Clinical trial NCT00084799: Monoclonal Antibody Therapy in Treating Patients With Progressive Small Cell Lung Cancer (SCLC)
Official title: A Multiple-Dose Targeting Study of hu3S193 in Patients With Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lung Cancer
Keywords: recurrent small cell lung cancer (SCLC)
Lead sponsor: Ludwig Institute for Cancer Research
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-06-11
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 28 days
Secondary outcomes:
measure: Mean Half-life (T1/2) as Measured by 111In-hu3S193 Radioactivity
timeFrame: 4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)
measure: Mean Volume of Distribution of Central Compartment (V1) as Measured by 111In-hu3S193 Radioactivity
timeFrame: 4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)
measure: Mean Clearance (CL) as Measured by 111In-hu3S193 Radioactivity
timeFrame: 4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)
measure: Mean Area Under the Curve (AUC) as Measured by 111In-hu3S193 Radioactivity
timeFrame: 4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)
measure: Immunogenicity of hu3S193 as Measured by the Number of Patients With Human Anti-human Antibodies (HAHA) After Treatment With hu3S193.
timeFrame: 4 weeks (pre-dose, weeks 1, 2, 3, and 4)
measure: Number of Patients With Tumor Responses After Treatment With hu3S193 as Measured by RECIST
timeFrame: up to 28 days
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Lee M. Krug, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Chaitanya R. Divgi, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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 trial testing two dose levels. J Thorac Oncol. 2007 Oct;2(10):947-52. doi: 10.1097/JTO.0b013e3181560dcc.