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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00291447




Registration number
NCT00291447
Ethics application status
Date submitted
10/02/2006
Date registered
14/02/2006
Date last updated
10/10/2022

Titles & IDs
Public title
111In-ch806 in Patients With Advanced Tumours Expressing the 806 Antigen
Scientific title
A Phase 1 Single Dose Escalation Trial of ch806 in Patients With Advanced Tumours Expressing the 806 Antigen
Secondary ID [1] 0 0
LUD2004-001
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: Other - ch806

Experimental: Cohort 1 - Patients received a single infusion of 5 mg/m2 111In-ch806 on Day 0 and followed for 30 days post infusion.

Experimental: Cohort 2 - Patients received a single infusion of 10 mg/m2 111In-ch806 on Day 0 and followed for 30 days post infusion.

Experimental: Cohort 3 - Patients received a single infusion of 20 mg/m2 111In-ch806 on Day 0 and followed for 30 days post infusion.

Experimental: Cohort 4 - Patients received a single infusion of 40 mg/m2 111In-ch806 on Day 0 and followed for 30 days post infusion.


Treatment: Other: ch806
ch806 is a chimeric (part human, part mouse) antibody which recognizes and attaches to a protein called the 806 antigen (a type of EGFR), which is found on the surface of some cancer cells.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Patients With Adverse Events
Assessment method [1] 0 0
All AEs occurring during the study were documented on the respective case report form (CRF) pages. Events, which occurred after signed informed consent, but before first administration of study drug, were documented on the Pre-existing Signs and Symptom page. Thereafter, they were documented on the Adverse Event page. Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Documentation of AEs includes: date and time of onset and resolution, severity, frequency, seriousness, related interventions and outcome. Dose limiting toxicity (DLT) was defined as any Grade 2 or greater allergic reaction related to 111In-ch806 antibody protein, and any Grade 4 haematological or Grade 3 or greater non-haematological toxicity except for skin rash, occurring within 30 days of the 111In-ch806 infusion.
Timepoint [1] 0 0
30 days
Secondary outcome [1] 0 0
Biodistribution of 111In-ch806 Using Whole Body Clearance Methodology or Biological Halftime (T1/2-biol) Following the First Infusion.
Assessment method [1] 0 0
Gamma camera images were acquired on Day 0 (1-4 hours after 111In-ch806 infusion), and on Day 1, Day 2 or 3, Day 4 or 5, and Day 6 or 7 post 111In-ch806 infusion. Image analysis was performed by defining regions of interest (ROIs) around the kidneys, liver, spleen and lungs and whole body. T1/2-biol was calculated from the whole body anterior and posterior planar images. A ROI was calculated to encompass the whole body via a morphological dilation and erosion of a binarized planar image, at a user-defined threshold taken as a percentage (0.9 - 1.5%) of maximum pixel value of the planar image. From each ROI at each time point, the mean counts per pixel per minute was normalised to imaging time point Day 0. From this time-activity curve (TAC), an exponential clearance expression was fitted to obtain effective halftime. This was then corrected for the physical half-life of 111In (67.45 hours) to account for physical decay to obtain the biological halftime.
Timepoint [1] 0 0
Day 0 (1-4 hours after 111In-ch806 infusion), and on Day 1, Day 2 or 3, Day 4 or 5, and Day 6 or 7 post 111In-ch806 infusion.
Secondary outcome [2] 0 0
Mean Normal Organ Dosimetry of 111In-ch806 Using Normal Organ Absorbed Dose (mGy/MBq) Following the First Infusion.
Assessment method [2] 0 0
Gamma camera images were acquired on Day 0 (1-4 hours after 111In-ch806 infusion), and on Day 1, Day 2 or 3, Day 4 or 5, and Day 6 or 7 following 111In-ch806 infusion. Dosimetry analysis was performed for kidney, liver, spleen and lung. Organ radioactivity was estimated from the geometric mean (GM) of anterior and posterior sample region of interest (ROI) counts. Three regions were defined for the organs, a whole organ ROI, a sample organ ROI, and a background ROI. Average counts within sample ROIs (counts/pixel) were multiplied by the area of the organ (pixels), determined from the whole organ ROI at the time point. For paired organs,a single organ area was measured and then multiplied by two to find total area. The counts for each organ were corrected for background. A time-activity curve (TAC) was generated and fitted with a single component exponential clearance expression. The number of disintegrations, or cumulated activity, was calculated for each organ.
Timepoint [2] 0 0
Day 0 (1-4 hours after 111In-ch806 infusion), and on Day 1, Day 2 or 3, Day 4 or 5, and Day 6 or 7 following 111In-ch806 infusion.
Secondary outcome [3] 0 0
Number of Patients With Tumour Uptake of 111In-ch806 Based on Qualitative Assessment of Biodistribution Images and Dosimetry Following the First Infusion.
Assessment method [3] 0 0
Whole body gamma camera imaging with anterior and posterior whole body scans using conjugate view methodology were performed for assessment of biodistribution and tumour uptake on Day 0 (1-4 hours after 111In-ch806 infusion), Day 1, Day 2 or 3, Day 4 or 5, and Day 6 or 7 following 111In-ch806 infusion. Target lesions (\>2cm) were used to measure uptake of 111In-ch806.
Timepoint [3] 0 0
Day 0 (1-4 hours after 111In-ch806 infusion), Day 1, Day 2 or 3, Day 4 or 5, and Day 6 or 7 following 111In-ch806 infusion.
Secondary outcome [4] 0 0
Mean Half-life as Measured by Half-life of Initial Phase of Disposition (T½a) and Terminal Phase of Distribution (T½ß) of 111In-ch806 Following the First Infusion .
Assessment method [4] 0 0
The pharmacokinetics of 111In-ch806 were calculated based on gamma counting of serum samples. Serum samples for pharmacokinetics were collected on Day 0 - pre 111In-ch806 infusion; then at 5 minutes, 60 minutes, 2 hours and 4 hours post 111In-ch806 infusion, Day 1, Day 2 or 3, Day 4 or 5, Day 6 or 7, Day 14 (± 2 days) and Day 21 (± 2 days) and Day 30 (± 2 days) post infusion.
Timepoint [4] 0 0
Day 0 - pre 111In-ch806 infusion; then at 5 minutes, 60 minutes, 2 hours and 4 hours post 111In-ch806 infusion, Day 1, Day 2 or 3, Day 4 or 5, Day 6 or 7, Day 14 (± 2 days) and Day 21 (± 2 days) and Day 30 (± 2 days) post infusion.
Secondary outcome [5] 0 0
Mean Volume of the Central Compartment (V1) of 111In-ch806 Following the First Infusion.
Assessment method [5] 0 0
The pharmacokinetics of 111In-ch806 were calculated based on gamma counting of serum samples. Serum samples for pharmacokinetics were collected on Day 0 - pre 111In-ch806 infusion; then at 5 minutes, 60 minutes, 2 hours and 4 hours post 111In-ch806 infusion, Day 1, Day 2 or 3, Day 4 or 5, Day 6 or 7, Day 14 (± 2 days) and Day 21 (± 2 days) and Day 30 (± 2 days) post infusion.
Timepoint [5] 0 0
Day 0 - pre 111In-ch806 infusion; then at 5 minutes, 60 minutes, 2 hours and 4 hours post 111In-ch806 infusion, Day 1, Day 2 or 3, Day 4 or 5, Day 6 or 7, Day 14 (± 2 days) and Day 21 (± 2 days) and Day 30 (± 2 days) post infusion.
Secondary outcome [6] 0 0
Mean Total Serum Clearance (CL) of 111In-ch806 Following the First Infusion.
Assessment method [6] 0 0
The pharmacokinetics of 111In-ch806 were calculated based on gamma counting of serum samples. Serum samples for pharmacokinetics were collected on Day 0 - pre 111In-ch806 infusion; then at 5 minutes, 60 minutes, 2 hours and 4 hours post 111In-ch806 infusion, Day 1, Day 2 or 3, Day 4 or 5, Day 6 or 7, Day 14 (± 2 days) and Day 21 (± 2 days) and Day 30 (± 2 days) post infusion.
Timepoint [6] 0 0
Day 0 - pre 111In-ch806 infusion; then at 5 minutes, 60 minutes, 2 hours and 4 hours post 111In-ch806 infusion, Day 1, Day 2 or 3, Day 4 or 5, Day 6 or 7, Day 14 (± 2 days) and Day 21 (± 2 days) and Day 30 (± 2 days) post infusion.
Secondary outcome [7] 0 0
Mean Area Under the Serum Concentration Curve (AUC) of 111In-ch806 Following the First Infusion.
Assessment method [7] 0 0
The pharmacokinetics of 111In-ch806 were calculated based on gamma counting of serum samples. Serum samples for pharmacokinetics were collected on Day 0 - pre 111In-ch806 infusion; then at 5 minutes, 60 minutes, 2 hours and 4 hours post 111In-ch806 infusion, Day 1, Day 2 or 3, Day 4 or 5, Day 6 or 7, Day 14 (± 2 days) and Day 21 (± 2 days) and Day 30 (± 2 days) post infusion.
Timepoint [7] 0 0
Day 0 - pre 111In-ch806 infusion; then at 5 minutes, 60 minutes, 2 hours and 4 hours post 111In-ch806 infusion, Day 1, Day 2 or 3, Day 4 or 5, Day 6 or 7, Day 14 (± 2 days) and Day 21 (± 2 days) and Day 30 (± 2 days) post infusion.
Secondary outcome [8] 0 0
Number of Subjects With Best Overall Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)
Assessment method [8] 0 0
Tumor response was evaluated using computed tomography (CT) and categorized according to RECIST at screening (within 4 weeks of study start) and on day 30. Per RECIST, measurable lesions are categorized as follows: Complete Response (CR): complete disappearance of all target lesions; Partial Response (PR): = 30% decrease from baseline in the total measurable tumor burden (TMTB); Progressive Disease (PD): = 20% increase from nadir in TMTB; Stable Disease (SD): not meeting the above criteria.
Timepoint [8] 0 0
30 days
Secondary outcome [9] 0 0
Number of Patients With Human Anti-chimeric ch806 Antibodies (HACA)
Assessment method [9] 0 0
Patients each received a single infusion of 111In-ch806 on Day 0. To assess the secondary endpoint of immune response to ch806, patient serum samples were collected pre-infusion, then weekly until Day 30 (± 2 days) post infusion. Human antibody responses against the chimeric antibody (HACA) induced after treatment of patients were analyzed by an enzyme-linked immunosorbent assay (ELISA) technique. Patient sera was considered HACA positive if the normalized optical density (OD415) value exceeded a cut-off value of 37.10% (defined as the mean inter-patient baseline normalized OD value +3 SD of pretreatment sera).
Timepoint [9] 0 0
30 days

Eligibility
Key inclusion criteria
* Patients with advanced or metastatic tumours which are positive for 806 antigen expression based on chromogenic in situ hybridization (CISH) or immuno-histochemistry (IHC) of archived tumour samples.
* Histologically or cytologically proven malignancy.
* Measurable disease on CT scan with at least one lesion >/= 2 cm diameter (to allow adequate imaging).
* Age greater than or equal to 18 years.
* Karnofsky performance scale >/= 70.
* Within the last 2 weeks vital laboratory parameters should be within normal range, except for the following laboratory parameters, which should be within the ranges specified: Neutrophil count >/= 1.5 x 10^9/L; Platelet count >/= 150 x 10^9/L; Serum bilirubin < 34 micromol/L; Creatinine clearance > 50ml/min
* Able and willing to give valid written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Untreated active metastatic disease to the central nervous system (new or enlarging lesions on CT or MRI), or within 3 months of treatment (i.e. surgery or radiotherapy) for brain metastases. Primary central nervous system tumour (e.g. Glioblastoma Multiforme) is not an exclusion criterion.
* Other serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders.
* Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).
* Clinically significant cardiac disease (New York Heart Association Class III/IV).
* Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
* Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
* Lack of availability for immunological and clinical follow-up assessments.
* Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
* Pregnancy or breastfeeding.
* Women of childbearing potential: Refusal or inability to use effective means of contraception.
* Concomitant treatment with systemic corticosteroids except for patients with Glioblastoma. (Topical or inhalational corticosteroids are permitted.)
* Prior administration of monoclonal antibody or antibody fragment, and positive human anti-chimeric antibody (HACA) titre.

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/08/2006
Sample size
Target
Accrual to date
Final
8
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Ludwig Institute Tumor Targeting Program, Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg

Funding & Sponsors
Primary sponsor type
Other
Name
Ludwig Institute for Cancer Research
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
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
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00291447