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NCT00084799

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

Completed Phase 1 Results posted Last updated 4 October 2023
What this trial tests

Phase 1 trial testing monoclonal antibody hu3S193 in Lung Cancer in 10 participants. Completed in 20 December 2006.

Timeline
26 July 2004
Primary endpoint
25 January 2006
20 December 2006

Quick facts

Lead sponsorLudwig Institute for Cancer Research
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment10
Start date26 July 2004
Primary completion25 January 2006
Estimated completion20 December 2006
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Ludwig Institute for Cancer Research

Who can join

18 and older, any sex, with Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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. Primary · 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/

GroupValue95% CI
hu3S193 10 mg/m25
hu3S193 20 mg/m25
Mean Half-life (T1/2) as Measured by 111In-hu3S193 Radioactivity Secondary · 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.

T½α
GroupValue95% CI
hu3S193 10 mg/m213.28± 11.02
hu3S193 20 mg/m27.45± 7.06
T½β
GroupValue95% CI
hu3S193 10 mg/m2126.22± 35.35
hu3S193 20 mg/m2129.60± 51.93
Mean Volume of Distribution of Central Compartment (V1) as Measured by 111In-hu3S193 Radioactivity Secondary · 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.

GroupValue95% CI
hu3S193 10 mg/m23040.78± 565.38
hu3S193 20 mg/m23468.07± 686.79
Mean Clearance (CL) as Measured by 111In-hu3S193 Radioactivity Secondary · 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.

GroupValue95% CI
hu3S193 10 mg/m228.83± 15.32
hu3S193 20 mg/m230.81± 10.18
Mean Area Under the Curve (AUC) as Measured by 111In-hu3S193 Radioactivity Secondary · 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.

GroupValue95% CI
hu3S193 10 mg/m2859.97± 347.19
hu3S193 20 mg/m21327.00± 465.47
Immunogenicity of hu3S193 as Measured by the Number of Patients With Human Anti-human Antibodies (HAHA) After Treatment With hu3S193. Secondary · 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).

GroupValue95% CI
hu3S193 10 mg/m20
hu3S193 20 mg/m20
hu3S193 10 mg/m25
hu3S193 20 mg/m25
Number of Patients With Tumor Responses After Treatment With hu3S193 as Measured by RECIST Secondary · 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).

GroupValue95% CI
hu3S193 10 mg/m20
hu3S193 20 mg/m20
hu3S193 10 mg/m20
hu3S193 20 mg/m20
hu3S193 10 mg/m20
hu3S193 20 mg/m20
hu3S193 10 mg/m25
hu3S193 20 mg/m25

Adverse events — posted to ClinicalTrials.gov

Time frame: up to 8 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

hu3S193 10 mg/m2
Serious: 1/5 (20%)
Deaths: 0/5
hu3S193 20 mg/m2
Serious: 0/5 (0%)
Deaths: 0/5

Serious adverse events (1 terms)

ReactionSystemhu3S193 10 mg/m2hu3S193 20 mg/m2
Pleural effusionRespiratory, thoracic and mediastinal disorders
Other adverse events (34 terms — click to expand)

ReactionSystemhu3S193 10 mg/m2hu3S193 20 mg/m2
HemoglobinInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
HyperglycaemiaMetabolism and nutrition disorders
Blood creatinineInvestigations
VomitingGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
HyperkalaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
NauseaGastrointestinal disorders
Alanine aminotransferaseInvestigations
Aspartate aminotransferaseInvestigations
Blood alkaline phosphataseInvestigations
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
HyperbillirubinemiaHepatobiliary disorders
LymphopeniaBlood and lymphatic system disorders
Platelet countInvestigations
White blood cell countInvestigations
HypokalaemiaMetabolism and nutrition disorders
International normalised ratioInvestigations
Activated partial thromboplastin timeInvestigations
Blood creatine phosphokinaseInvestigations
Chest painGeneral disorders
ConstipationGastrointestinal disorders
Dry mouthGastrointestinal disorders
Dry skinSkin and subcutaneous tissue disorders
Skin exfoliationSkin and subcutaneous tissue disorders
HeadacheNervous system disorders
HypernatraemiaMetabolism and nutrition disorders
HypertensionVascular disorders
Radiation skin injuryInjury, poisoning and procedural complications
UrticariaSkin and subcutaneous tissue disorders
Decreased appetiteMetabolism and nutrition disorders

Most-reported serious reactions: Pleural effusion.

Data from ClinicalTrials.gov NCT00084799 adverse events section.

Sponsor's own description

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).

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Glycosylation: mechanisms, biological functions and clinical implications.
    He M, Zhou X, Wang X. · · 2024 · cited 248× · PMID 39098853 · DOI 10.1038/s41392-024-01886-1
  2. Targeting Tumor Glycans for Cancer Therapy: Successes, Limitations, and Perspectives.
    Berois N, Pittini A, Osinaga E. · · 2022 · cited 96× · PMID 35158915 · DOI 10.3390/cancers14030645
  3. Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy.
    Boyero L, Sánchez-Gastaldo A, Alonso M, Noguera-Uclés JF, et al · · 2020 · cited 78× · PMID 33322522 · DOI 10.3390/cancers12123729
  4. T-cell-associated cellular immunotherapy for lung cancer.
    Li K, Zhang Q, Zhang Y, Yang J, et al · · 2015 · cited 15× · PMID 25381064 · DOI 10.1007/s00432-014-1867-0
  5. Advancements in the Understanding of Small-Cell Neuroendocrine Cervical Cancer: Where We Stand and What Lies Ahead.
    Wang Y, Qiu H, Lin R, Hong W, et al · · 2024 · cited 5× · PMID 38793044 · DOI 10.3390/jpm14050462

Verify or expand the search:

Other trials of monoclonal antibody hu3S193

Trials testing the same drug.

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Other Ludwig Institute for Cancer Research trials

Trials by the same sponsor.

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