Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Skin and Connective Tissue Diseases

Nervous System Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Breast Neoplasms

Recurrence

Small Cell Lung Carcinoma

Carcinoma

Brain Neoplasms

Breast Diseases

Skin Diseases

Disease Attributes

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Small Cell Lung Cancer

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Etirinotecan pegol

Topoisomerase I Inhibitors

Enzyme Inhibitors

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)

Pegylated Irinotecan

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.

Nektar Therapeutics

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

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (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)

Overall Study

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunologic Factors

Patients with small cell lung cancer tumors confirmed to have Lewis Y expression were enrolled to receive 4 weekly injections of hu3S193 at a dose of 10 mg/m2. The dose of hu3S193 given on Weeks 1 and 4 was trace-labeled with 6-8 millicurie (mCi) of indium-111 (111In).

Patients with small cell lung cancer tumors confirmed to have Lewis Y expression were enrolled to receive 4 weekly injections of hu3S193 at a dose of 20 mg/m2. The dose of hu3S193 given on Weeks 1 and 4 was trace-labeled with 6-8 millicurie (mCi) of indium-111 (111In).

monoclonal antibody hu3S193

Lee M. Krug, MD

Chaitanya R. Divgi, MD

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: This phase I trial is studying the side effects of monoclonal antibody therapy in treating patients with progressive small cell lung cancer (SCLC).

OBJECTIVES:

Primary

* Determine the targeting, tissue distribution, and pharmacokinetics of monoclonal antibody hu3S193 in patients with progressive small cell lung cancer (SCLC).

Secondary

* Determine the immunogenicity of of monoclonal antibody hu3S193 in patients with progressive small cell lung cancer (SCLC).
* Determine tumor response of monoclonal antibody hu3S193 in patients with progressive small cell lung cancer (SCLC).
* Determine the safety of tof monoclonal antibody hu3S193 in patients with progressive small cell lung cancer (SCLC).

OUTLINE: This is an open-label, pilot study.

Patients received monoclonal antibody hu3S193 (mAb hu3S193) intravenously (IV) over 30 minutes on day 1 of weeks 1-4. Patients also received indium-111 (111In) radiolabeled hu3S193 IV over 30 minutes on day 1 of weeks 1 and 4 and then underwent gamma camera imaging. Treatment continued in the absence of disease progression or unacceptable toxicity.

Patients were followed at 1 and 4 weeks, every 3 months for 1 year, and then every 6-12 months thereafter.

Monoclonal Antibody Therapy in Treating Patients With Progressive Small Cell Lung Cancer (SCLC)

A Multiple-Dose Targeting Study of hu3S193 in Patients With Small Cell Lung Cancer

Gamma camera imaging, including planar scans and single-photon emission computed tomography (SPECT) scans, were carried out immediately following completion of infusion and on two subsequent occasions during the next 6 days after the infusions of 111In-hu3S193 on weeks 1 and 4. A pretreatment FDG-positron emission tomography PET/CT scan was performed within 2 weeks of study entry per standard clinical methods for comparison with gamma camera imaging. FDG-PET/ CT scans and 111In planar and SPECT scans were evaluated for extent of disease and antibody targeting, respectively. Lesions on FDG-PET/CT scans were considered positive if uptake of radiotracer was visually greater than surrounding tissue, with a standard uptake value greater than 3.

Blood samples for analysis of radioactivity and serum concentration of hu3S193 were obtained immediately before and 5, 60, and 120 minutes post-infusion, before and after imaging on day 2, and on days 3 and 5 after completion of the 111In-hu3S193 infusion in weeks 1 and 4. Pharmacokinetics was calculated using WinNonLin (Pharsight Co., Mountain View, CA). A two-compartment model was fitted to individually labeled infusions for each patient using unweighted nonlinear least squares to calculate pharmacokinetic parameters.

Blood samples to measure human anti-human antibody (HAHA) assessments were obtained at baseline and each week before hu3S193 dosing. Measurement of immune responses to hu3S193 in patient blood samples was analyzed using a BIACORE (Piscataway, NJ) instrument using surface plasmon resonance (SPR).

Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Per RECIST, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions (no evaluable disease); partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria (Therasse P et al. 2000).

National Cancer Institute (NCI)

Ludwig Institute for Cancer Research

All adverse events (AEs) occurring during the study were to be documented in the source records and on the respective AE Case Report Form (CRF). Adverse events which occurred prior to the first administration of study drug were documented on the Pre-existing symptoms CRF page, thereafter, they were documented on the Adverse Event CRF page. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) Scale (Version 3.0, published April 16, 2003).

Patients with small cell lung cancer tumors confirmed to have Lewis Y expression were enrolled to receive 4 weekly injections of hu3S193 at a dose of 10 mg/m2. The dose of hu3S193 given on Weeks 1 and 4 was trace-labeled with 6-8 mCi of indium-111 (111In).

hu3S193 10 mg/m2

Patients with small cell lung cancer tumors confirmed to have Lewis Y expression were enrolled to receive 4 weekly injections of hu3S193 at a dose of 20 mg/m2. The dose of hu3S193 given on Weeks 1 and 4 was trace-labeled with 6-8 mCi of indium-111 (111In).

hu3S193 20 mg/m2

All patients who received at least one dose of hu3S193.

Jonathan Skipper PhD

Patients who received at least one dose of hu3S193.

Confirmation of Tumor Targeting as Measured by the Number of Patients With Assessable Lesions Greater Than or Equal to 2 cm Measured by FDG-PET and SPECT Imaging.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
Monoclonal Antibody Therapy in Treating Patients With Progressive Small Cell Lung Cancer (SCLC)	NCT00084799	Lung Cancer	monoclonal anti...	18 Years -	Ludwig Institute for Cancer Research

Spots Global Cancer Trial Database for recurrent small cell lung cancer (sclc)