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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00293215




Registration number
NCT00293215
Ethics application status
Date submitted
15/02/2006
Date registered
17/02/2006
Date last updated
10/10/2022

Titles & IDs
Public title
Biodistribution Study of CMD-193 in Patients With Advanced Tumours Expressing the Lewis-Y Antigen
Scientific title
Phase I Biodistribution Study of 111-Indium-CMD-193 in Patients With Advanced Tumours Expressing the Lewis-Y Antigen
Secondary ID [1] 0 0
LUD2004-015
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 111-Indium-CMD-193
Treatment: Drugs - CMD-193

Experimental: Cohort 1 (1.0 mg/m^2) - 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.

Experimental: Cohort 2 (2.6 mg/m^2) - 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.


Treatment: Drugs: 111-Indium-CMD-193
111-In-CMD-193 (3-7 mCi) was administered as an IV infusion over 60 (± 5) minutes.

Treatment: Drugs: CMD-193
CMD-193 was administered as an IV infusion over 60 (± 5) minutes.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Summary of 111-In-CMD-193 Biodistribution Based on Gamma Camera Images
Timepoint [1] 0 0
Up to 8 days
Primary outcome [2] 0 0
Mean Effective Half-life of 111-In-CMD-193 Based on Gamma Camera Images
Timepoint [2] 0 0
Up to 8 days
Primary outcome [3] 0 0
Mean Serum Half-lives of 111-In-CMD-193
Timepoint [3] 0 0
Approximately 15 days (i.e., Days 1, 3, 8, and 15)
Primary outcome [4] 0 0
Mean Volume of Central Compartment of 111-In-CMD-193
Timepoint [4] 0 0
Approximately 15 days (i.e., Days 1, 3, 8, and 15)
Primary outcome [5] 0 0
Mean Total Serum Clearance of 111-In-CMD-193
Timepoint [5] 0 0
Approximately 15 days (i.e., Days 1, 3, 8, and 15)
Primary outcome [6] 0 0
Mean Area Under the Serum Concentration Curve Extrapolated to Infinite Time for 111-In-CMD-193
Timepoint [6] 0 0
Approximately 15 days (i.e., Days 1, 3, 8, and 15)
Secondary outcome [1] 0 0
Number of Subjects With Best Tumor Response as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST)
Timepoint [1] 0 0
Up to 4 months
Secondary outcome [2] 0 0
Number of Subjects With Best Metabolic Tumor Response by European Organisation for Research and Treatment of Cancer (EORTC) Guidelines at End of Study
Timepoint [2] 0 0
Up to 4 months

Eligibility
Key inclusion criteria
Inclusion criteria:

1. Signed and dated Institutional Review Board (IRB)-approved informed consent before any protocol-specific screening procedures were performed.
2. Histologically confirmed malignant solid tumor that had progressed following standard therapy, or for which no standard effective treatment was available.
3. Tumor expression of Lewis-Y antigen (=20% tumor cells positive for Lewis-Y by immunohistochemistry assay).
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Life expectancy = 18 weeks.
7. Age =18 years.
8. 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).
9. Renal test: serum creatinine = 1.5 x upper limit of normal (ULN).
10. Hepatic tests: alanine aminotransferase (ALT) levels =2.5 x ULN and total bilirubin =1.5 x ULN.
11. Pancreatic tests: amylase =1.5 x ULN and lipase = 1.5 x ULN.
12. 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).
13. 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.
14. 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.
15. Willingness of female subjects to refrain from breastfeeding infants during the study or within 28 days after the last dose of CMD-193.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

1. 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).
2. 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.
3. Significant prior allergic reaction to recombinant human or murine proteins.
4. History of cirrhosis, current or chronic hepatitis B or C infections, or other significant active liver disease.
5. 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.
6. Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
7. Any other condition that, in the Investigator's judgment, would have substantially increased the risk associated with the subject's participation in this study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2007
Sample size
Target
Accrual to date
Final
9
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Cancer Care Services, Dept. of Medical Oncology, Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [2] 0 0
Ludwig Institute Tumor Targeting Program, Austin Health - Heidelberg (Melbourne)
Recruitment postcode(s) [1] 0 0
4209 - Herston
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg (Melbourne)

Funding & Sponsors
Primary sponsor type
Other
Name
Ludwig Institute for Cancer Research
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Wyeth is now a wholly owned subsidiary of Pfizer
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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. 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.
Trial website
https://clinicaltrials.gov/study/NCT00293215
Trial related presentations / 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.
Young 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.
Herbertson 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.
Public notes

Contacts
Principal investigator
Name 0 0
A/Prof. Andrew M Scott, MBBS MD DDU
Address 0 0
Ludwig Institute for Cancer Research
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00293215