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CompletedNCT01876446Updated Mar 17, 2020Results posted

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

A Phase 2 interventional study of Laboratory Biomarker Analysis and Pegylated Irinotecan in Recurrent Small Cell Lung Carcinoma, sponsored by Roswell Park Cancer Institute. Completed at 3 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-03-17.

Sponsored by Roswell Park Cancer Institute · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
38
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Recurrent Small Cell Lung Carcinoma
03

In context

Small Cell Lung Carcinoma

1,203 studies on the registry are indexed under Small Cell Lung Carcinoma; 342 are open to participants now.

This study's enrollment of 38 is below the median of 56 across 1,031 interventional studies indexed under Small Cell Lung Carcinoma.

Browse Small Cell Lung Carcinoma studies →

Lead sponsor

Roswell Park Cancer Institute is the lead sponsor of 412 studies on the registry; 62 are open to participants now.

Of its 38 completed or terminated interventional studies of FDA-regulated products, 21 (55%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
38 participants (actual)

Study arms

  • 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 · Drug: Pegylated Irinotecan · Other: Pharmacological Study

Interventions

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • DrugPegylated Irinotecan

    Given IV

    Also known as: NKTR 102, PEG-Irinotecan

  • OtherPharmacological Study

    Correlative studies

06

What researchers measure

Primary outcomes

  1. 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 frame: Time from registration to the date of first documented disease progression or death, assessed at 18 weeks

Secondary outcomes

  1. 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).

    Time frame: Up to 30 days

  2. Mean Duration of Response

    The mean duration of response for those participants that responded to treatment by arm.

    Time frame: Time from registration to death due to any cause, assessed up to 3 years

  3. 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.

    Time frame: Up to 30 days

  4. Median Overall Survival

    The distribution of survival time was be estimated in each group using the method of Kaplan-Meier.

    Time frame: Time from registration to death due to any cause, assessed up to 3 years

  5. 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.

    Time frame: Up to 30 days

07

Results

Posted Sep 6, 2019

Participant flow

Participant flow — Overall Study
MilestoneA: Chemo ResistantB: Chemo Sensitive
Started2018
Completed1812
Not completed26
Withdrew: Death01
Withdrew: Withdrawal by subject12
Withdrew: Physician decision13

Outcome measures

Primary18 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 frame:
Time from registration to the date of first documented disease progression or death, assessed at 18 weeks
Reported as:
Number · percentage of participants
18 Week Progression-free Survival Rate
percentage of participantsA: Chemo ResistantB: Chemo Sensitive
18 Week Progression-free Survival Rate35 (16 to 55)72 (46 to 87)
SecondaryObjective 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).

Time frame:
Up to 30 days
Reported as:
Number · percentage of participants
Objective Tumor Response Measured With Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
percentage of participantsA: Chemo ResistantB: Chemo Sensitive
Objective Tumor Response Measured With Response Evaluation Criteria in Solid Tumors (RECIST) 1.120 (6 to 44)39 (17 to 64)
SecondaryMean Duration of Response

The mean duration of response for those participants that responded to treatment by arm.

Time frame:
Time from registration to death due to any cause, assessed up to 3 years
Reported as:
Mean · months
Mean Duration of Response
monthsA: Chemo ResistantB: Chemo Sensitive
Mean Duration of Response5.4 ± 3.87.0 ± 6.8
SecondaryBest 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.

Time frame:
Up to 30 days
Reported as:
Count of participants · Participants
Best Response
ParticipantsA: Chemo ResistantB: Chemo Sensitive
CR Complete Response/Remission01
PR Partial Response/Remission46
SD Stable Disease67
PD Progressive Disease92
NE Not Evaluable12
SecondaryMedian Overall Survival

The distribution of survival time was be estimated in each group using the method of Kaplan-Meier.

Time frame:
Time from registration to death due to any cause, assessed up to 3 years
Reported as:
Median · months
Median Overall Survival
monthsA: Chemo ResistantB: Chemo Sensitive
Median Overall Survival7.4 (2.9 to 11.7)7.1 (4.8 to 14.7)
SecondaryIncidence 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.

Time frame:
Up to 30 days
Reported as:
Count of participants · Participants
Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0
ParticipantsA: Chemo ResistantB: Chemo Sensitive
Grade 171
Grade 236
Grade 399
Grade 401
Grade 501
Grade 010

Adverse events

Collected over From time of Cycle 1 Day 1 until 30 days after receiving last dose of study drug, an average of 4 months (range 1 to 21 months).. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
A: Chemo Resistant0/20 (0%)4/20 (20%)19/20 (95%)
B: Chemo Sensitive1/18 (5.6%)4/18 (22.2%)17/18 (94.4%)
Most frequent serious events
Most frequent serious events
EventA: Chemo ResistantB: Chemo Sensitive
DiarrhoeaGastrointestinal disorders2/200/18
Pericardial effusionCardiac disorders0/201/18
Gastric ulcer perforationGastrointestinal disorders0/201/18
Hip fractureInjury, poisoning and procedural complications0/201/18
Muscular weaknessMusculoskeletal and connective tissue disorders0/201/18
DiverticulitisInfections and infestations1/200/18
Renal failure acuteRenal and urinary disorders1/200/18
DyspnoeaRespiratory, thoracic and mediastinal disorders1/200/18
Most frequent other events
Showing 10 of 70
Most frequent other events
EventA: Chemo ResistantB: Chemo Sensitive
DiarrhoeaGastrointestinal disorders10/2012/18
NauseaGastrointestinal disorders7/2010/18
FatigueGeneral disorders7/207/18
Decreased appetiteMetabolism and nutrition disorders3/207/18
Weight decreasedInvestigations7/204/18
VomitingGastrointestinal disorders6/205/18
White blood cell count decreasedInvestigations6/203/18
AnaemiaBlood and lymphatic system disorders5/203/18
Abdominal painGastrointestinal disorders3/204/18
HaemoglobinInvestigations1/204/18

Baseline characteristics

All treated and eligible patients

Age, Categorical
Age, Categorical(Participants)A: Chemo ResistantB: Chemo SensitiveTotal
<=18 years000
Between 18 and 65 years141125
>=65 years6713
Age, Continuous
Age, Continuous(years)A: Chemo ResistantB: Chemo SensitiveTotal
Mean60.5 ± 8.761.9 ± 7.961.2 ± 8.3
Sex: Female, Male
Sex: Female, Male(Participants)A: Chemo ResistantB: Chemo SensitiveTotal
Female10919
Male10919
Race (NIH/OMB)
Race (NIH/OMB)(Participants)A: Chemo ResistantB: Chemo SensitiveTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American000
White201737
More than one race000
Unknown or Not Reported011
ECOG performance status
ECOG performance status(Participants)A: Chemo ResistantB: Chemo SensitiveTotal
Grade 09817
Grade 1111021
08

Study locations

3 sites
  • Roswell Park Cancer Institute
    Buffalo, New York 14263, United States
  • Rochester General Hospital
    Rochester, New York 14621, United States
  • Linden Oaks Medical Campus
    Rochester, New York 14625, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Jan 27, 2017

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 17, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01876446
Lead sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI), Nektar Therapeutics
Responsible party
Sponsor
First posted
Jun 12, 2013
Start date
Aug 29, 2013
Primary completion
Jul 18, 2017
Completion
Feb 24, 2020
Results posted
Sep 6, 2019
Last update
Mar 17, 2020

Study contacts

Hongbin Chen, MD
principal investigator · Roswell Park Cancer Institute

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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