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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00084799

Enrollment

Registered

2004-06-11

Start date

2004-07-26

Completion date

2006-12-20

Last updated

2023-10-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lung Cancer

Keywords

recurrent small cell lung cancer (SCLC)

Brief summary

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).

Detailed description

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.

Interventions

BIOLOGICALmonoclonal antibody hu3S193

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Small cell lung cancer, pathologically confirmed. Measurable disease, including at least one lesion measuring ≥ 2 cm that has not been previously irradiated. Progression of disease after one, two, or three prior chemotherapy regimens. At least 4 weeks since the last chemotherapy or radiation treatment. Karnofsky performance status ≥ 70% (ECOG 0 or 1). The following laboratory results within the last 2 weeks prior to study day 1: White Blood Cell Count (WBC) ≥ 3,500/mm3; Platelet count ≥ 100 x 10\^9/L; Serum creatinine ≤ 2.0 mg/dL; Serum bilirubin ≤ 2.0 mg/dL; International normalized ratio (INR) ≤ 1.3; Women of childbearing potential with confirmed negative quantitative serum HCG on the day of administration of study agent. Negative stool guaiac test (read by laboratory). Tumor tissue positive for Lewis Y expression.

Exclusion criteria

Clinically significant cardiac disease (New York Heart Association Class III/IV). Uncontrolled brain or leptomeningeal metastases. GI bleed within the preceding 6 months. Patients with history of receiving mouse monoclonal antibody. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment. Women who are pregnant or breast-feeding.

Design outcomes

Primary

Measure	Time frame	Description
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.	28 days	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.

Secondary

Measure	Time frame	Description
Mean Volume of Distribution of Central Compartment (V1) as Measured by 111In-hu3S193 Radioactivity	4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)	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.
Mean Clearance (CL) as Measured by 111In-hu3S193 Radioactivity	4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)	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.
Mean Half-life (T1/2) as Measured by 111In-hu3S193 Radioactivity	4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)	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.
Immunogenicity of hu3S193 as Measured by the Number of Patients With Human Anti-human Antibodies (HAHA) After Treatment With hu3S193.	4 weeks (pre-dose, weeks 1, 2, 3, and 4)	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).
Number of Patients With Tumor Responses After Treatment With hu3S193 as Measured by RECIST	up to 28 days	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).
Mean Area Under the Curve (AUC) as Measured by 111In-hu3S193 Radioactivity	4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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 10 mg/m2. The dose of hu3S193 given on Weeks 1 and 4 was trace-labeled with 6-8 mCi of indium-111 (111In).	5
hu3S193 20 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).	5
Total	10

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Disease Progression	1	0

Baseline characteristics

Characteristic	hu3S193 10 mg/m2	hu3S193 20 mg/m2	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	2 Participants	1 Participants	3 Participants
Age, Categorical Between 18 and 65 years	3 Participants	4 Participants	7 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants	5 Participants	10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	1 Participants	0 Participants	1 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	0 Participants	0 Participants
Race (NIH/OMB) White	4 Participants	4 Participants	8 Participants
Region of Enrollment United States	5 participants	5 participants	10 participants
Sex: Female, Male Female	3 Participants	2 Participants	5 Participants
Sex: Female, Male Male	2 Participants	3 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 5	0 / 5
other Total, other adverse events	5 / 5	5 / 5
serious Total, serious adverse events	1 / 5	0 / 5

Outcome results

Primary

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.

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.

Time frame: 28 days