Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Lung Neoplasms

Carcinoma

Recurrence

Small Cell Lung Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Small Cell Lung Cancer

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Topoisomerase I Inhibitors

Etirinotecan pegol

Enzyme Inhibitors

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

Pegylated Irinotecan

Pharmacological Study

Hongbin Chen, MD

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.

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.

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

The distribution of time to disease progression will be estimated in each group using the method of Kaplan-Meier at 18 weeks.

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).

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

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.

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

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.

National Cancer Institute (NCI)

Nektar Therapeutics

Roswell Park Cancer Institute

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

A: Chemo Resistant

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

B: Chemo Sensitive

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

ECOG Performance Status: Developed by the Eastern Cooperative Oncology Group GRADE 0 -Fully active, able to carry on all pre-disease performance without restriction, GRADE 1 -Restricted in physically strenuous activity but ambulatory and able to carry out work of light or sedentary nature, GRADE 2 -Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours, GRADE 3 -Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours, GRADE 4 -Completely disabled, GRADE 5 -Dead

ECOG performance status

Senior Administrator, Compliance - Clinical Research Services

18 Week Progression-free Survival Rate

Objective Tumor Response Measured With Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

All participants that responded to treatment

Mean Duration of Response

Best Response

Median Overall Survival

Incidence of Adverse Events, Assessed Using NCI CTCAE v 4.0

Overall Study

Skin and Connective Tissue Diseases

Nervous System Diseases

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Breast Neoplasms

Brain Neoplasms

Breast Diseases

Skin Diseases

Disease Attributes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Patients with non-small cell lung carinoma (NSCLC) will receive pegylated irinotecan intravenously (IV) over 90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.

Patients with small cell lung carinoma (SCLC) will receive pegylated irinotecan intravenously (IV) over 90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.

Patients with metastatic breast cancer (MBC) to brain will receive pegylated irinotecan intravenously (IV) over 90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.

Administered intravenously (IV) at 145 mg/m² as monotherapy once every 21 days (1 cycle)

Joel Neal

This phase 2 trial evaluates how well pegylated irinotecan (NKTR-102) works in treating patients with non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), or breast cancer (mBC) that has spread to the brain and does not respond to treatment. Pegylated irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Primary Objective:

For cohort A and Cohort C, 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 in patients with advanced non-small cell lung cancer (NSCLC) or with metastatic brain cancer (mBC) with refractory brain metastases

Secondary Objectives:

Cohorts A and C:

* To measure the overall disease control rate and response rate for patients receiving study therapy
* To measure the systemic (non-CNS) disease control rate and response rate for patients receiving study therapy
* To observe the progression free survival of the study population
* To observe the overall survival of the study population

Cohort B:

• To observe CNS and systemic disease control in small cell lung cancer (SCLC)

Cohorts A, B and C:

• To determine the safety profile of etirinotecan pegol

Phase 2 Etirinotecan Pegol in Refractory Brain Metastases & Advanced Lung Cancer / Metastatic Breast Cancer

A Phase 2 Study of Etirinotecan Pegol (NKTR-102) in Patients With Refractory Brain Metastases and Advanced Lung Cancer or Metastatic Breast Cancer (MBC)

Central nervous system (CNS) disease control (DC) is defined as a complete response (CR); partial response (PR); or stable disease (SD). The outcome is reported as the number and percentage of participants who achieve DC, a number without dispersion.

Response criteria are as follows. Note that any lesion less than 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.

* CR = Disappearance of all target lesions, sustained for ≥ 4 weeks with no new lesions; clinical condition stable or improved
* PR = ≥ 30% decrease in target lesion LD and no new lesions, sustained for ≥ 4 weeks; clinical condition stable or improved
* PD (progressive disease) = Any of 20% increase in target lesion LD; increase in T2/FLAIR non-enhancing lesions; any new lesions; non-target progression; or clinical deterioration
* SD = Neither PR or PD

Overall disease control (DC) rate is defined as the sum in a cohort of the numbers of participants achieving complete response (CR); partial response (PR); or stable disease (SD), divided by the number of patients in that cohort. For this outcome, "overall" means all body systems, not just the central nervous system (CNS). The outcome is reported as DC rate, a number without dispersion.

Response criteria are as follows. Note that any lesion \<10 mm in longest diameter (LD) is considered unchanged unless there is a ≥3 mm change in the sum of the LDs.

* CR = Disappearance of all target lesions, sustained for ≥4 weeks with no new lesions; clinical condition stable or improved
* PR = ≥30% decrease in target lesion LD \& no new lesions, sustained for ≥ 4 weeks; clinical condition stable or improved
* PD = Any of: 20% increase in target lesion LD; increase in T2/FLAIR non-enhancing lesions; any new lesions; non-target progression; or clinical deterioration
* SD = Neither PR or PD

Overall response by subject (OR) is defined as the lower assessment between the central nervous system response and the systemic response. Response is defined as either complete response (CR) or partial response (PR). The outcome is reported as the number and percentage of participants who achieve OR, a number without dispersion.

Response criteria are as follows. Note that any lesion \< 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.

* CR = Disappearance of all lesions, sustained for ≥ 4 weeks with no new lesions; clinical condition stable or improved
* PR = ≥ 30% decrease in target lesion LD \& no new lesions, sustained for ≥ 4 weeks; clinical condition stable or improved
* PD = Any of: 20% increase in target lesion LD; increase in T2/FLAIR non-enhancing lesions; any new lesions; non-target progression; or clinical deterioration
* SD = Neither PR or PD

Systemic (ie, non-central nervous system) disease control (DC) rate by cohort is defined as the number of patients with complete response (CR) + partial response (PR) + stable disease (SD), divided by the total number of patients. The outcome will be reported as DC rate, a number without dispersion.

Response criteria are as follows. Note that any lesion \< 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.

* CR = Disappearance of all lesions, no new lesions; pathological lymph nodes reduced in short axis to \< 10 mm
* PR = ≥ 30% decrease in sum of lesion diameters; no new lesions; no progression of non-target lesions
* PD = Any of 20% increase in sum of lesion diameters; progression of non-target lesions; new lesions
* SD = Neither CR, PR, nor PD

Systemic (ie, non-central nervous system) response rate by cohort is defined as the number of participants achieving a complete response (CR) or partial response (PR), divided by the number of participants. The outcome will be reported as a number without dispersion.

Response criteria are as follows. Note that any lesion \< 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.

* CR = Disappearance of all target lesions, no new lesions; pathological lymph nodes reduced in short axis to \< 10 mm
* PR = ≥ 30% decrease in sum of lesion diameters; no new lesions; no progression of non-target lesions
* PD = Any of 20% increase in sum of lesion diameters; progression of non-target lesions; new lesions
* SD = Neither CR, PR, nor PD

Progression-free survival (PFS) is defined as the time from the date of start of treatment until disease progression or death. The outcome is reported by cohort as PFS in months, with full range.

Overall survival (OS) is defined as the period remaining alive after the start of treatment. The outcome is reported as the median with full range.

Central nervous system (CNS) disease control (DC) is defined as a complete response (CR); partial response (PR); or stable disease (SD). The outcome is reported as the number and percentage of participants who achieve DC, a number without dispersion.

Response criteria are as follows. Note that any lesion less than 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.

* CR = Disappearance of all target lesions, sustained for ≥ 4 weeks with no new lesions; clinical condition stable or improved
* PR = ≥ 30% decrease in target lesion LD and no new lesions, sustained for ≥ 4 weeks; clinical condition stable or improved
* PD = Any of 20% increase in target lesion LD; increase in T2/FLAIR non-enhancing lesions; any new lesions; non-target progression; or clinical deterioration
* SD = Neither PR or PD

Toxicity, defined as related adverse events, is reported as the total number of events experienced by the participants in each cohort, a number without dispersion. Related is defined as meaning possibly, probably, or definitely related to the study drug.

ASSISTANT PROFESSOR OF MEDICINE

Patients with non-small cell lung carinoma (NSCLC) will receive pegylated irinotecan intravenously (IV) over 90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.

Pegylated Irinotecan: Administered intravenously (IV) at 145 mg/m² as monotherapy once every 21 days (1 cycle)

Cohort A - Pegylated Irinotecan to Treat NSCLC

Patients with small cell lung carinoma (SCLC) will receive pegylated irinotecan intravenously (IV) over 90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.

Pegylated Irinotecan: Administered intravenously (IV) at 145 mg/m² as monotherapy once every 21 days (1 cycle)

Cohort B - Pegylated Irinotecan to Treat SCLC

Patients with metastatic breast cancer (MBC) to brain will receive pegylated irinotecan intravenously (IV) over 90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.

Pegylated Irinotecan: Administered intravenously (IV) at 145 mg/m² as monotherapy once every 21 days (1 cycle)

Cohort C - Pegylated Irinotecan to Treat mBC

Ethnicity (NIH/OMB)

United States

Region of Enrollment

Joel W. Neal, MD PhD, Assistant Professor of Medicine (Oncology)

Cohort B (metastatic small cell lung cancer, SCLC) is excluded per protocol from this outcome.

Central Nervous System (CNS) Disease Control Rate (Cohort A and C)

Cohort C - Pegylated Irinotecan to treat mBC Patients with metastatic breast cancer (MBC) to brain will receive pegylated irinotecan intravenously (IV) over 90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.

Pegylated Irinotecan: Administered intravenously (IV) at 145 mg/m² as monotherapy once every 21 days (1 cycle)

Overall Disease Control Rate (Cohort A and C)

Overall Response Rate (Cohort A and C)

Systemic (Non-CNS) Disease Control Rate (Cohort A and C)

Systemic (Non-CNS) Response Rate (Cohort A and C)

Progression-free Survival (PFS) (Cohort A and C)

Overall Survival (Cohort A and C)

This outcome was restricted by protocol to Cohort B.

Central Nervous System (CNS) Disease Control (Cohort B)

Systemic Disease Control (Cohort B)

Related Adverse Events (Toxicity)

Patients with non-small cell lung carinoma (NSCLC) will receive pegylated irinotecan NKTR 102 IV over 90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.

Pegylated Irinotecan: Administered intravenously (IV) at 145 mg/m² as monotherapy once every 21 days (1 cycle)

Patients with small cell lung carinoma (SCLC) will receive pegylated irinotecan NKTR 102 IV over 90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.

Pegylated Irinotecan: Administered intravenously (IV) at 145 mg/m² as monotherapy once every 21 days (1 cycle)

Patients with metastatic breast cancer (MBC) to brain will receive pegylated irinotecan NKTR 102 IV over 90 minutes every 21 days in the absence of disease progression or unacceptable toxicity.

Pegylated Irinotecan: Administered intravenously (IV) at 145 mg/m² as monotherapy once every 21 days (1 cycle)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pegylated Irinotecan NKTR 102 in Treating Patients With Relapsed Small Cell Lung Cancer	NCT01876446	Recurrent Small...	Laboratory Biom... Pegylated Irino... Pharmacological...	18 Years -	Roswell Park Cancer Institute
Phase 2 Etirinotecan Pegol in Refractory Brain Metastases & Advanced Lung Cancer / Metastatic Breast Cancer	NCT02312622	Stage IV Non-sm... Recurrent Non-s... Extensive-stage... Recurrent Small... Tumors Metastat... Metastatic Brea...	Pegylated Irino...	18 Years -	Stanford University
Phase 2 Etirinotecan Pegol in Refractory Brain Metastases & Advanced Lung Cancer / Metastatic Breast Cancer	NCT02312622	Stage IV Non-sm... Recurrent Non-s... Extensive-stage... Recurrent Small... Tumors Metastat... Metastatic Brea...	Pegylated Irino...	18 Years -	Stanford University
Phase 2 Etirinotecan Pegol in Refractory Brain Metastases & Advanced Lung Cancer / Metastatic Breast Cancer	NCT02312622	Stage IV Non-sm... Recurrent Non-s... Extensive-stage... Recurrent Small... Tumors Metastat... Metastatic Brea...	Pegylated Irino...	18 Years -	Stanford University

Spots Global Cancer Trial Database for pegylated irinotecan