Phase 1
Completed N=19
Capecitabine and 131I-huA33 in Patients With Metastatic Colorectal Cancer
Source: ClinicalTrials.gov NCT00291486 ↗Enrolled (actual)
19
Serious AEs
21.1%
Results posted
Jan 2022
Primary outcomePrimary: Number of Patients With Dose-Limiting Toxicities (DLT) — 0; 2; 0; 0 Participants
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Patients With Dose-Limiting Toxicities (DLT) |
0; 2; 0; 0; 0 | — |
| SECONDARY Number of Patients With Tumour Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST). |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY 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 |
219.56; 62.29; 104.89 | — |
| SECONDARY Mean Specific Absorbed Dose of 131I-huA33 for Normal Organs Calculated From the Initial Infusion |
0.12; 0.18; 0.14; 0.09; 0.056 | — |
| SECONDARY Mean Total Tumor Dose of 131I-huA33 |
13.83; 13.15; 14.89 | — |
| SECONDARY Pharmacokinetics (PK) of 131I-huA33 as Measured by T½α and T½β (Half Lives of the Initial and Terminal Phases of Disposition, Respectively) |
15.78; 28.63; 100.24; 152.60 | — |
| SECONDARY Pharmacokinetics (PK) of 131I-huA33 as Measured by Clearance (CL) |
36.72; 32.60 | 0.144 |
| SECONDARY Impact of Capecitabine on 131I-huA33 Clearance (CL) as Measured by Initial and Therapy Dose Clearance (CL) |
34.88; 40.54; 34.65; 26.88; 39.41; 35.53 | 0.361 |
| SECONDARY Pharmacokinetics (PK) of 131I-huA33 as Measured by the Volume of the Central Compartment (V1) |
3204.26; 3363.69 | — |
| SECONDARY Pharmacokinetics (PK) of 131I-huA33 as Measured by Maximum Serum Concentration (Cmax) |
1.53; 5.52 | — |
| SECONDARY Pharmacokinetics (PK) of 131I-huA33 as Measured by Area Under the Serum Concentration Curve Extrapolated to Infinite Time (AUC) |
130.43; 592.46 | — |
| SECONDARY Number of Patients With Human Anti-human Antibodies (HAHA) to 131I-huA33 |
0; 0; 0; 0; 0; 3 | — |
Eligibility Criteria
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:
- Neutrophils >/= 1.5 x 10^9/L;
- Platelets >/= 150 x 10^9/L;
- Serum bilirubin 50 ml/min.
- Age >/= 18 years.
- Able and willing to give valid written informed consent.
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.
Data sourced from ClinicalTrials.gov (NCT00291486). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.