NeoplasmsPhase 1NCT00293215
Biodistribution Study of CMD-193 in Patients With Advanced Tumours Expressing the Lewis-Y Antigen
A Phase 1 study testing 111-Indium-CMD-193 and CMD-193 in people with Neoplasms, run by Ludwig Institute for Cancer Research at 2 sites in Australia.
Trial summary
This was a Phase 1 dose-escalation study of CMD-193, a humanized monoclonal antibody linked to the toxin calicheamicin, in subjects with advanced tumors expressing the Lewis-Y antigen. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- 111-Indium-CMD-193 and CMD-193
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 2 sitesAustralia
- Study dates
- Feb 2006to May 2007
- 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
- Signed and dated Institutional Review Board (IRB)-approved informed consent before any protocol-specific screening procedures were performed.
- Histologically confirmed malignant solid tumor that had progressed following standard therapy, or for which no standard effective treatment was available.
- Tumor expression of Lewis-Y antigen (≥20% tumor cells positive for Lewis-Y by immunohistochemistry assay).
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST), including the presence of at least one measurable lesion at least 2 cm in size suitable for 18F-FDG PET imaging.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy ≥ 18 weeks.
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- Age ≥18 years.
- Recovery to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) ≤ Grade 1 toxicity from any significant effects of prior surgery, radiation therapy, and cancer therapy (except alopecia).
- Renal test: serum creatinine ≤ 1.5 x upper limit of normal (ULN).
- Hepatic tests: alanine aminotransferase (ALT) levels ≤2.5 x ULN and total bilirubin ≤1.5 x ULN.
- Pancreatic tests: amylase ≤1.5 x ULN and lipase ≤ 1.5 x ULN.
- Bone marrow tests: absolute neutrophil count (ANC) of ≥1500 mm^3 (≥1.5 x 10^9/L) and platelet count of ≥ 150,000/mm^3 (≥150 x 10^9/L).
- For women of childbearing potential, a negative serum pregnancy test result no longer than 48 hours before the first dose of CMD-193. A woman of childbearing potential was one who was biologically capable of becoming pregnant. This included women who were using contraceptives or whose sexual partners were either sterile or using contraceptives.
- All subjects who were not surgically sterile or postmenopausal must have agreed and committed to the use of a reliable method of birth control for the duration of the study and for 28 days after the last dose of CMD-193.
- Willingness of female subjects to refrain from breastfeeding infants during the study or within 28 days after the last dose of CMD-193.
Who cannot join
- Chemotherapy, radiation therapy, other cancer therapy, or investigational agents within 21 days of the first dose of CMD-193 (42 days if the previous chemotherapy included nitrosoureas or mitomycin C).
- Symptomatic or clinically active central nervous system (CNS) metastases. Subjects who had prior treatment with radiotherapy or surgical resection for CNS metastases were permitted if CNS metastases had remained stable and not required any treatment for at least 3 months prior to the first dose of CMD-193.
- Significant prior allergic reaction to recombinant human or murine proteins.
- History of cirrhosis, current or chronic hepatitis B or C infections, or other significant active liver disease.
- Unstable or serious concurrent medical conditions. Examples included, but were not limited to, bleeding gastric ulcers, gastrointestinal bleeding, hepatitis, significant disorders of the immune system (eg, systemic lupus erythematosus), pancreatitis, congestive heart failure, serious active infections (e.g. requiring antibiotics or antiviral agents), unstable angina, recent myocardial infarction (within 6 months of screening), ongoing maintenance therapy for life-threatening ventricular arrhythmia, or uncontrolled major seizure disorder.
- Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
- Any other condition that, in the Investigator's judgment, would have substantially increased the risk associated with the subject's participation in this study.
Trial locations and contacts
2 sites in 1 country.
Australia2 sites
Ludwig Institute Tumor Targeting Program, Austin Health
Heidelberg (Melbourne), Victoria, 3084
Cancer Care Services, Dept. of Medical Oncology, Royal Brisbane and Women's Hospital
Herston, Queensland, 4209
About this study
Official title: Phase I Biodistribution Study of 111-Indium-CMD-193 in Patients With Advanced Tumours Expressing the Lewis-Y Antigen
This was a Phase 1 dose-escalation study of CMD-193, a humanized monoclonal antibody linked to the toxin calicheamicin, in subjects with advanced tumors expressing the Lewis-Y antigen. The primary study objective was to determine the biodistribution and pharmacokinetics (PK) of 111-In-CMD-193 (i.e., CMD-193 tagged with a small amount of radioactive Indium [111-In]), with secondary objectives of determining changes in tumor metabolism and describing the antitumor responses to CMD-193.
Read the detailed description
Subjects received a single infusion of 111-In-CMD-193 on Day 1. Collection of blood for PK and whole body gamma camera imaging for assessment of biodistribution and tumor uptake were performed on Days 1, 2, 3 or 4, 5 or 6, and 7 or 8 following the 111-In-CMD-193 infusion. Subjects were evaluated for safety for 3 hours post-infusion on Day 1 of each cycle, with subsequent safety assessments performed on Days 8 and 15. Blood for human anti-human antibody (HAHA) response was collected pre-infusion, prior to each subsequent cycle (every 3 weeks) and at study discontinuation.
CMD-193 was administered on Day 1 of each subsequent 21-day cycle as a 60 (± 5) minute intravenous (IV) infusion at a dose of 1.0 mg/m^2 in Cohort 1 and 2.6 mg/m^2 in Cohort 2. Each subject received up to 6 cycles of CMD-193 (including the initial infusion of 111-In-CMD-193) until disease progression, unacceptable toxicity, or withdrawal of consent. Up to 6 additional cycles of CMD-193 were permitted if approved by the Sponsor in subjects who tolerated CMD-193 treatment and had evidence of response. Pretreatment medications (e.g., paracetamol, promethazine hydrochloride) were to be administered to reduce the incidence and severity of an anticipated infusion syndrome characterized by fever and chills, and less commonly hypotension.
Restaging by computed tomography (CT) scan was performed at the end of Cycles 2, 4, and 6. Assessment of tumor metabolism was performed by positron emission tomography with 18F-labeled fluorodeoxyglucose (18F-FDG-PET) prior to Cycle 1 and at the time of restaging at the end of Cycles 2 and 4.
- Conditions
- Neoplasms
- Being tested
- 111-Indium-CMD-193, CMD-193
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
111-Indium-CMD-193Drug
111-In-CMD-193 (3-7 mCi) was administered as an IV infusion over 60 (± 5) minutes.
CMD-193Drug
CMD-193 was administered as an IV infusion over 60 (± 5) minutes.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 (1.0 mg/m^2) | Experimental | Subjects received 111-In-CMD-193 on Day 1 of Cycle 1. Subjects received CMD-193 at a dose of 1.0 mg/m^2 on Day 1 of subsequent 21-day cycles. Receives: Drug: 111-Indium-CMD-193; Drug: CMD-193 |
| Cohort 2 (2.6 mg/m^2) | Experimental | Subjects received 111-In-CMD-193 on Day 1 of Cycle 1. Subjects received CMD-193 at a dose of 2.6 mg/m^2 on Day 1 of subsequent 21-day cycles. Receives: Drug: 111-Indium-CMD-193; Drug: CMD-193 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Summary of 111-In-CMD-193 Biodistribution Based on Gamma Camera Images
Biodistribution data were collected after subjects received a single infusion of 111-In-CMD-193 over 1 hour on Day 1 of Cycle 1. Gamma camera imaging with anterior and posterior whole body scans using conjugate view methodology were performed on Days 1, 2, 3 or 4, 5 or 6, and 7 or 8 following the 111-In-CMD-193 infusion. A standard was included in the field of view at each imaging time point. Single-photon emission computerized tomography (SPECT) imaging of relevant areas of disease were performed on at least one occasion following the 111-In-CMD-193 infusion. Biodistribution analysis was performed by examination of whole body and SPECT images by experienced nuclear medicine physicians.
Measured: Up to 8 days
Mean Effective Half-life of 111-In-CMD-193 Based on Gamma Camera Images
Gamma camera imaging with anterior and posterior whole body scans using conjugate view methodology were performed on Days 1, 2, 3 or 4, 5 or 6, and 7 or 8 following the 111-In-CMD-193 infusion. Whole body clearance, or biological half-time, was calculated from the whole body anterior and posterior planar images. A region of interest (ROI) was calculated to encompass the whole body, and for each ROI at each time point, the mean counts per pixel per minute was normalized to imaging time point Day 1. From this time-activity curve, an exponential clearance expression was fitted to obtain effective half-time. This was then corrected for the physical half-life of 111-In (67.45 hours) to account for physical decay to obtain the biological half-time.
Measured: Up to 8 days
Mean Serum Half-lives of 111-In-CMD-193
During Cycle 1 (111-In-CMD-193 infusion) serum samples for pharmacokinetics were collected on Days 1 (pre-infusion and 1 and 4 hours after the start of the infusion), 3, 8 and 15. Serum obtained from subjects following infusion of 111-In-CMD-193 was aliquoted and counted in a gamma scintillation counter. Duplicate standards prepared from the injected material were counted at each time point with serum samples to enable calculations to be corrected for the isotope physical decay. A 2-compartment IV bolus model with macro-parameters, no lag time and first order elimination (WNL Model 8) was fitted to individual labelled infusions for each subject using un-weighted nonlinear, least squares with WinNonLin version 5.2. T½α and T½β represent half lives of the initial and terminal phases of disposition.
Measured: Approximately 15 days (i.e., Days 1, 3, 8, and 15)
Mean Volume of Central Compartment of 111-In-CMD-193
During Cycle 1 (111-In-CMD-193 infusion) serum samples for pharmacokinetics were collected on Days 1 (pre-infusion and 1 and 4 hours after the start of the infusion), 3, 8 and 15. Serum obtained from subjects following infusion of 111-In-CMD-193 was aliquoted and counted in a gamma scintillation counter. Duplicate standards prepared from the injected material were counted at each time point with serum samples to enable calculations to be corrected for the isotope physical decay. A 2-compartment IV bolus model with macro-parameters, no lag time and first order elimination (WNL Model 8) was fitted to individual labelled infusions for each subject using un-weighted nonlinear, least squares with WinNonLin version 5.2.
Measured: Approximately 15 days (i.e., Days 1, 3, 8, and 15)
Mean Total Serum Clearance of 111-In-CMD-193
During Cycle 1 (111-In-CMD-193 infusion) serum samples for pharmacokinetics were collected on Days 1 (pre-infusion and 1 and 4 hours after the start of the infusion), 3, 8 and 15. Serum obtained from subjects following infusion of 111-In-CMD-193 was aliquoted and counted in a gamma scintillation counter. Duplicate standards prepared from the injected material were counted at each time point with serum samples to enable calculations to be corrected for the isotope physical decay. A 2-compartment IV bolus model with macro-parameters, no lag time and first order elimination (WNL Model 8) was fitted to individual labelled infusions for each subject using un-weighted nonlinear, least squares with WinNonLin version 5.2.
Measured: Approximately 15 days (i.e., Days 1, 3, 8, and 15)
Mean Area Under the Serum Concentration Curve Extrapolated to Infinite Time for 111-In-CMD-193
During Cycle 1 (111-In-CMD-193 infusion) serum samples for pharmacokinetics were collected on Days 1 (pre-infusion and 1 and 4 hours after the start of the infusion), 3, 8 and 15. Serum obtained from subjects following infusion of 111-In-CMD-193 was aliquoted and counted in a gamma scintillation counter. Duplicate standards prepared from the injected material were counted at each time point with serum samples to enable calculations to be corrected for the isotope physical decay. A 2-compartment IV bolus model with macro-parameters, no lag time and first order elimination (WNL Model 8) was fitted to individual labelled infusions for each subject using un-weighted nonlinear, least squares with WinNonLin version 5.2.
Measured: Approximately 15 days (i.e., Days 1, 3, 8, and 15)
Secondary outcomes (2)
Number of Subjects With Best Tumor Response as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST)
Computed tomography (CT) scans were performed at screening, between Days 15 and 21 of Cycles 2 and 4, and at study completion. Response was assessed using RECIST version 1.0 (Therasse et al, J Natl Cancer Inst 2000; 92:205-16), and all response assessment was performed by a single experienced radiologist. 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.
Measured: Up to 4 months
Number of Subjects With Best Metabolic Tumor Response by European Organisation for Research and Treatment of Cancer (EORTC) Guidelines at End of Study
Positron emission tomography with 18F-labeled fluorodeoxyglucose (18F-FDG-PET) was done at screening and between Days 15-21 of Cycles 2 and 4 or at study completion. Metabolic response was calculated using the target lesion with the greatest baseline standardized uptake value (SUV) and categorized per EORTC guidelines (Young et al. Eur J Cancer 1999;35:1773-82): progressive metabolic disease was an increase in 18F-FDG tumor maximum SUV (SUVmax) of > 25% within the tumor ROI determined on baseline scans, visible increase in 18F-FDG tumor uptake (>20% in the longest dimension) or new 18F-FDG uptake in metastatic lesions. Stable metabolic disease was an increase in tumor 18F-FDG SUVmax of < 25% or decrease of < 15% and no visible increase in 18F-FDG tumor uptake (>20% in the longest dimension). Partial metabolic response was a reduction of 15-25% in tumor 18F-FDG SUVmax after 1 cycle and > 25% after > 1 cycle (reduced tumor 18F-FDG uptake was not required).
Measured: Up to 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2006 (estimated)
- Study startFeb 2006
- Primary completionMay 2007
- Study completionMay 2007
Why it stopped: Abnormal distribution and lack of tumor targeting were observed.
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 (3)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ludwig Institute for Cancer Research
- Sponsor type
- University, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer
- Responsible party
- Sponsor
- Investigators
- A/Prof. Andrew M Scott, MBBS MD DDU, Principal investigator, Ludwig Institute for Cancer Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00293215
- Sponsor's protocol ID
- LUD2004-015
- Status last verified
- Oct 2022
- First submitted
- 15 Feb 2006
- Last updated
- 10 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- 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 10655437Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, Pruim J, Price P. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999 Dec;35(13):1773-82. doi: 10.1016/s0959-8049(99)00229-4.
PubMed 10673991Herbertson RA, Tebbutt NC, Lee FT, MacFarlane DJ, Chappell B, Micallef N, Lee ST, Saunder T, Hopkins W, Smyth FE, Wyld DK, Bellen J, Sonnichsen DS, Brechbiel MW, Murone C, Scott AM. Phase I biodistribution and pharmacokinetic study of Lewis Y-targeting immunoconjugate CMD-193 in patients with advanced epithelial cancers. Clin Cancer Res. 2009 Nov 1;15(21):6709-15. doi: 10.1158/1078-0432.CCR-09-0536. Epub 2009 Oct 13.
PubMed 19825951
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Biodistribution Study of 111-Indium-CMD-193 in Patients With Advanced Tumours Expressing the Lewis-Y Antigen
- ClinicalTrials.gov ID
- NCT00293215
- Acronym / sponsor ID
- LUD2004-015
- Conditions
- Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Abnormal distribution and lack of tumor targeting were observed.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Ludwig Institute for Cancer ResearchUniversity, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer
- Study start
- Feb 2006 (actual)
- Primary completion
- May 2007 (actual)
- Study completion
- May 2007 (actual)
- First posted
- 17 Feb 2006 (estimated)
- Results
- Posted 10 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a Phase 1 dose-escalation study of CMD-193, a humanized monoclonal antibody linked to the toxin calicheamicin, in subjects with advanced tumors expressing the Lewis-Y antigen. The primary study objective was to determine the biodistribution and pharmacokinetics (PK) of 111-In-CMD-193 (i.e., CMD-193 tagged with a small amount of radioactive Indium [111-In]), with secondary objectives of determining changes in tumor metabolism and describing the antitumor responses to CMD-193.
Detailed description
Subjects received a single infusion of 111-In-CMD-193 on Day 1. Collection of blood for PK and whole body gamma camera imaging for assessment of biodistribution and tumor uptake were performed on Days 1, 2, 3 or 4, 5 or 6, and 7 or 8 following the 111-In-CMD-193 infusion. Subjects were evaluated for safety for 3 hours post-infusion on Day 1 of each cycle, with subsequent safety assessments performed on Days 8 and 15. Blood for human anti-human antibody (HAHA) response was collected pre-infusion, prior to each subsequent cycle (every 3 weeks) and at study discontinuation.
CMD-193 was administered on Day 1 of each subsequent 21-day cycle as a 60 (± 5) minute intravenous (IV) infusion at a dose of 1.0 mg/m^2 in Cohort 1 and 2.6 mg/m^2 in Cohort 2. Each subject received up to 6 cycles of CMD-193 (including the initial infusion of 111-In-CMD-193) until disease progression, unacceptable toxicity, or withdrawal of consent. Up to 6 additional cycles of CMD-193 were permitted if approved by the Sponsor in subjects who tolerated CMD-193 treatment and had evidence of response. Pretreatment medications (e.g., paracetamol, promethazine hydrochloride) were to be administered to reduce the incidence and severity of an anticipated infusion syndrome characterized by fever and chills, and less commonly hypotension.
Restaging by computed tomography (CT) scan was performed at the end of Cycles 2, 4, and 6. Assessment of tumor metabolism was performed by positron emission tomography with 18F-labeled fluorodeoxyglucose (18F-FDG-PET) prior to Cycle 1 and at the time of restaging at the end of Cycles 2 and 4.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 (1.0 mg/m^2) | Experimental | Drug: 111-Indium-CMD-193, Drug: CMD-193Subjects received 111-In-CMD-193 on Day 1 of Cycle 1. Subjects received CMD-193 at a dose of 1.0 mg/m^2 on Day 1 of subsequent 21-day cycles. |
| Cohort 2 (2.6 mg/m^2) | Experimental | Drug: 111-Indium-CMD-193, Drug: CMD-193Subjects received 111-In-CMD-193 on Day 1 of Cycle 1. Subjects received CMD-193 at a dose of 2.6 mg/m^2 on Day 1 of subsequent 21-day cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Signed and dated Institutional Review Board (IRB)-approved informed consent before any protocol-specific screening procedures were performed.
- Histologically confirmed malignant solid tumor that had progressed following standard therapy, or for which no standard effective treatment was available.
- Tumor expression of Lewis-Y antigen (≥20% tumor cells positive for Lewis-Y by immunohistochemistry assay).
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST), including the presence of at least one measurable lesion at least 2 cm in size suitable for 18F-FDG PET imaging.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (7 listed)
- Chemotherapy, radiation therapy, other cancer therapy, or investigational agents within 21 days of the first dose of CMD-193 (42 days if the previous chemotherapy included nitrosoureas or mitomycin C).
- Symptomatic or clinically active central nervous system (CNS) metastases. Subjects who had prior treatment with radiotherapy or surgical resection for CNS metastases were permitted if CNS metastases had remained stable and not required any treatment for at least 3 months prior to the first dose of CMD-193.
- Significant prior allergic reaction to recombinant human or murine proteins.
- History of cirrhosis, current or chronic hepatitis B or C infections, or other significant active liver disease.
- Unstable or serious concurrent medical conditions. Examples included, but were not limited to, bleeding gastric ulcers, gastrointestinal bleeding, hepatitis, significant disorders of the immune system (eg, systemic lupus erythematosus), pancreatitis, congestive heart failure, serious active infections (e.g. requiring antibiotics or antiviral agents), unstable angina, recent myocardial infarction (within 6 months of screening), ongoing maintenance therapy for life-threatening ventricular arrhythmia, or uncontrolled major seizure disorder.
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 |
|---|---|---|
| 111-Indium-CMD-193111-In-CMD-193 (3-7 mCi) was administered as an IV infusion over 60 (± 5) minutes. | Drug | Cohort 1 (1.0 mg/m^2), Cohort 2 (2.6 mg/m^2) |
| CMD-193CMD-193 was administered as an IV infusion over 60 (± 5) minutes. | Drug | Cohort 1 (1.0 mg/m^2), Cohort 2 (2.6 mg/m^2) |
Primary outcome
Summary of 111-In-CMD-193 Biodistribution Based on Gamma Camera Images
Time frame: Up to 8 days
Biodistribution data were collected after subjects received a single infusion of 111-In-CMD-193 over 1 hour on Day 1 of Cycle 1. Gamma camera imaging with anterior and posterior whole body scans using conjugate view methodology were performed on Days 1, 2, 3 or 4, 5 or 6, and 7 or 8 following the 111-In-CMD-193 infusion. A standard was included in the field of view at each imaging time point. Single-photon emission computerized tomography (SPECT) imaging of relevant areas of disease were performed on at least one occasion following the 111-In-CMD-193 infusion. Biodistribution analysis was performed by examination of whole body and SPECT images by experienced nuclear medicine physicians.
Mean Effective Half-life of 111-In-CMD-193 Based on Gamma Camera Images
Time frame: Up to 8 days
Gamma camera imaging with anterior and posterior whole body scans using conjugate view methodology were performed on Days 1, 2, 3 or 4, 5 or 6, and 7 or 8 following the 111-In-CMD-193 infusion. Whole body clearance, or biological half-time, was calculated from the whole body anterior and posterior planar images. A region of interest (ROI) was calculated to encompass the whole body, and for each ROI at each time point, the mean counts per pixel per minute was normalized to imaging time point Day 1. From this time-activity curve, an exponential clearance expression was fitted to obtain effective half-time. This was then corrected for the physical half-life of 111-In (67.45 hours) to account for physical decay to obtain the biological half-time.
Mean Serum Half-lives of 111-In-CMD-193
Time frame: Approximately 15 days (i.e., Days 1, 3, 8, and 15)
During Cycle 1 (111-In-CMD-193 infusion) serum samples for pharmacokinetics were collected on Days 1 (pre-infusion and 1 and 4 hours after the start of the infusion), 3, 8 and 15. Serum obtained from subjects following infusion of 111-In-CMD-193 was aliquoted and counted in a gamma scintillation counter. Duplicate standards prepared from the injected material were counted at each time point with serum samples to enable calculations to be corrected for the isotope physical decay. A 2-compartment IV bolus model with macro-parameters, no lag time and first order elimination (WNL Model 8) was fitted to individual labelled infusions for each subject using un-weighted nonlinear, least squares with WinNonLin version 5.2. T½α and T½β represent half lives of the initial and terminal phases of disposition.
Mean Volume of Central Compartment of 111-In-CMD-193
Time frame: Approximately 15 days (i.e., Days 1, 3, 8, and 15)
During Cycle 1 (111-In-CMD-193 infusion) serum samples for pharmacokinetics were collected on Days 1 (pre-infusion and 1 and 4 hours after the start of the infusion), 3, 8 and 15. Serum obtained from subjects following infusion of 111-In-CMD-193 was aliquoted and counted in a gamma scintillation counter. Duplicate standards prepared from the injected material were counted at each time point with serum samples to enable calculations to be corrected for the isotope physical decay. A 2-compartment IV bolus model with macro-parameters, no lag time and first order elimination (WNL Model 8) was fitted to individual labelled infusions for each subject using un-weighted nonlinear, least squares with WinNonLin version 5.2.
Mean Total Serum Clearance of 111-In-CMD-193
Time frame: Approximately 15 days (i.e., Days 1, 3, 8, and 15)
During Cycle 1 (111-In-CMD-193 infusion) serum samples for pharmacokinetics were collected on Days 1 (pre-infusion and 1 and 4 hours after the start of the infusion), 3, 8 and 15. Serum obtained from subjects following infusion of 111-In-CMD-193 was aliquoted and counted in a gamma scintillation counter. Duplicate standards prepared from the injected material were counted at each time point with serum samples to enable calculations to be corrected for the isotope physical decay. A 2-compartment IV bolus model with macro-parameters, no lag time and first order elimination (WNL Model 8) was fitted to individual labelled infusions for each subject using un-weighted nonlinear, least squares with WinNonLin version 5.2.
Mean Area Under the Serum Concentration Curve Extrapolated to Infinite Time for 111-In-CMD-193
Time frame: Approximately 15 days (i.e., Days 1, 3, 8, and 15)
During Cycle 1 (111-In-CMD-193 infusion) serum samples for pharmacokinetics were collected on Days 1 (pre-infusion and 1 and 4 hours after the start of the infusion), 3, 8 and 15. Serum obtained from subjects following infusion of 111-In-CMD-193 was aliquoted and counted in a gamma scintillation counter. Duplicate standards prepared from the injected material were counted at each time point with serum samples to enable calculations to be corrected for the isotope physical decay. A 2-compartment IV bolus model with macro-parameters, no lag time and first order elimination (WNL Model 8) was fitted to individual labelled infusions for each subject using un-weighted nonlinear, least squares with WinNonLin version 5.2.
2 secondary outcomes
Number of Subjects With Best Tumor Response as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: Up to 4 months
Number of Subjects With Best Metabolic Tumor Response by European Organisation for Research and Treatment of Cancer (EORTC) Guidelines at End of Study
Time frame: Up to 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2022.
- 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.
- Background: PubMed 10673991Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, Pruim J, Price P. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999 Dec;35(13):1773-82. doi: 10.1016/s0959-8049(99)00229-4.
- Results publication: PubMed 19825951Herbertson RA, Tebbutt NC, Lee FT, MacFarlane DJ, Chappell B, Micallef N, Lee ST, Saunder T, Hopkins W, Smyth FE, Wyld DK, Bellen J, Sonnichsen DS, Brechbiel MW, Murone C, Scott AM. Phase I biodistribution and pharmacokinetic study of Lewis Y-targeting immunoconjugate CMD-193 in patients with advanced epithelial cancers. Clin Cancer Res. 2009 Nov 1;15(21):6709-15. doi: 10.1158/1078-0432.CCR-09-0536. Epub 2009 Oct 13.
- Individual participant dataSharing planned: No
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Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
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.
A/Prof. Andrew M Scott, MBBS MD DDU principal investigator
Ludwig Institute for Cancer Research
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 111-Indium-CMD-193 and CMD-193 in people with Neoplasms, run by Ludwig Institute for Cancer Research at 2 sites in Australia.
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 15 inclusion and 7 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: stopped early, as of the sponsor's last update on 10 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Australia. 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 10 Aug 2020). 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?
Summary of 111-In-CMD-193 Biodistribution Based on Gamma Camera Images (time frame: Up to 8 days). The study lists 6 primary outcomes in all. 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 NCT00293215, which also lists 3 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 10 Oct 2022.