Lung CancerPhase 1NCT00084799
Monoclonal Antibody Therapy in Treating Patients With Progressive Small Cell Lung Cancer (SCLC)
A Phase 1 study testing monoclonal antibody hu3S193 in people with Lung Cancer, run by Ludwig Institute for Cancer Research at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- What is being tested?
- monoclonal antibody hu3S193
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jul 2004to 20 Dec 2006
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
About this study
Official title: A Multiple-Dose Targeting Study of hu3S193 in Patients With Small Cell Lung Cancer
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).
Read the 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.
- Conditions
- Lung Cancer
- Being tested
- monoclonal antibody hu3S193
- Keywords
- recurrent small cell lung cancer (SCLC)
- Medical subject headings
- Lung Neoplasms, Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
monoclonal antibody hu3S193Biological
| Study group | Role | What they receive |
|---|---|---|
| hu3S193 10 mg/m2 | Experimental | 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). Receives: Biological: monoclonal antibody hu3S193 |
| hu3S193 20 mg/m2 | Experimental | 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). Receives: Biological: monoclonal antibody hu3S193 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days
Secondary outcomes (6)
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.
Measured: 4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)
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.
Measured: 4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)
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.
Measured: 4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)
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.
Measured: 4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)
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).
Measured: 4 weeks (pre-dose, weeks 1, 2, 3, and 4)
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).
Measured: up to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2004 (estimated)
- Study start26 Jul 2004
- Primary completion25 Jan 2006
- Study completion20 Dec 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig Institute for Cancer Research
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Lee M. Krug, MD, Principal investigator, Memorial Sloan Kettering Cancer CenterChaitanya R. Divgi, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00084799
- Sponsor's protocol ID
- LUD2002-015
- Other IDs
- MSKCC 04-012, CDR0000365621
- Status last verified
- Oct 2023
- First submitted
- 10 Jun 2004
- Last updated
- 4 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 10655437Krug 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.
PubMed 17909358
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multiple-Dose Targeting Study of hu3S193 in Patients With Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT00084799
- Acronym / sponsor ID
- LUD2002-015
- Conditions
- Lung Cancer
- Keywords
- recurrent small cell lung cancer (SCLC)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Ludwig Institute for Cancer ResearchUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 26 Jul 2004 (actual)
- Primary completion
- 25 Jan 2006 (actual)
- Study completion
- 20 Dec 2006 (actual)
- First posted
- 11 Jun 2004 (estimated)
- Results
- Posted 8 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| hu3S193 10 mg/m2 | Experimental | Biological: monoclonal antibody hu3S193Patients 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). |
| hu3S193 20 mg/m2 | Experimental | Biological: monoclonal antibody hu3S193Patients 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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).
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| monoclonal antibody hu3S193 | Biological | hu3S193 10 mg/m2, hu3S193 20 mg/m2 |
Primary outcome
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.
Time frame: 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.
6 secondary outcomes
Mean Half-life (T1/2) as Measured by 111In-hu3S193 Radioactivity
Time frame: 4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)
Mean Volume of Distribution of Central Compartment (V1) as Measured by 111In-hu3S193 Radioactivity
Time frame: 4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)
Mean Clearance (CL) as Measured by 111In-hu3S193 Radioactivity
Time frame: 4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)
Mean Area Under the Curve (AUC) as Measured by 111In-hu3S193 Radioactivity
Time frame: 4 weeks (days 1, 2, 3, and 5; weeks 1 and 4)
Immunogenicity of hu3S193 as Measured by the Number of Patients With Human Anti-human Antibodies (HAHA) After Treatment With hu3S193.
Time frame: 4 weeks (pre-dose, weeks 1, 2, 3, and 4)
Number of Patients With Tumor Responses After Treatment With hu3S193 as Measured by RECIST
Time frame: up to 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10655437Therasse 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.
- Results publication: PubMed 17909358Krug 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lee M. Krug, MD principal investigator
Memorial Sloan Kettering Cancer Center
Chaitanya R. Divgi, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing monoclonal antibody hu3S193 in people with Lung Cancer, run by Ludwig Institute for Cancer Research at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00084799, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2023.