Last Update Submitted That Met QC Criteria: March 3, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: I 225612 (Other Identifier: Roswell Park Cancer Institute); P30CA016056 (U.S. NIH Grant/Contract); NCI-2013-01142 (Registry Identifier: CTRP (Clinical Trial Reporting Program))