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

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00084799
• Other study ID #: LUD2002-015
• Secondary ID: MSKCC 04-012CDR0
• Status: Completed
• Phase: Phase 1
• Start date: July 26, 2004
• Est. completion date: December 20, 2006

Study information

• Verified date: October 2023
• Source: Ludwig Institute for Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 20, 2006
• Est. primary completion date: January 25, 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Biological:
• monoclonal antibody hu3S193

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Ludwig Institute for Cancer Research	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Krug LM, Milton DT, Jungbluth AA, Chen LC, Quaia E, Pandit-Taskar N, Nagel A, Jones J, Kris MG, Finn R, Smith-Jones P, Scott AM, Old L, Divgi C. Targeting Lewis Y (Le(y)) in small cell lung cancer with a humanized monoclonal antibody, hu3S193: a pilot tri — View Citation

Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205. — View Citation

Outcome

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