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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00291486




Registration number
NCT00291486
Ethics application status
Date submitted
10/02/2006
Date registered
14/02/2006

Titles & IDs
Public title
Capecitabine and 131I-huA33 in Patients With Metastatic Colorectal Cancer
Scientific title
Phase I Trial of Oral Capecitabine Combined With 131I-huA33 in Patients With Metastatic Colorectal Cancer
Secondary ID [1] 0 0
R21CA108145-01A1
Secondary ID [2] 0 0
LUD2002-017
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Capecitabine
Treatment: Drugs - 131I-huA33 (131-Iodine on humanised monoclonal antibody A33)

Experimental: Cohort 1 - 20 millicurie (mCi) 131I-huA33, 1500 mg/m2/day capecitabine

All patients received an initial dose of 5 mg huA33 conjugated to 5-8 mCi 131I on day 0.

This was followed 7 ± 2 days later by inpatient administration of a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33.

Capecitabine was administered in 2 divided doses per day on days 1-14 of each 21-day cycle for a total of 4 cycles. Daily doses were rounded to the nearest 150 mg.

Experimental: Cohort 2 - 30 millicurie (mCi) 131I-huA33, 1500 mg/m2/day capecitabine

All patients received an initial dose of 5 mg huA33 conjugated to 5-8 mCi 131I on day 0.

This was followed 7 ± 2 days later by inpatient administration of a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33.

Capecitabine was administered in 2 divided doses per day on days 1-14 of each 21-day cycle for a total of 4 cycles. Daily doses were rounded to the nearest 150 mg.

Experimental: Cohort 3 - 30 millicurie (mCi) 131I-huA33, 1000 mg/m2/day capecitabine

All patients received an initial dose of 5 mg huA33 conjugated to 5-8 mCi 131I on day 0.

This was followed 7 ± 2 days later by inpatient administration of a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33.

Capecitabine was administered in 2 divided doses per day on days 1-14 of each 21-day cycle for a total of 4 cycles. Daily doses were rounded to the nearest 150 mg.

Experimental: Cohort 4 - 40 millicurie (mCi) 131I-huA33, 1000 mg/m2/day capecitabine

All patients received an initial dose of 5 mg huA33 conjugated to 5-8 mCi 131I on day 0.

This was followed 7 ± 2 days later by inpatient administration of a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33.

Capecitabine was administered in 2 divided doses per day on days 1-14 of each 21-day cycle for a total of 4 cycles. Daily doses were rounded to the nearest 150 mg.

Experimental: Cohort 5 - 40 millicurie (mCi) 131I-huA33, 1250 mg/m2/day capecitabine

All patients received an initial dose of 5 mg huA33 conjugated to 5-8 mCi 131I on day 0.

This was followed 7 ± 2 days later by inpatient administration of a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33.

Capecitabine was administered in 2 divided doses per day on days 1-14 of each 21-day cycle for a total of 4 cycles. Daily doses were rounded to the nearest 150 mg.


Treatment: Drugs: Capecitabine
Capecitabine was administered orally at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle. Daily doses were rounded to the nearest 150 mg.

Treatment: Drugs: 131I-huA33 (131-Iodine on humanised monoclonal antibody A33)
All patients received a dose of 5 mg huA33 conjugated to 5-8 mCi 131I. The therapy dose of 131I-huA33 comprised a constant protein dose of 10 mg/m2 huA33 regardless of dose level. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Patients With Dose-Limiting Toxicities (DLT)
Timepoint [1] 0 0
7 weeks
Secondary outcome [1] 0 0
Number of Patients With Tumour Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST).
Timepoint [1] 0 0
13 weeks
Secondary outcome [2] 0 0
Biodistribution of 131I-huA33 Measured by Whole Body Clearance and Normal Organ Clearance Reported as Mean Biological Half-life (T1/2 Biological) After Initial 131I-huA33 Infusion
Timepoint [2] 0 0
1 week
Secondary outcome [3] 0 0
Mean Specific Absorbed Dose of 131I-huA33 for Normal Organs Calculated From the Initial Infusion
Timepoint [3] 0 0
1 week
Secondary outcome [4] 0 0
Mean Total Tumor Dose of 131I-huA33
Timepoint [4] 0 0
5 weeks
Secondary outcome [5] 0 0
Pharmacokinetics (PK) of 131I-huA33 as Measured by T½a and T½ß (Half Lives of the Initial and Terminal Phases of Disposition, Respectively)
Timepoint [5] 0 0
5 weeks
Secondary outcome [6] 0 0
Pharmacokinetics (PK) of 131I-huA33 as Measured by Clearance (CL)
Timepoint [6] 0 0
5 weeks
Secondary outcome [7] 0 0
Impact of Capecitabine on 131I-huA33 Clearance (CL) as Measured by Initial and Therapy Dose Clearance (CL)
Timepoint [7] 0 0
5 weeks
Secondary outcome [8] 0 0
Pharmacokinetics (PK) of 131I-huA33 as Measured by the Volume of the Central Compartment (V1)
Timepoint [8] 0 0
5 weeks
Secondary outcome [9] 0 0
Pharmacokinetics (PK) of 131I-huA33 as Measured by Maximum Serum Concentration (Cmax)
Timepoint [9] 0 0
5 weeks
Secondary outcome [10] 0 0
Pharmacokinetics (PK) of 131I-huA33 as Measured by Area Under the Serum Concentration Curve Extrapolated to Infinite Time (AUC)
Timepoint [10] 0 0
5 weeks
Secondary outcome [11] 0 0
Number of Patients With Human Anti-human Antibodies (HAHA) to 131I-huA33
Timepoint [11] 0 0
13 weeks

Eligibility
Key inclusion criteria
* Metastatic colorectal cancer.
* Histologically or cytologically proven colorectal cancer.
* Measurable disease on CT scan with at least one lesion >/= 2cm diameter (to allow adequate infusion imaging).
* Expected survival of at least 4 months.
* ECOG performance status 0-2.
* Vital laboratory parameters should be within normal range including:

1. Neutrophils >/= 1.5 x 10^9/L;
2. Platelets >/= 150 x 10^9/L;
3. Serum bilirubin </= 34 micromol/L;
4. Calculated creatinine clearance > 50 ml/min.
* Age >/= 18 years.
* 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
* Previous treatment with capecitabine.
* Untreated active metastatic disease to the central nervous system (new or enlarging lesions on CT or MRI), or within 3 months of treatment (ie surgery or radiotherapy) for brain metastases.
* Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders.
* Liver involvement with metastatic disease > 50% liver volume.
* Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).
* Previous external beam irradiation except if: (i) it was for standard adjuvant pelvic radiation for rectal cancer; (ii) it was for localised irradiation for skin cancer; or (iii) the sum total of all previous external beam irradiation port areas is not greater than 25% of the total red marrow.
* Previous treatment with a monoclonal antibody or antibody fragment AND a positive huA33 human anti-human antibody (HAHA) titre.
* Concomitant treatment with systemic corticosteroids. Topical or inhalational corticosteroids are permitted.
* Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
* Lack of availability of the patient for clinical and laboratory follow-up assessment.
* 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.

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
1/10/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/08/2012
Sample size
Target
Accrual to date
Final
19
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Ludwig Institute Oncology Unit and 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
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Prof. Andrew M Scott, MBBS, DDU MD
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Herbertson RA, Tebbutt NC, Lee FT, Gill S, Chappel... [More Details]


Results are available at https://clinicaltrials.gov/study/NCT00291486