A Study of Xeloda (Capecitabine) Plus Radiation Therapy in Children With Newly Diagnosed Gliomas
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT00532948
Collaborator
(none)
24
9
1
41
2.7
0.1
Study Details
Study Description
Brief Summary
This single arm study will assess the maximum tolerated dose, and dose-limiting toxicities, of Xeloda administered concurrently with radiation therapy, in children with newly diagnosed diffuse intrinsic brain stem gliomas and high grade gliomas. Xeloda will be administered twice daily, at a starting dose of 500mg/m2 bid, beginning within 24 hours of the start of radiation therapy. Subsequent dose escalations will be in increments of 30%, using a standard dose escalation schema. Post-radiation therapy with Xeloda will continue after a 2 week break. The anticipated time on study treatment is 3-12 months, and the target sample size will not exceed 30 evaluable patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
24 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Trial of Capecitabine Rapidly Disintegrating Tablets and Concomitant Radiation Therapy in Children With Newly Diagnosed Brainstem Gliomas and High Grade Gliomas
Study Start Date
:
May 1, 2007
Actual Primary Completion Date
:
Oct 1, 2010
Actual Study Completion Date
:
Oct 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1
|
Drug: capecitabine [Xeloda]
500mg/m2 po bid (starting dose)
|
Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose (MTD) of Capecitabine. [Upto 11 weeks.]
The MTD was the dose level at which six evaluable patients had been treated and at most one patient experienced a dose limiting toxicity (DLT) and the next highest dose level was too toxic. Dose escalation occurred if 0 out of 3 or at most 1 out of 6 patients experienced DLT while being treated at a dose level; otherwise the dose was declared unsafe and thus above the MTD.
- Dose Limiting Toxicities (DLTs) [Upto 11 weeks]
DLT was defined as any of the following events occurring during the 11 week dose-finding period: any event that leads to interruption of planned radiation for 5 consecutive days or 10 days total; Grade 4 neutropenia or thrombocytopenia; Grade 3 thrombocytopenia that required a platelet transfusion on 2 or more occasions; any Grade 3 or 4 non-hematologic toxicity (with the exception of grade 3 nausea or vomiting of less than 5 days duration, Grade 3 transaminases that returned to baseline value within 7 days of study drug interruption and that did not recur upon re-challenge with study drug, and/or Grade 3 fever or infection of <5 days duration); Grade 2 non-hematologic toxicities that persisted for >7 days and required treatment interruption, or any other capecitabine-related adverse events that required need for dose reduction or permanent cessation of therapy, interruption of study drug for >7 days or recurred on re-challenge with capecitabine rapidly disintegrating tablets (RDTs).
- Number of Participants With Adverse Events (AE) [Up to 06 years]
An AE is an unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Toxicity was monitored and graded according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Adverse events that were not included in the CTCAEv3.0 were reported and graded under the other AE within the appropriate category.
- Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters [Up to 06 years]
For hematology, the parameters assessed were: Hemoglobin, hematocrit, platelet count, RBC, WBC, lymphocytes, monocytes,granulocytes (blasts), neutrophils(segs, bands),eosinophils and basophils.
- Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters [Up to 06 years]
For blood chemistry, the parameters assessed were: Sodium, potassium, calcium, magnesium, chloride, bicarbonate, total protein, albumin, alkaline phosphatase, alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), Lactate dehydrogenase (LDH), total bilirubin, direct bilirubin, indirect bilirubin, creatinine (serum creatinine or creatinine clearance), glucose.
Secondary Outcome Measures
- Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) [Day 1 and Day 14]
The maximum observed plasma concentration of capecitabine and its metabolites. Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline [pre-dose], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline [pre-dose], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing).
- Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) [Day 1 and Day 14]
Tmax is the corresponding time at which Cmax occurs of capecitabine and its metabolites.Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline [pre-dose], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline [pre-dose], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing).
- The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) [Day 1 and Day 14]
AUC last concentration of capecitabine and its metabolites. Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline [pre-dose], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline [pre-dose], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing).
- Anti Tumor Activity [Up to 6 years]
Tumor response refers to the best response prior to failure (disease progression, death or second malignancy).
Eligibility Criteria
Criteria
Ages Eligible for Study:
3 Years
to 21 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
patients >=3 and <=21 years of age;
-
newly diagnosed non-disseminated brainstem glioma or non-disseminated high grade glioma;
-
Karnofsky (if >16 years) or Lansky (if < 16 years) Performance Scale of >=50%;
-
adequate organ function.
Exclusion Criteria:
-
previous chemotherapy, radiation therapy, immunotherapy or bone marrow transplant;
-
uncontrolled infection;
-
known DPD deficiency.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | San Francisco | California | United States | 94143-0780 | |
| 2 | Washington | District of Columbia | United States | 20010 | |
| 3 | Chicago | Illinois | United States | 60614 | |
| 4 | Boston | Massachusetts | United States | 02115-6084 | |
| 5 | Durham | North Carolina | United States | 27710 | |
| 6 | Philadelphia | Pennsylvania | United States | 19104 | |
| 7 | Pittsburgh | Pennsylvania | United States | 15261 | |
| 8 | Houston | Texas | United States | 77030 | |
| 9 | Seattle | Washington | United States | 98105 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Chair: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00532948
Other Study ID Numbers:
- NO18517
First Posted:
Sep 21, 2007
Last Update Posted:
Dec 7, 2016
Last Verified:
Oct 1, 2016
Study Results
Participant Flow
| Recruitment Details | All participants in the study were enrolled at Pediatric Brain Tumor Consortium (PBTC) institutions in the United States of America (USA), from 24 May 2007 through 27 October 2009. |
|---|---|
| Pre-assignment Detail | The study consisted of two periods of dosing: A dose-finding treatment period of 11 weeks and a post radiation treatment phase that lasted for 9 weeks. |
| Arm/Group Title | Capecitabine 500 mg/m^2 | Capecitabine 650 mg/m^2 | Capecitabine 850 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Capecitabine 500 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy. | Capecitabine 650 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy. | Capecitabine 850 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy. |
| Period Title: Overall Study | |||
| STARTED | 4 | 14 | 6 |
| COMPLETED | 0 | 9 | 2 |
| NOT COMPLETED | 4 | 5 | 4 |
Baseline Characteristics
| Arm/Group Title | Capecitabine 500 mg/m^2 | Capecitabine 650 mg/m^2 | Capecitabine 850 mg/m^2 | Total |
|---|---|---|---|---|
| Arm/Group Description | Capecitabine 500 mg/m^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy. | Capecitabine 650 mg/m^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy. | Capecitabine 850 mg/m^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy. | Total of all reporting groups |
| Overall Participants | 4 | 14 | 6 | 24 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
7.5
(1.73)
|
8.4
(2.65)
|
13
(3.41)
|
9.37
(3.39)
|
| Gender (Count of Participants) | ||||
| Female |
1
25%
|
12
85.7%
|
2
33.3%
|
15
62.5%
|
| Male |
3
75%
|
2
14.3%
|
4
66.7%
|
9
37.5%
|
Outcome Measures
| Title | Maximum Tolerated Dose (MTD) of Capecitabine. |
|---|---|
| Description | The MTD was the dose level at which six evaluable patients had been treated and at most one patient experienced a dose limiting toxicity (DLT) and the next highest dose level was too toxic. Dose escalation occurred if 0 out of 3 or at most 1 out of 6 patients experienced DLT while being treated at a dose level; otherwise the dose was declared unsafe and thus above the MTD. |
| Time Frame | Upto 11 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population consisted of all eligible patients who received at least one dose of capecitabine. |
| Arm/Group Title | Capecitabine (Overall) |
|---|---|
| Arm/Group Description | Capecitabine 500, 650, and 850 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy |
| Measure Participants | 22 |
| Number [milligrams] |
650
|
| Title | Dose Limiting Toxicities (DLTs) |
|---|---|
| Description | DLT was defined as any of the following events occurring during the 11 week dose-finding period: any event that leads to interruption of planned radiation for 5 consecutive days or 10 days total; Grade 4 neutropenia or thrombocytopenia; Grade 3 thrombocytopenia that required a platelet transfusion on 2 or more occasions; any Grade 3 or 4 non-hematologic toxicity (with the exception of grade 3 nausea or vomiting of less than 5 days duration, Grade 3 transaminases that returned to baseline value within 7 days of study drug interruption and that did not recur upon re-challenge with study drug, and/or Grade 3 fever or infection of <5 days duration); Grade 2 non-hematologic toxicities that persisted for >7 days and required treatment interruption, or any other capecitabine-related adverse events that required need for dose reduction or permanent cessation of therapy, interruption of study drug for >7 days or recurred on re-challenge with capecitabine rapidly disintegrating tablets (RDTs). |
| Time Frame | Upto 11 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population consisted of all eligible patients who received at least one dose of capecitabine. |
| Arm/Group Title | Capecitabine 500 mg/m^2 | Capecitabine 650 mg/m^2 | Capecitabine 850 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Capecitabine 500 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 650 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 850 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy |
| Measure Participants | 4 | 12 | 6 |
| Number [Participants] |
0
0%
|
3
21.4%
|
3
50%
|
| Title | Number of Participants With Adverse Events (AE) |
|---|---|
| Description | An AE is an unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Toxicity was monitored and graded according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Adverse events that were not included in the CTCAEv3.0 were reported and graded under the other AE within the appropriate category. |
| Time Frame | Up to 06 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population consisted of all eligible patients who received at least one dose of capecitabine. |
| Arm/Group Title | Capecitabine 500 mg/m^2 | Capecitabine 650 mg/m^2 | Capecitabine 850 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Capecitabine 500 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 650 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 850 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy |
| Measure Participants | 4 | 12 | 6 |
| Number [Participants] |
3
75%
|
12
85.7%
|
6
100%
|
| Title | Number of Participants With Baseline Shift From Normal to Low or High in Hematology Parameters |
|---|---|
| Description | For hematology, the parameters assessed were: Hemoglobin, hematocrit, platelet count, RBC, WBC, lymphocytes, monocytes,granulocytes (blasts), neutrophils(segs, bands),eosinophils and basophils. |
| Time Frame | Up to 06 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population consisted of all eligible patients who received at least one dose of capecitabine. Participants available at a particular time point were included in analysis. |
| Arm/Group Title | Capecitabine 500 mg/m^2 | Capecitabine 650 mg/m^2 | Capecitabine 850 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Capecitabine 500 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 650 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 850 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy |
| Measure Participants | 4 | 12 | 6 |
| Haematocrit, normal to low, n=3,1,5 |
2
50%
|
1
7.1%
|
4
66.7%
|
| Haematocrit, normal to high, n=3,1,5 |
0
0%
|
0
0%
|
0
0%
|
| Hemoglobin, normal to low, n=4,2,6 |
0
0%
|
0
0%
|
2
33.3%
|
| Hemoglobin, normal to high, n=4,2,6 |
0
0%
|
0
0%
|
0
0%
|
| White blood cell, normal to low, n=3,1,5 |
0
0%
|
0
0%
|
0
0%
|
| White blood cell, normal to high, n=3,1,5 |
1
25%
|
1
7.1%
|
1
16.7%
|
| Platelets, normal to low, n=4,2,6 |
0
0%
|
1
7.1%
|
0
0%
|
| Platelets, normal to high, n=4,2,6 |
0
0%
|
0
0%
|
1
16.7%
|
| Red blood cells, normal to low, n=3,1,3 |
2
50%
|
0
0%
|
1
16.7%
|
| Red blood cells, normal to high, n=3,1,3 |
0
0%
|
1
7.1%
|
0
0%
|
| Neutrophils (segmented), normal to low , n=3,0,5 |
0
0%
|
0
0%
|
0
0%
|
| Neutrophils (segmented), normal to high, n=3,0,5 |
0
0%
|
0
0%
|
0
0%
|
| Basophils (relative), normal to low, n=0,1,2 |
0
0%
|
0
0%
|
0
0%
|
| Basophils (relative), normal to high, n=0,1,2 |
0
0%
|
1
7.1%
|
2
33.3%
|
| Lymphocytes (relative), normal to low, n=3,1,5 |
0
0%
|
0
0%
|
0
0%
|
| Lymphocytes (relative), normal to high, n=3,1,5 |
0
0%
|
0
0%
|
0
0%
|
| Monocytes (relative), normal to low, n=3,1,4 |
0
0%
|
0
0%
|
0
0%
|
| Monocytes (relative), normal to high, n=3,1,4 |
1
25%
|
0
0%
|
3
50%
|
| Eosinophils (relative), normal to low, n=1,1,3 |
0
0%
|
1
7.1%
|
0
0%
|
| Eosinophils (relative), normal to high, n=1,1,3 |
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Baseline Shift From Normal to Low or High in Blood Chemistry Parameters |
|---|---|
| Description | For blood chemistry, the parameters assessed were: Sodium, potassium, calcium, magnesium, chloride, bicarbonate, total protein, albumin, alkaline phosphatase, alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), Lactate dehydrogenase (LDH), total bilirubin, direct bilirubin, indirect bilirubin, creatinine (serum creatinine or creatinine clearance), glucose. |
| Time Frame | Up to 06 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population consisted of all eligible patients who received at least one dose of capecitabine. Participants available at a particular time point were included in analysis. |
| Arm/Group Title | Capecitabine 500 mg/m^2 | Capecitabine 650 mg/m^2 | Capecitabine 850 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Capecitabine 500 mg/m^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 650 mg/m^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 850 mg/m^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy |
| Measure Participants | 4 | 12 | 6 |
| Lactic dehydrogenase, normal to low, n=0,0,0 |
0
0%
|
0
0%
|
0
0%
|
| Lactic dehydrogenase, normal to high, n=0,0,0 |
0
0%
|
0
0%
|
0
0%
|
| Indirect bilirubin, normal to low, n=1,1,1 |
0
0%
|
0
0%
|
0
0%
|
| Indirect bilirubin, normal to high, n=1,1,1 |
0
0%
|
1
7.1%
|
0
0%
|
| BUN, normal to low, n=3,1,5 |
0
0%
|
0
0%
|
2
33.3%
|
| BUN, normal to high, n=3,1,5 |
0
0%
|
1
7.1%
|
1
16.7%
|
| Alkaline phosphatase, normal to low, n=1,1,4 |
0
0%
|
0
0%
|
1
16.7%
|
| Alkaline phosphatase, normal to high, n=1,1,4 |
0
0%
|
0
0%
|
0
0%
|
| Direct blirubin, normal to low, n=2,1,1 |
0
0%
|
0
0%
|
0
0%
|
| Direct bilirubin, normal to high, n=2,1,1 |
0
0%
|
0
0%
|
0
0%
|
| Total bilirubin, normal to low, n=4,2,6 |
0
0%
|
0
0%
|
0
0%
|
| Total bilirubin, normal to high, n=4,2,6 |
0
0%
|
0
0%
|
0
0%
|
| Fasting glucose, normal to low, n=1,0,4 |
0
0%
|
0
0%
|
0
0%
|
| Fasting glucose, normal to high, n=1,0,4 |
0
0%
|
0
0%
|
0
0%
|
| Protein, normal to low, n=1,0,2 |
1
25%
|
0
0%
|
1
16.7%
|
| Protein, normal to high, n=1,0,2 |
0
0%
|
0
0%
|
0
0%
|
| Serum albumin, normal to low, n=3,1,5 |
2
50%
|
0
0%
|
1
16.7%
|
| Serum albumin, normal to high, n=3,1,5 |
0
0%
|
0
0%
|
0
0%
|
| Serum creatinine, normal to low, n=4,2,6 |
0
0%
|
0
0%
|
0
0%
|
| Serum creatinine, normal to high, n=4,2,6 |
0
0%
|
0
0%
|
2
33.3%
|
| ASAT (SGOT), normal to low, n=1,0,4 |
0
0%
|
0
0%
|
0
0%
|
| ASAT (SGOT), normal to high, n=1,0,4 |
0
0%
|
0
0%
|
2
33.3%
|
| ALAT (SGPT), normal to low, n=4,2,6 |
0
0%
|
0
0%
|
0
0%
|
| ALAT (SGPT), normal to high, n=4,2,6 |
2
50%
|
2
14.3%
|
4
66.7%
|
| Calcium, normal to low, n=3, 1,5 |
1
25%
|
1
7.1%
|
0
0%
|
| Calcium, normal to high, n=3,1,5 |
0
0%
|
0
0%
|
1
16.7%
|
| Phosphate, normal to low, n=3,1,5 |
1
25%
|
0
0%
|
1
16.7%
|
| Phosphate, normal to high, n=3,1,5 |
0
0%
|
0
0%
|
1
16.7%
|
| Potassium, normal to low, n=3, 1,5 |
2
50%
|
0
0%
|
0
0%
|
| Potassium, normal to high, n=3,1,5 |
0
0%
|
1
7.1%
|
0
0%
|
| Sodium, normal to low, n=3,1,5 |
1
25%
|
1
7.1%
|
3
50%
|
| Sodium, normal to high, n=3,1,5 |
0
0%
|
0
0%
|
0
0%
|
| Magnesium, normal to low, n=3,1,5 |
0
0%
|
0
0%
|
0
0%
|
| Magnesium, normal to high, n=3,1,5 |
1
25%
|
1
7.1%
|
0
0%
|
| Chloride, normal to low, n=3,1,5 |
0
0%
|
0
0%
|
1
16.7%
|
| Chloride, normal to high, n=3,1,5 |
0
0%
|
1
7.1%
|
1
16.7%
|
| Bicarbonate, normal to low, n=3,0,5 |
0
0%
|
0
0%
|
0
0%
|
| Bicarbonate, normal to high, n=3,0,5 |
0
0%
|
0
0%
|
3
50%
|
| Title | Maximum Observed Plasma Concentration (Cmax) of Capecitabine and Its Metabolites (5'-Deoxy-5-Fluorocytidine [5'-DFCR], 5'-Deoxy-5-Fluorouridine [5'-DFUR], 5-Fluorouracil [5-FU] and Alpha-fluoro-beta-alanine [FBAL]) |
|---|---|
| Description | The maximum observed plasma concentration of capecitabine and its metabolites. Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline [pre-dose], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline [pre-dose], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing). |
| Time Frame | Day 1 and Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population consisted of all eligible patients who received at least one dose of capecitabine. Participants available at a particular time point were included in analysis. |
| Arm/Group Title | Capecitabine 500 mg/m^2 | Capecitabine 650 mg/m^2 | Capecitabine 850 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Capecitabine 500 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 650 mg/m^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 850 mg/m^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy |
| Measure Participants | 4 | 6 | 5 |
| Capecitabine, Day 1, n= 2, 4, 3 |
1440
(750)
|
3080
(1340)
|
1890
(1420)
|
| Capecitabine, Day 14, n=2,2,2 |
2100
(1770)
|
5440
(3270)
|
3710
(156)
|
| 5'-DFCR, Day 1, n=2,4,3 |
2050
(813)
|
2190
(626)
|
2180
(1690)
|
| 5'-DFCR, Day 14, n=2,2,2 |
2980
(2020)
|
3500
(1470)
|
3200
(233)
|
| 5'-DFUR, Day 1, n=2,4,3 |
1910
(834)
|
2640
(1700)
|
3770
(3300)
|
| 5'-DFUR, Day 14, n=2,2,2 |
3300
(2800)
|
3120
(445)
|
5020
(1220)
|
| FBAL, Day 1, n=2,4,3 |
1350
(134)
|
1740
(365)
|
2050
(1640)
|
| FBAL, Day 14, n=2,2,2 |
1770
(410)
|
2430
(84.9)
|
2140
(304)
|
| Title | Time to Maximum Plasma Concentration (Tmax) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) |
|---|---|
| Description | Tmax is the corresponding time at which Cmax occurs of capecitabine and its metabolites.Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline [pre-dose], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline [pre-dose], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing). |
| Time Frame | Day 1 and Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population consisted of all eligible patients who received at least one dose of capecitabine. Participants available at a particular time point were included in analysis. |
| Arm/Group Title | Capecitabine 500 mg/m^2 | Capecitabine 650 mg/m^2 | Capecitabine 850 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Capecitabine 500 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 650 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 850 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy |
| Measure Participants | 4 | 6 | 5 |
| Capecitabine, Day 1, n= 2, 4, 3 |
0.58
|
0.63
|
0.85
|
| Capecitabine, Day 14, n=2,2,2 |
1.33
|
0.82
|
0.61
|
| 5'-DFCR, Day 1, n=2,4,3 |
1.0
|
0.75
|
1.55
|
| 5'-DFCR, Day 14, n=2,2,2 |
1.49
|
1.18
|
0.61
|
| 5'-DFUR, Day 1, n=2,4,3 |
1
|
0.9
|
1.5
|
| 5'-DFUR, Day 14, n=2,2,2 |
1.5
|
0.82
|
0.61
|
| 5-FU, Day 1, n=2,4,3 |
1
|
0.75
|
1.5
|
| 5-FU, Day 14, n=2,2,2 |
1.5
|
0.83
|
1
|
| FBAL, Day 1, n=2,4,3 |
2.53
|
1.5
|
1.55
|
| FBAL, Day 14, n=2,2,2 |
1.74
|
2.2
|
2.03
|
| Title | The Area Under the Plasma Concentration-time Curve From Time of Dosing to the Last Measurable Concentration (AUClast) of Capecitabine and Its Metabolites (5'-DFCR, 5'-DFUR, 5-FU and FBAL) |
|---|---|
| Description | AUC last concentration of capecitabine and its metabolites. Participants who consented to participating in the PK studies were randomized to either sampling series A or Series B. The collection time points included 2 different series, Series A (Baseline [pre-dose], 10 mins, 30 mins, 1, 2.5, 6, 8 and 10 hours after dosing) and Series B (Baseline [pre-dose], 15 minutes, 45 minutes, 1.5, 4, 8 and 10 hours after dosing). |
| Time Frame | Day 1 and Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population consisted of all eligible patients who received at least one dose of capecitabine. Participants available at a particular time point were included in analysis. |
| Arm/Group Title | Capecitabine 500 mg/m^2 | Capecitabine 650 mg/m^2 | Capecitabine 850 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Capecitabine 500 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 650 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 850 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy |
| Measure Participants | 4 | 6 | 5 |
| Capecitabine, Day 1, n= 2, 4, 3 |
3370
(607)
|
5160
(3700)
|
3470
(1170)
|
| Capecitabine, Day 14, n=2,2,2 |
2890
(655)
|
9660
(3340)
|
5670
(971)
|
| 5'-DFCR, Day 1, n=2,4,3 |
5250
(755)
|
5140
(3440)
|
4180
(2380)
|
| 5'-DFCR, Day 14, n=2,2,2 |
4300
(27.2)
|
9250
(1400)
|
6520
(452)
|
| 5'-DFUR, Day 1, n=2,4,3 |
4790
(784)
|
4300
(1600)
|
6650
(3740)
|
| 5'-DFUR, Day 14, n=2,2,2 |
4240
(929)
|
8010
(1890)
|
10500
(445)
|
| 5-FU Day 1, n=2,4,3 |
81.6
(29.7)
|
114
(40.9)
|
271
(205)
|
| 5-FU Day 14, n=2,2,2 |
181
(84.7)
|
253
(16.3)
|
499
(78.8)
|
| FBAL, Day 1, n=2,4,3 |
5990
(951)
|
8110
(1640)
|
7010
(4490)
|
| FBAL, Day 14, n=2,2,2 |
5720
(690)
|
10700
(574)
|
10400
(1760)
|
| Title | Anti Tumor Activity |
|---|---|
| Description | Tumor response refers to the best response prior to failure (disease progression, death or second malignancy). |
| Time Frame | Up to 6 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy data of the present study (NO18517 - NCT00532948) were pre-specified to be combined with efficacy data of the Phase 2 portion of this Study, NO21125 (NCT01118377) for analysis. Results are currently posted in the record of Study NO21125. |
| Arm/Group Title | Capecitabine 500 mg/m^2 | Capecitabine 650 mg/m^2 | Capecitabine 850 mg/m^2 |
|---|---|---|---|
| Arm/Group Description | Capecitabine 500 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 650 mg/m^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 850 mg/m^2 was administered twice daily (ideally administered daily in two divided doses approximately 12 hours apart beginning within 24 hours of the start of radiation therapy) for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy |
| Measure Participants | 0 | 0 | 0 |
Adverse Events
| Time Frame | Up to 6 years | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Capecitabine 500 mg/m^2 | Capecitabine 650 mg/m^2 | Capecitabine 850 mg/m^2 | |||
| Arm/Group Description | Capecitabine 500 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 650 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | Capecitabine 850 mg/m^2 was administered twice daily for 14 days, followed by 7 day rest. Treatment was administered for three cycles with radiation therapy period and 3 cycles without radiation therapy | |||
All Cause Mortality |
||||||
| Capecitabine 500 mg/m^2 | Capecitabine 650 mg/m^2 | Capecitabine 850 mg/m^2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Capecitabine 500 mg/m^2 | Capecitabine 650 mg/m^2 | Capecitabine 850 mg/m^2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/4 (50%) | 1/12 (8.3%) | 3/6 (50%) | |||
| Blood and lymphatic system disorders | ||||||
| Leukopenia | 1/4 (25%) | 0/12 (0%) | 0/6 (0%) | |||
| General disorders | ||||||
| Pain | 0/4 (0%) | 1/12 (8.3%) | 0/6 (0%) | |||
| Infections and infestations | ||||||
| Abdominal Infection | 0/4 (0%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Investigations | ||||||
| Blood Creatinine Increased | 0/4 (0%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Metabolism and nutrition disorders | ||||||
| Hyperglycaemia | 0/4 (0%) | 1/12 (8.3%) | 0/6 (0%) | |||
| Nervous system disorders | ||||||
| Convulsion | 0/4 (0%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Hydrocephalus | 1/4 (25%) | 0/12 (0%) | 0/6 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis Exfoliative | 0/4 (0%) | 1/12 (8.3%) | 0/6 (0%) | |||
| Skin Exfoliation | 0/4 (0%) | 0/12 (0%) | 1/6 (16.7%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Capecitabine 500 mg/m^2 | Capecitabine 650 mg/m^2 | Capecitabine 850 mg/m^2 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/4 (75%) | 12/12 (100%) | 6/6 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Lymphopenia | 3/4 (75%) | 10/12 (83.3%) | 3/6 (50%) | |||
| Leukopenia | 3/4 (75%) | 10/12 (83.3%) | 2/6 (33.3%) | |||
| Cardiac disorders | ||||||
| Hypertension | 1/4 (25%) | 2/12 (16.7%) | 0/6 (0%) | |||
| Endocrine disorders | ||||||
| Cushingoid | 0/4 (0%) | 2/12 (16.7%) | 1/6 (16.7%) | |||
| Eye disorders | ||||||
| Diplopia | 2/4 (50%) | 0/12 (0%) | 0/6 (0%) | |||
| Extraocular muscle disorder | 1/4 (25%) | 0/12 (0%) | 0/6 (0%) | |||
| Vision blurred | 1/4 (25%) | 0/12 (0%) | 0/6 (0%) | |||
| Gastrointestinal disorders | ||||||
| Vomiting | 2/4 (50%) | 9/12 (75%) | 2/6 (33.3%) | |||
| Abdominal pain | 0/4 (0%) | 4/12 (33.3%) | 4/6 (66.7%) | |||
| Nausea | 1/4 (25%) | 2/12 (16.7%) | 4/6 (66.7%) | |||
| Constipation | 1/4 (25%) | 3/12 (25%) | 2/6 (33.3%) | |||
| Diarrhoea | 2/4 (50%) | 3/12 (25%) | 1/6 (16.7%) | |||
| Abdominal discomfort | 0/4 (0%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Infections and infestations | ||||||
| Gingival infection | 0/4 (0%) | 0/12 (0%) | 2/6 (33.3%) | |||
| Nasopharyngitis | 1/4 (25%) | 1/12 (8.3%) | 0/6 (0%) | |||
| Otitis media | 1/4 (25%) | 1/12 (8.3%) | 0/6 (0%) | |||
| Respiratory tract infection | 1/4 (25%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Injury, poisoning and procedural complications | ||||||
| Radiation mucositis | 1/4 (25%) | 1/12 (8.3%) | 1/6 (16.7%) | |||
| Thermal burn | 1/4 (25%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Investigations | ||||||
| Alanine aminotransferase increased | 1/4 (25%) | 9/12 (75%) | 3/6 (50%) | |||
| Haemoglobin | 1/4 (25%) | 4/12 (33.3%) | 2/6 (33.3%) | |||
| Neutrophil count | 2/4 (50%) | 4/12 (33.3%) | 1/6 (16.7%) | |||
| Platelet count decreased | 2/4 (50%) | 5/12 (41.7%) | 0/6 (0%) | |||
| Weight increased | 1/4 (25%) | 3/12 (25%) | 2/6 (33.3%) | |||
| Aspartate aminotransferase increased | 0/4 (0%) | 2/12 (16.7%) | 1/6 (16.7%) | |||
| Blood bicarbonate decreased | 1/4 (25%) | 1/12 (8.3%) | 1/6 (16.7%) | |||
| Blood alkaline phosphatase increased | 0/4 (0%) | 1/12 (8.3%) | 1/6 (16.7%) | |||
| Gamma-glutamyltransferase increased | 0/4 (0%) | 1/12 (8.3%) | 1/6 (16.7%) | |||
| Blood creatinine increased | 0/4 (0%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Weight Decreased | 0/4 (0%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypokalaemia | 2/4 (50%) | 3/12 (25%) | 2/6 (33.3%) | |||
| Hyperglycaemia | 1/4 (25%) | 3/12 (25%) | 2/6 (33.3%) | |||
| Hypoalbuminaemia | 2/4 (50%) | 3/12 (25%) | 1/6 (16.7%) | |||
| Hypocalcaemia | 1/4 (25%) | 4/12 (33.3%) | 1/6 (16.7%) | |||
| Decreased appetite | 2/4 (50%) | 2/12 (16.7%) | 1/6 (16.7%) | |||
| Hypercalcaemia | 1/4 (25%) | 3/12 (25%) | 1/6 (16.7%) | |||
| Hypermagnesaemia | 1/4 (25%) | 4/12 (33.3%) | 0/6 (0%) | |||
| Hyponatraemia | 0/4 (0%) | 4/12 (33.3%) | 1/6 (16.7%) | |||
| Hypophosphataemia | 2/4 (50%) | 2/12 (16.7%) | 1/6 (16.7%) | |||
| Hypernatraemia | 1/4 (25%) | 1/12 (8.3%) | 0/6 (0%) | |||
| Dehydration | 1/4 (25%) | 0/12 (0%) | 0/6 (0%) | |||
| Hypoglycaemia | 1/4 (25%) | 0/12 (0%) | 0/6 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 1/4 (25%) | 2/12 (16.7%) | 0/6 (0%) | |||
| Muscular weakness | 0/4 (0%) | 3/12 (25%) | 0/6 (0%) | |||
| Neck pain | 1/4 (25%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Nervous system disorders | ||||||
| Headache | 2/4 (50%) | 4/12 (33.3%) | 2/6 (33.3%) | |||
| Convulsion | 1/4 (25%) | 1/12 (8.3%) | 1/6 (16.7%) | |||
| Dizziness | 1/4 (25%) | 2/12 (16.7%) | 0/6 (0%) | |||
| Facial nerve disorder | 1/4 (25%) | 2/12 (16.7%) | 0/6 (0%) | |||
| VIth nerve disorder | 1/4 (25%) | 2/12 (16.7%) | 0/6 (0%) | |||
| Ataxia | 1/4 (25%) | 1/12 (8.3%) | 0/6 (0%) | |||
| Glossopharyngeal nerve disorder | 1/4 (25%) | 0/12 (0%) | 0/6 (0%) | |||
| Nystagmus | 1/4 (25%) | 0/12 (0%) | 0/6 (0%) | |||
| Peripheral motor neuropathy | 1/4 (25%) | 0/12 (0%) | 0/6 (0%) | |||
| Tremor | 1/4 (25%) | 0/12 (0%) | 0/6 (0%) | |||
| Psychiatric disorders | ||||||
| Confusional state | 0/4 (0%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Euphoric mood | 0/4 (0%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Psychotic Disorder | 0/4 (0%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Epistaxis | 1/4 (25%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Cough | 1/4 (25%) | 0/12 (0%) | 0/6 (0%) | |||
| Rhinitis allergic | 0/4 (0%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Skin exfoliation | 1/4 (25%) | 8/12 (66.7%) | 4/6 (66.7%) | |||
| Alopecia | 1/4 (25%) | 4/12 (33.3%) | 1/6 (16.7%) | |||
| Skin hyperpigmentation | 1/4 (25%) | 2/12 (16.7%) | 3/6 (50%) | |||
| Dermatitis exfoliative | 0/4 (0%) | 4/12 (33.3%) | 1/6 (16.7%) | |||
| Dry skin | 0/4 (0%) | 3/12 (25%) | 0/6 (0%) | |||
| Pruritus | 0/4 (0%) | 2/12 (16.7%) | 1/6 (16.7%) | |||
| Hyperhidrosis | 1/4 (25%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Acne | 0/4 (0%) | 0/12 (0%) | 1/6 (16.7%) | |||
| Surgical and medical procedures | ||||||
| Oculomotor nerve operation | 1/4 (25%) | 0/12 (0%) | 0/6 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Roche Trial Information Hotline |
|---|---|
| Organization | Hoffmann-La Roche AG |
| Phone | +41 61 6878333 |
| global.trial_information@roche.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00532948
Other Study ID Numbers:
- NO18517
First Posted:
Sep 21, 2007
Last Update Posted:
Dec 7, 2016
Last Verified:
Oct 1, 2016