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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
Date last updated
10/10/2022

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
The purpose of this clinical trial is to determine whether it is safe to treat patients with advanced colorectal cancer, with humanised A33 antibody tagged with radioactive iodine (131I-huA33) in combination with chemotherapy (capecitabine).
Trial website
https://clinicaltrials.gov/study/NCT00291486
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.
Herbertson RA, Tebbutt NC, Lee FT, Gill S, Chappell B, Cavicchiolo T, Saunder T, O'Keefe GJ, Poon A, Lee ST, Murphy R, Hopkins W, Scott FE, Scott AM. Targeted chemoradiation in metastatic colorectal cancer: a phase I trial of 131I-huA33 with concurrent capecitabine. J Nucl Med. 2014 Apr;55(4):534-9. doi: 10.2967/jnumed.113.132761. Epub 2014 Feb 20.
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00291486