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| ID | Type | Description | Link |
|---|---|---|---|
| R21CA108145-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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).
This clinical trial tests the combination of humanised A33 monoclonal antibody tagged with radioactive iodine 131 (131I-huA33) together with capecitabine chemotherapy in patients with advanced colorectal cancer.
When colorectal cancer has spread to other organs, it is generally considered incurable but with a limited number of treatment options. Colorectal cancer cells express proteins on their surface known as antigens, and one of these is called the A33 antigen. An antibody which targets the A33 antigen was initially developed in the mouse and found to bind to human colorectal cancer cells. Because humans developed immune reactions when given the mouse antibody, an antibody, which is more like normal human antibodies, was developed (humanised A33 antibody). In order to increase its effectiveness, radioactive iodine (131I) has been attached to the antibody so that the antibody can deliver radiation directly to colorectal cancer cells. Previous studies have shown that both the unlabelled humanised A33 antibody as well as the humanised A33 antibody tagged with radioactive iodine can be administered safely to humans with no major allergic reactions. The addition of chemotherapy to radiolabelled 131I-huA33 may result in a treatment that is more effective for the treatment of colorectal cancer than either agent alone.
The purpose of this study is to determine whether it is safe to give humanised A33 antibody tagged with radioactive iodine together with chemotherapy. Different dose levels of radioactive iodine attached to a constant dose of antibody will be given together with a fixed total daily capecitabine chemotherapy dose. Providing humanised A33 antibody tagged with radioactive iodine and chemotherapy is tolerated well without major side effects, the dose of capecitabine chemotherapy given with 131I-huA33 will also be increased in order to determine the highest dose that can be given safely in combination with radio-labelled 131I-huA33. The effectiveness of the treatment combination against advanced colorectal cancer will also be assessed.
Patients with advanced colorectal cancer who have never previously received chemotherapy using capecitabine may be eligible to participate in the study. A total of between 15 and 30 patients are expected to be recruited.
Screening blood tests will be performed to determine eligibility, as well as baseline heart and lung function tests and appropriate scans to measure tumour size and assess radiation within the body. Patients will be given a trace-labelled (small radiation dose) infusion of 131I-huA33 into a vein followed a week later by the treatment infusion of 131I-huA33. The first infusion will be given as an outpatient, but for the second, patients will be hospitalized and confined to a radiation-shielded room until radiation levels fall to safe limits. Oral iodine drops will also be given for 28 days in order to protect the thyroid gland from the effects of radioactive iodine. Capecitabine chemotherapy will be taken orally and will commence at the time of the treatment infusion. Each cycle of capecitabine chemotherapy involves the medication being taken twice per day for a total of 14 days followed by 7 days rest. A total of 4 cycles of capecitabine will be given after the treatment infusion.
Blood samples will be taken just before the treatment infusion and then weekly for 13 weeks. There will be weekly physical examinations until 9 weeks after the treatment infusion and again at 12 weeks. Total study duration is 13 weeks from the trace-labelled infusion of 131I-huA33, that is 12 weeks from the treatment infusion of 131I-huA33. Patients will only receive one treatment infusion of 131I-huA33 antibody.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | 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. |
|
| Cohort 2 | Experimental | 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. |
|
| Cohort 3 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Capecitabine | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Dose-Limiting Toxicities (DLT) | Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3.0). DLT was defined as any of the following related events: Any grade 2 or greater allergic reaction related to huA33. Any grade ≥ 3 non-haematological toxicity related to 131I-huA33 or capecitabine.
Any grade ≥ 4 neutropenia ≥ 7 days in duration or any thrombocytopenia with a platelet count < 10 x 10^9/L. | 7 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Tumour Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST). | Tumor responses were evaluated using appropriate imaging and categorized according to RECIST at Screening (within 2 weeks of the first dose of study treatment), and at week 13. Per RECIST, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions; partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria (Therasse et al 2000). |
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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:
Age >/= 18 years.
Able and willing to give valid written informed consent.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Prof. Andrew M Scott, MBBS, DDU MD | Ludwig Institute for Cancer Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ludwig Institute Oncology Unit and Tumor Targeting Program, Austin Health | Heidelberg | Victoria | 3084 | Australia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10655437 | Background | 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. | |
| 24556590 | Result |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. |
| FG001 | 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. |
| FG002 | 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. |
| FG003 | 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. |
| FG004 | 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | 20 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Patients With Dose-Limiting Toxicities (DLT) | Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3.0). DLT was defined as any of the following related events: Any grade 2 or greater allergic reaction related to huA33. Any grade ≥ 3 non-haematological toxicity related to 131I-huA33 or capecitabine.
Any grade ≥ 4 neutropenia ≥ 7 days in duration or any thrombocytopenia with a platelet count < 10 x 10^9/L. | All patients who received at least one dose of study treatment. | Posted | Count of Participants | Participants | 7 weeks |
|
up to 13 weeks
Adverse Events (AEs) occurring during the study were to be documented in the source records and on the respective Case Report Form (CRF). All events, which occurred after signed informed consent but before first administration of study drug were to be documented on the Pre-existing Signs and Symptom page. Thereafter, they were to be documented on the AE page. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3.0).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 | 20 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 9.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jonathan Skipper PhD | Ludwig Institute for Cancer Research | 12124501539 | jskipper@lcr.org |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D000069287 | Capecitabine |
| ID | Term |
|---|---|
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
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| Cohort 4 | Experimental | 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. |
|
| Cohort 5 | Experimental | 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. |
|
|
| 131I-huA33 (131-Iodine on humanised monoclonal antibody A33) | Drug | 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). |
|
| 13 weeks |
| 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 | T1/2 biological is the clearance of the isotope from the whole body. Following the initial 131I-huA33 infusion, gamma camera scans were acquired over a 1 week period (1-4 hours, Day 1, Day 2 or 3, and Day 4 or 5). Whole body clearance, or biological half time, T1/2 biological, was calculated from the whole body anterior and posterior planar images. A region of interest (ROI) was calculated to encompass the whole body, and for each ROI at each time point, the mean counts per pixel per minute was normalised to imaging time point Day 1. | 1 week |
| Mean Specific Absorbed Dose of 131I-huA33 for Normal Organs Calculated From the Initial Infusion | Gamma camera imaging with anterior and posterior whole body scans using conjugate view methodology were performed on four occasions (1-4 hours, Day 1, Day 2 or 3, and Day 4 or 5) following completion of the intravenous initial infusion. Dosimetric analysis was performed on the series of gamma camera whole-body planar images acquired in all patients following the first infusion. Organ radioactivity content was estimated from the geometric mean of anterior and posterior regions of interest counts. The counts for each organ were corrected for background using regions of interest drawn adjacent to each organ where whole body thickness was comparable. | 1 week |
| Mean Total Tumor Dose of 131I-huA33 | Gamma camera imaging were performed on four occasions (1-4 hours, Day 1, Day 2 or 3, and Day 4 or 5) following completion of the initial infusion and 7+2 days post-therapy infusion in week 2, and again in week 3 or 4 and week 5 following the therapy infusion. Dosimetry analysis was performed on the series of gamma camera whole-body planar images. Tumor radioactivity content after the initial infusion was estimated from the geometric mean of anterior and posterior regions of interest counts. The counts for each organ were corrected for background using regions of interest drawn adjacent to each tumor. Resultant counts were converted to activity using a camera sensitivity factor calculated from a gamma camera standard of known activity which was scanned at the same time. | 5 weeks |
| Pharmacokinetics (PK) of 131I-huA33 as Measured by T½α and T½β (Half Lives of the Initial and Terminal Phases of Disposition, Respectively) | Blood samples for pharmacokinetics (PK) were drawn in week 0 immediately pre-initial 131I-huA33 infusion; then 5 minutes, 60 minutes and 2 hours post-initial 131I-huA33 infusion, Day 1, Day 2 or Day 3, Day 4 or Day 5. In week 1, PK samples were collected immediately pre-therapy 131I-huA33 infusion, 5 minutes, 24 ± 2 hours and approximately 7 days post-therapy 131I-huA33 infusion, then weekly until 4 weeks post therapy. Pharmacokinetic calculations were performed on serum 131I-huA33 data using a curve fitting Program (WinNonLin version 5.2; Pharsight Co., Mountain View, CA). | 5 weeks |
| Pharmacokinetics (PK) of 131I-huA33 as Measured by Clearance (CL) | Blood samples for pharmacokinetics (PK) were drawn in week 0 immediately pre-initial 131I-huA33 infusion; then 5 minutes, 60 minutes and 2 hours post-initial 131I-huA33 infusion, Day 1, Day 2 or Day 3, Day 4 or Day 5. In week 1, PK samples were collected immediately pre-therapy 131I-huA33 infusion, 5 minutes, 24 ± 2 hours and approximately 7 days post-therapy 13II-huA33 infusion, then weekly until 4 weeks post therapy. Pharmacokinetic calculations were performed on serum 131I-huA33 data using a curve fitting Program (WinNonLin version 5.2; Pharsight Co., Mountain View, CA). | 5 weeks |
| Impact of Capecitabine on 131I-huA33 Clearance (CL) as Measured by Initial and Therapy Dose Clearance (CL) | Blood samples for pharmacokinetics (PK) were drawn in week 0 immediately pre-initial 131I-huA33 infusion; then 5 minutes, 60 minutes and 2 hours post-initial 131I-huA33 infusion, Day 1, Day 2 or Day 3, Day 4 or Day 5. In week 1, PK samples were collected immediately pre-therapy 131I-huA33 infusion, 5 minutes, 24 ± 2 hours and approximately 7 days post-therapy 13II-huA33 infusion, then weekly until 4 weeks post therapy. Pharmacokinetic calculations were performed on serum 131I-huA33 data using a curve fitting Program (WinNonLin version 5.2; Pharsight Co., Mountain View, CA). | 5 weeks |
| Pharmacokinetics (PK) of 131I-huA33 as Measured by the Volume of the Central Compartment (V1) | Blood samples for pharmacokinetics (PK) were drawn in week 0 immediately pre-initial 131I-huA33 infusion; then 5 minutes, 60 minutes and 2 hours post-initial 131I-huA33 infusion, Day 1, Day 2 or Day 3, Day 4 or Day 5. In week 1, PK samples were collected immediately pre-therapy 131I-huA33 infusion, 5 minutes, 24 ± 2 hours and approximately 7 days post-therapy 131I-huA33 infusion, then weekly until 4 weeks post therapy. Pharmacokinetic calculations were performed on serum 131I-huA33 data using a curve fitting Program (WinNonLin version 5.2; Pharsight Co., Mountain View, CA). | 5 weeks |
| Pharmacokinetics (PK) of 131I-huA33 as Measured by Maximum Serum Concentration (Cmax) | Blood samples for pharmacokinetics (PK) were drawn in week 0 immediately pre-initial 131I-huA33 infusion; then 5 minutes, 60 minutes and 2 hours post-initial 131I-huA33 infusion, Day 1, Day 2 or Day 3, Day 4 or Day 5. In week 1, PK samples were collected immediately pre-therapy 131I-huA33 infusion, 5 minutes, 24 ± 2 hours and approximately 7 days post-therapy 131I-huA33 infusion, then weekly until 4 weeks post therapy. Pharmacokinetic calculations were performed on serum 131I-huA33 data using a curve fitting Program (WinNonLin version 5.2; Pharsight Co., Mountain View, CA). | 5 weeks |
| Pharmacokinetics (PK) of 131I-huA33 as Measured by Area Under the Serum Concentration Curve Extrapolated to Infinite Time (AUC) | Blood samples for pharmacokinetics (PK) were drawn in week 0 immediately pre-initial 131I-huA33 infusion; then 5 minutes, 60 minutes and 2 hours post-initial 131I-huA33 infusion, Day 1, Day 2 or Day 3, Day 4 or Day 5. In week 1, PK samples were collected immediately pre-therapy 131I-huA33 infusion, 5 minutes, 24 ± 2 hours and approximately 7 days post-therapy 131I-huA33 infusion, then weekly until 4 weeks post therapy. Pharmacokinetic calculations were performed on serum 131I-huA33 data using a curve fitting Program (WinNonLin version 5.2; Pharsight Co., Mountain View, CA). | 5 weeks |
| Number of Patients With Human Anti-human Antibodies (HAHA) to 131I-huA33 | Serum samples for human anti-human antibody (HAHA) assessment were collected prior to each 131I-huA33 infusion, at weekly intervals during weeks 0-7, then alternate weeks until the end-of-study visit. Measurement of immune responses to huA33 in patients serum was performed using a BIAcore 2000 biosensor (Biacore AB, Uppsala, Sweden). | 13 weeks |
| 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. |
| Withdrawal by Subject |
|
| Disease progression |
|
| BG001 | Cohort 2 | 30 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150mg. |
| BG002 | Cohort 3 | 30 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. |
| BG003 | Cohort 4 | 40 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. |
| BG004 | Cohort 5 | 40 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. |
| BG005 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Description |
|---|
| OG000 | Cohort 1 | 20 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. |
| OG001 | Cohort 2 | 30 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. |
| OG002 | Cohort 3 | 30 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. |
| OG003 | Cohort 4 | 40 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. |
| OG004 | Cohort 5 | 40 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. |
|
|
| Secondary | Number of Patients With Tumour Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST). | Tumor responses were evaluated using appropriate imaging and categorized according to RECIST at Screening (within 2 weeks of the first dose of study treatment), and at week 13. Per RECIST, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions; partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria (Therasse et al 2000). | All patients who received at least one dose of study treatment and were evaluable for response. One patient in Cohort 5 was not evaluable due to the patient's request to discontinue the study prior to this evaluation. | Posted | Count of Participants | Participants | 13 weeks |
|
|
|
| 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 | T1/2 biological is the clearance of the isotope from the whole body. Following the initial 131I-huA33 infusion, gamma camera scans were acquired over a 1 week period (1-4 hours, Day 1, Day 2 or 3, and Day 4 or 5). Whole body clearance, or biological half time, T1/2 biological, was calculated from the whole body anterior and posterior planar images. A region of interest (ROI) was calculated to encompass the whole body, and for each ROI at each time point, the mean counts per pixel per minute was normalised to imaging time point Day 1. | All patients who received the initial infusion of 131I-huA33. | Posted | Mean | Standard Deviation | hours | 1 week |
|
|
|
| Secondary | Mean Specific Absorbed Dose of 131I-huA33 for Normal Organs Calculated From the Initial Infusion | Gamma camera imaging with anterior and posterior whole body scans using conjugate view methodology were performed on four occasions (1-4 hours, Day 1, Day 2 or 3, and Day 4 or 5) following completion of the intravenous initial infusion. Dosimetric analysis was performed on the series of gamma camera whole-body planar images acquired in all patients following the first infusion. Organ radioactivity content was estimated from the geometric mean of anterior and posterior regions of interest counts. The counts for each organ were corrected for background using regions of interest drawn adjacent to each organ where whole body thickness was comparable. | All patients who received the initial infusion of 131I-huA33. | Posted | Mean | Standard Deviation | cGy/MBq | 1 week |
|
|
|
| Secondary | Mean Total Tumor Dose of 131I-huA33 | Gamma camera imaging were performed on four occasions (1-4 hours, Day 1, Day 2 or 3, and Day 4 or 5) following completion of the initial infusion and 7+2 days post-therapy infusion in week 2, and again in week 3 or 4 and week 5 following the therapy infusion. Dosimetry analysis was performed on the series of gamma camera whole-body planar images. Tumor radioactivity content after the initial infusion was estimated from the geometric mean of anterior and posterior regions of interest counts. The counts for each organ were corrected for background using regions of interest drawn adjacent to each tumor. Resultant counts were converted to activity using a camera sensitivity factor calculated from a gamma camera standard of known activity which was scanned at the same time. | All patients who received the initial and therapy infusions and had tumors of sufficient size for accurate tumor quantitation and dosimetry. Nine patients had tumors too small to be analyzed. Results are presented by the radiolabeled dose of huA33 given as well as all patients. | Posted | Mean | Standard Deviation | Gy | 5 weeks |
|
|
|
| Secondary | Pharmacokinetics (PK) of 131I-huA33 as Measured by T½α and T½β (Half Lives of the Initial and Terminal Phases of Disposition, Respectively) | Blood samples for pharmacokinetics (PK) were drawn in week 0 immediately pre-initial 131I-huA33 infusion; then 5 minutes, 60 minutes and 2 hours post-initial 131I-huA33 infusion, Day 1, Day 2 or Day 3, Day 4 or Day 5. In week 1, PK samples were collected immediately pre-therapy 131I-huA33 infusion, 5 minutes, 24 ± 2 hours and approximately 7 days post-therapy 131I-huA33 infusion, then weekly until 4 weeks post therapy. Pharmacokinetic calculations were performed on serum 131I-huA33 data using a curve fitting Program (WinNonLin version 5.2; Pharsight Co., Mountain View, CA). | In all cohorts, both doses of huA33 were the same. The amount of radioactivity administered does not impact the PK of the protein. The results are presented for all patients who received study therapy and had PK samples taken. Two patients were not included in the determination of mean parameter values due to curve fit instability (one after initial infusion and one after therapy infusion) and one due to a positive human anti-human antibody (HAHA) response in Week 1 (therapy infusion). | Posted | Mean | Standard Deviation | hours | 5 weeks |
|
|
|
| Secondary | Pharmacokinetics (PK) of 131I-huA33 as Measured by Clearance (CL) | Blood samples for pharmacokinetics (PK) were drawn in week 0 immediately pre-initial 131I-huA33 infusion; then 5 minutes, 60 minutes and 2 hours post-initial 131I-huA33 infusion, Day 1, Day 2 or Day 3, Day 4 or Day 5. In week 1, PK samples were collected immediately pre-therapy 131I-huA33 infusion, 5 minutes, 24 ± 2 hours and approximately 7 days post-therapy 13II-huA33 infusion, then weekly until 4 weeks post therapy. Pharmacokinetic calculations were performed on serum 131I-huA33 data using a curve fitting Program (WinNonLin version 5.2; Pharsight Co., Mountain View, CA). | In all cohorts, the doses of huA33 were the same. The amount of radioactivity administered does not impact the PK of the protein. The results are presented for all patients who received study therapy and had PK samples taken. The results excluded the following patients due to curve fit instability; 1 after the initial infusion, and 1 after the therapy infusion. Another was excluded from the results measured after the therapy infusion due to a positive human anti-human antibody (HAHA) in Week 1. | Posted | Mean | Standard Deviation | mL/hr | 5 weeks |
|
|
|
|
| Secondary | Impact of Capecitabine on 131I-huA33 Clearance (CL) as Measured by Initial and Therapy Dose Clearance (CL) | Blood samples for pharmacokinetics (PK) were drawn in week 0 immediately pre-initial 131I-huA33 infusion; then 5 minutes, 60 minutes and 2 hours post-initial 131I-huA33 infusion, Day 1, Day 2 or Day 3, Day 4 or Day 5. In week 1, PK samples were collected immediately pre-therapy 131I-huA33 infusion, 5 minutes, 24 ± 2 hours and approximately 7 days post-therapy 13II-huA33 infusion, then weekly until 4 weeks post therapy. Pharmacokinetic calculations were performed on serum 131I-huA33 data using a curve fitting Program (WinNonLin version 5.2; Pharsight Co., Mountain View, CA). | CL is a key parameter to assess the impact of capecitabine on huA33 therapy. The doses of huA33 were the same, results are presented by capecitabine dose level in patients who received study therapy and had PK samples taken. The results excluded the following patients due to curve fit instability; 1 after the initial infusion, and 1 after the therapy infusion. Another was excluded from the results measured after the therapy infusion due to a positive human anti-human antibody (HAHA) in Week 1. | Posted | Mean | Standard Deviation | ml/hr | 5 weeks |
|
|
|
|
| Secondary | Pharmacokinetics (PK) of 131I-huA33 as Measured by the Volume of the Central Compartment (V1) | Blood samples for pharmacokinetics (PK) were drawn in week 0 immediately pre-initial 131I-huA33 infusion; then 5 minutes, 60 minutes and 2 hours post-initial 131I-huA33 infusion, Day 1, Day 2 or Day 3, Day 4 or Day 5. In week 1, PK samples were collected immediately pre-therapy 131I-huA33 infusion, 5 minutes, 24 ± 2 hours and approximately 7 days post-therapy 131I-huA33 infusion, then weekly until 4 weeks post therapy. Pharmacokinetic calculations were performed on serum 131I-huA33 data using a curve fitting Program (WinNonLin version 5.2; Pharsight Co., Mountain View, CA). | In all cohorts, both doses of huA33 were the same. The amount of radioactivity administered does not impact the PK of the protein. The results excluded the following patients due to curve fit instability; 1 after the initial infusion, and 1 after the therapy infusion. Another was excluded from the results measured after the therapy infusion due to a positive human anti-human antibody (HAHA) in Week 1. | Posted | Mean | Standard Deviation | mL | 5 weeks |
|
|
|
| Secondary | Pharmacokinetics (PK) of 131I-huA33 as Measured by Maximum Serum Concentration (Cmax) | Blood samples for pharmacokinetics (PK) were drawn in week 0 immediately pre-initial 131I-huA33 infusion; then 5 minutes, 60 minutes and 2 hours post-initial 131I-huA33 infusion, Day 1, Day 2 or Day 3, Day 4 or Day 5. In week 1, PK samples were collected immediately pre-therapy 131I-huA33 infusion, 5 minutes, 24 ± 2 hours and approximately 7 days post-therapy 131I-huA33 infusion, then weekly until 4 weeks post therapy. Pharmacokinetic calculations were performed on serum 131I-huA33 data using a curve fitting Program (WinNonLin version 5.2; Pharsight Co., Mountain View, CA). | In all cohorts, both doses of huA33 were the same. The amount of radioactivity administered does not impact the PK of the protein. The results excluded the following patients due to curve fit instability; 1 after the initial infusion, and 1 after the therapy infusion. Another was excluded from the results measured after the therapy infusion due to a positive human anti-human antibody (HAHA) in Week 1. | Posted | Mean | Standard Deviation | mcg/mL | 5 weeks |
|
|
|
| Secondary | Pharmacokinetics (PK) of 131I-huA33 as Measured by Area Under the Serum Concentration Curve Extrapolated to Infinite Time (AUC) | Blood samples for pharmacokinetics (PK) were drawn in week 0 immediately pre-initial 131I-huA33 infusion; then 5 minutes, 60 minutes and 2 hours post-initial 131I-huA33 infusion, Day 1, Day 2 or Day 3, Day 4 or Day 5. In week 1, PK samples were collected immediately pre-therapy 131I-huA33 infusion, 5 minutes, 24 ± 2 hours and approximately 7 days post-therapy 131I-huA33 infusion, then weekly until 4 weeks post therapy. Pharmacokinetic calculations were performed on serum 131I-huA33 data using a curve fitting Program (WinNonLin version 5.2; Pharsight Co., Mountain View, CA). | In all cohorts, both doses of huA33 were the same. The amount of radioactivity administered does not impact the PK of the protein. The results excluded the following patients due to curve fit instability; 1 after the initial infusion, and 1 after the therapy infusion. Another was excluded from the results measured after the therapy infusion due to a positive human anti-human antibody (HAHA) in Week 1. | Posted | Mean | Standard Deviation | mcg.hr/mL | 5 weeks |
|
|
|
| Secondary | Number of Patients With Human Anti-human Antibodies (HAHA) to 131I-huA33 | Serum samples for human anti-human antibody (HAHA) assessment were collected prior to each 131I-huA33 infusion, at weekly intervals during weeks 0-7, then alternate weeks until the end-of-study visit. Measurement of immune responses to huA33 in patients serum was performed using a BIAcore 2000 biosensor (Biacore AB, Uppsala, Sweden). | All patients who received at least one dose of study therapy and had HAHA measured at the respective timepoint. | Posted | Count of Participants | Participants | 13 weeks |
|
|
|
| 0 |
| 3 |
| 0 |
| 3 |
| 3 |
| 3 |
| EG001 | Cohort 2 | 30 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. | 0 | 6 | 3 | 6 | 6 | 6 |
| EG002 | Cohort 3 | 30 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. | 0 | 3 | 0 | 3 | 3 | 3 |
| EG003 | Cohort 4 | 40 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. | 0 | 3 | 1 | 3 | 3 | 3 |
| EG004 | Cohort 5 | 40 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 the therapy dose given as a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I). Capecitabine was administered at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle for 4 cycles. Daily doses were rounded to the nearest 150 mg. | 0 | 4 | 0 | 4 | 4 | 4 |
| Febrile Neutropenia | Blood and lymphatic system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Angina | Cardiac disorders | MedDRA 9.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Non-Hodgkin's Lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 9.0 | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Monocytosis | Blood and lymphatic system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Anemia | Blood and lymphatic system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 9.0 | Systematic Assessment |
|
| Retrosternal chest pain | Cardiac disorders | MedDRA 9.0 | Systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | MedDRA 9.0 | Systematic Assessment |
|
| Hypoglycemia | Endocrine disorders | MedDRA 9.0 | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA 9.0 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Abdominal distention | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Anal discomfort | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Cheilitis | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Dysgeusia | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Epigastric discomfort | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Gastroesophageal reflux disease | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Lip dry | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Lip ulceration | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Rectal hemorrhage | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 9.0 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 9.0 | Systematic Assessment |
|
| Edema Peripheral | General disorders | MedDRA 9.0 | Systematic Assessment |
|
| Hot flush | General disorders | MedDRA 9.0 | Systematic Assessment |
|
| Lethargy | General disorders | MedDRA 9.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 9.0 | Systematic Assessment |
|
| Hyperbilirubinemia | Hepatobiliary disorders | MedDRA 9.0 | Systematic Assessment |
|
| Herpes simplex | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
|
| Animal bite | Injury, poisoning and procedural complications | MedDRA 9.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 9.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 9.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 9.0 | Systematic Assessment |
|
| Blood thyroid stimulating hormone decreased | Investigations | MedDRA 9.0 | Systematic Assessment |
|
| Gamma-glutamyl transferase increased | Investigations | MedDRA 9.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 9.0 | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | MedDRA 9.0 | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | MedDRA 9.0 | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | MedDRA 9.0 | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | MedDRA 9.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Buttock pain | Musculoskeletal and connective tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Myopathy steroid | Injury, poisoning and procedural complications | MedDRA 9.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Shoulder pain | Musculoskeletal and connective tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Sensation of heaviness | Musculoskeletal and connective tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Upper back pain | Musculoskeletal and connective tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Extrapyramidal disorder | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Hypoesthesia | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Insomnia | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Nerve root compression | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Neuropathy | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Anosmia | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Paresthesia | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Peroneal nerve palsy | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Post herpetic neuralgia | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Weakness in extremity | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA 9.0 | Systematic Assessment |
|
| Depressed mood | Psychiatric disorders | MedDRA 9.0 | Systematic Assessment |
|
| Mood altered | Psychiatric disorders | MedDRA 9.0 | Systematic Assessment |
|
| Blood urea decreased | Renal and urinary disorders | MedDRA 9.0 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 9.0 | Systematic Assessment |
|
| Renal colic | Renal and urinary disorders | MedDRA 9.0 | Systematic Assessment |
|
| Vaginal pain | Reproductive system and breast disorders | MedDRA 9.0 | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | MedDRA 9.0 | Systematic Assessment |
|
| Testicular pain | Reproductive system and breast disorders | MedDRA 9.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Pharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Rhinorrhea | Respiratory, thoracic and mediastinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Upper respiratory tract infection NOS | Respiratory, thoracic and mediastinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Contusion | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Itchy skin | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 9.0 | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA 9.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| PR |
|
| SD |
|
| PD |
|
|
| Title | Measurements |
|---|---|
|
| Lung |
|
| Red Marrow |
|
|
| T½β after initial 131I-huA33 infusion |
|
|
| T½β after therapy 131I-huA33 infusion |
|
|
|
| Therapy dose CL |
|
|
|
|
|
|
| Week 1 |
|
|
| Week 2 |
|
|
| Week 3 |
|
|
| Week 4 |
|
|
| Week 5 |
|
|
| Week 6 |
|
|
| Week 8 |
|
|
| Week 10-11 |
|
|
| Week 12-13 |
|
|
| Negative HAHA |
|
| Negative HAHA |
|
| Negative HAHA |
|
| Negative HAHA |
|
| Negative HAHA |
|
| Negative HAHA |
|
| Negative HAHA |
|
| Negative HAHA |
|
| Negative HAHA |
|