Recurrent Small Cell Lung Carcinoma
Conditions
Brief 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.
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.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
Given IV
OTHERPharmacological Study
Correlative studies
Sponsors
National Cancer Institute (NCI)
Nektar Therapeutics
Roswell Park Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 18 Week Progression-free Survival Rate | Time from registration to the date of first documented disease progression or death, assessed at 18 weeks | The distribution of time to disease progression will be estimated in each group using the method of Kaplan-Meier at 18 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumor Response Measured With Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | Up to 30 days | 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). |
| Mean Duration of Response | Time from registration to death due to any cause, assessed up to 3 years | The mean duration of response for those participants that responded to treatment by arm. |
| Best Response | Up to 30 days | 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. |
| Median Overall Survival | Time from registration to death due to any cause, assessed up to 3 years | The distribution of survival time was be estimated in each group using the method of Kaplan-Meier. |
| Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0 | Up to 30 days | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| A: Chemo Resistant Group A: chemo resistant - those progressing on first-line therapy \< 3 months after completion of treatment.
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
Laboratory Biomarker Analysis: Correlative studies Pegylated Irinotecan: Given IV Pharmacological Study: Correlative studies | 20 |
| B: Chemo Sensitive Group B: chemo sensitive - those progressing on first-line therapy ≥ 3 months after completion of treatment.
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
Laboratory Biomarker Analysis: Correlative studies
Pegylated Irinotecan: Given IV
Pharmacological Study: Correlative studies | 18 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Physician Decision | 1 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | A: Chemo Resistant | B: Chemo Sensitive | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 7 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 11 Participants | 25 Participants |
| Age, Continuous | 60.5 years STANDARD_DEVIATION 8.7 | 61.9 years STANDARD_DEVIATION 7.9 | 61.2 years STANDARD_DEVIATION 8.3 |
| ECOG performance status Grade 0 | 9 Participants | 8 Participants | 17 Participants |
| ECOG performance status Grade 1 | 11 Participants | 10 Participants | 21 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 20 Participants | 17 Participants | 37 Participants |
| Sex: Female, Male Female | 10 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Male | 10 Participants | 9 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 1 / 18 |
| other Total, other adverse events | 19 / 20 | 17 / 18 |
| serious Total, serious adverse events | 4 / 20 | 4 / 18 |
Outcome results
Primary
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
Population: All treated and eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A: Chemo Resistant | 18 Week Progression-free Survival Rate | 35 percentage of participants |
| B: Chemo Sensitive | 18 Week Progression-free Survival Rate | 72 percentage of participants |
Secondary
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
Population: All treated and eligible patients
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A: Chemo Resistant | Best Response | PR Partial Response/Remission | 4 Participants |
| A: Chemo Resistant | Best Response | PD Progressive Disease | 9 Participants |
| A: Chemo Resistant | Best Response | SD Stable Disease | 6 Participants |
| A: Chemo Resistant | Best Response | NE Not Evaluable | 1 Participants |
| A: Chemo Resistant | Best Response | CR Complete Response/Remission | 0 Participants |
| B: Chemo Sensitive | Best Response | NE Not Evaluable | 2 Participants |
| B: Chemo Sensitive | Best Response | CR Complete Response/Remission | 1 Participants |
| B: Chemo Sensitive | Best Response | PR Partial Response/Remission | 6 Participants |
| B: Chemo Sensitive | Best Response | SD Stable Disease | 7 Participants |
| B: Chemo Sensitive | Best Response | PD Progressive Disease | 2 Participants |
Secondary
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
Population: All treated and eligible patients
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| A: Chemo Resistant | Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0 | Grade 2 | 3 Participants |
| A: Chemo Resistant | Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0 | Grade 4 | 0 Participants |
| A: Chemo Resistant | Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0 | Grade 1 | 7 Participants |
| A: Chemo Resistant | Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0 | Grade 5 | 0 Participants |
| A: Chemo Resistant | Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0 | Grade 3 | 9 Participants |
| A: Chemo Resistant | Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0 | Grade 0 | 1 Participants |
| B: Chemo Sensitive | Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0 | Grade 0 | 0 Participants |
| B: Chemo Sensitive | Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0 | Grade 1 | 1 Participants |
| B: Chemo Sensitive | Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0 | Grade 2 | 6 Participants |
| B: Chemo Sensitive | Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0 | Grade 3 | 9 Participants |
| B: Chemo Sensitive | Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0 | Grade 4 | 1 Participants |
| B: Chemo Sensitive | Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0 | Grade 5 | 1 Participants |
Secondary
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
Population: All participants that responded to treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A: Chemo Resistant | Mean Duration of Response | 5.4 months | Standard Deviation 3.8 |
| B: Chemo Sensitive | Mean Duration of Response | 7.0 months | Standard Deviation 6.8 |
Secondary
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
Population: All treated and eligible patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A: Chemo Resistant | Median Overall Survival | 7.4 months |
| B: Chemo Sensitive | Median Overall Survival | 7.1 months |
Secondary
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
Population: All treated and eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A: Chemo Resistant | Objective Tumor Response Measured With Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | 20 percentage of participants |
| B: Chemo Sensitive | Objective Tumor Response Measured With Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | 39 percentage of participants |