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Clinical Trial Results:
A Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Palifermin (Recombinant Human Keratinocyte Growth Factor) for Reduction of Oral Mucositis in Subjects With Stage 2B or 3 Locally Advanced, Colon Cancer Receiving 5-FU and Leucovorin as Adjuvant Therapy
| Summary | |
EudraCT number | 2004-005007-14 |
Trial protocol | HU CZ BE |
Global end of trial date | 31 Mar 2014 |
| Results information | |
Results version number | v1(current) |
This version publication date | 04 May 2017 |
First version publication date | 04 May 2017 |
Other versions | |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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| Trial identification | |||
Sponsor protocol code | 20040122 | ||
| Additional study identifiers | |||
ISRCTN number | - | ||
US NCT number | NCT00393822 | ||
WHO universal trial number (UTN) | - | ||
| Sponsors | |||
Sponsor organisation name | Amgen, Inc. | ||
Sponsor organisation address | One Amgen Center Drive, Thousand Oaks, CA, United States, 91320 | ||
Public contact | IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com | ||
Scientific contact | IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com | ||
| Paediatric regulatory details | |||
Is trial part of an agreed paediatric investigation plan (PIP) | No | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? | No | ||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? | No | ||
| Results analysis stage | |||
Analysis stage | Final | ||
Date of interim/final analysis | 31 Mar 2014 | ||
Is this the analysis of the primary completion data? | No | ||
Global end of trial reached? | Yes | ||
Global end of trial date | 31 Mar 2014 | ||
Was the trial ended prematurely? | No | ||
| General information about the trial | |||
Main objective of the trial | The primary objective was to evaluate the efficacy of palifermin in reducing the incidence of grade ≥ 2 oral mucositis (OM) in subjects with stage 2B or stage 3 locally advanced colon cancer undergoing adjuvant chemotherapy with 5-fluorouracil (5-FU) and leucovorin (LV). | ||
Protection of trial subjects | This study was conducted in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines. All subjects provided written informed consent before undergoing any study-related procedures, including screening procedures. The study protocol, amendments, and the informed consent form (ICF) were reviewed by the Institutional Review Boards (IRBs) and Independent Ethics Committees (IECs). No subjects were recruited into the study and no investigational product (IP) was shipped until the IRB/IEC gave written approval of the protocol and ICF and Amgen received copies of these approvals. | ||
Background therapy | - | ||
Evidence for comparator | - | ||
Actual start date of recruitment | 11 Aug 2005 | ||
Long term follow-up planned | Yes | ||
Long term follow-up rationale | Efficacy | ||
Long term follow-up duration | 5 Years | ||
Independent data monitoring committee (IDMC) involvement? | Yes | ||
| Population of trial subjects | |||
Number of subjects enrolled per country | |||
Country: Number of subjects enrolled | Poland: 40 | ||
Country: Number of subjects enrolled | Hungary: 38 | ||
Country: Number of subjects enrolled | Belgium: 18 | ||
Country: Number of subjects enrolled | Czech Republic: 4 | ||
Worldwide total number of subjects | 100 | ||
EEA total number of subjects | 100 | ||
Number of subjects enrolled per age group | |||
In utero | 0 | ||
Preterm newborn - gestational age | 0 | ||
Newborns (0-27 days) | 0 | ||
Infants and toddlers (28 days-23 months) | 0 | ||
Children (2-11 years) | 0 | ||
Adolescents (12-17 years) | 0 | ||
Adults (18-64 years) | 51 | ||
From 65 to 84 years | 49 | ||
85 years and over | 0 | ||
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| Recruitment | |||||||||||||||||||||||||||||||
Recruitment details | This study was conducted at 23 sites in 4 European Union (EU) countries, of which 14 sites randomized subjects. | ||||||||||||||||||||||||||||||
| Pre-assignment | |||||||||||||||||||||||||||||||
Screening details | Eligible subjects were randomized at a 1:1 ratio to receive palifermin or placebo through an Interactive Voice Response System (IVRS). The randomization was stratified by the following 4 disease stage/grade strata: • 2B Low Grade, 3A Low Grade • 2B High Grade, 3A High Grade • Stage 3B – all grades • Stage 3C – all grades | ||||||||||||||||||||||||||||||
| Period 1 | |||||||||||||||||||||||||||||||
Period 1 title | Overall Study (overall period) | ||||||||||||||||||||||||||||||
Is this the baseline period? | Yes | ||||||||||||||||||||||||||||||
Allocation method | Randomised - controlled | ||||||||||||||||||||||||||||||
Blinding used | Double blind | ||||||||||||||||||||||||||||||
Roles blinded | Subject, Investigator | ||||||||||||||||||||||||||||||
| Arms | |||||||||||||||||||||||||||||||
Are arms mutually exclusive | Yes | ||||||||||||||||||||||||||||||
| Arm title | Placebo | ||||||||||||||||||||||||||||||
Arm description | Participants received adjuvant chemotherapy with 20 mg/m² leucovorin administered by intravenous (IV) injection followed by an IV bolus infusion of 425 mg/m² 5-fluorouracil (5-FU) daily for 5 consecutive days beginning on day 1 of each 28-day treatment cycle, for a total of up to 6 cycles. A single dose of placebo to palifermin administered as a bolus IV injection was given three days prior to each cycle of chemotherapy for up to 6 doses. Starting in cycle 2, the 5-FU dose could have been decreased by 20% for toxicity. | ||||||||||||||||||||||||||||||
Arm type | Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product name | Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product code | |||||||||||||||||||||||||||||||
Other name | |||||||||||||||||||||||||||||||
Pharmaceutical forms | Powder for solution for injection | ||||||||||||||||||||||||||||||
Routes of administration | Intravenous bolus use | ||||||||||||||||||||||||||||||
Dosage and administration details | Administered as a bolus intravenous (IV) injection over 15-20 seconds. | ||||||||||||||||||||||||||||||
| Arm title | Palifermin | ||||||||||||||||||||||||||||||
Arm description | Participants received adjuvant chemotherapy with 20 mg/m² leucovorin administered by intravenous (IV) injection followed by an IV bolus infusion of 425 mg/m² 5-fluorouracil (5-FU) daily for 5 consecutive days beginning on day 1 of each 28-day treatment cycle, for a total of up to 6 cycles. A single dose of 120 µg/kg palifermin administered as a bolus IV injection was given three days prior to each cycle of chemotherapy for up to 6 doses. Starting in cycle 2, the 5-FU dose could have been decreased by 20% for toxicity. | ||||||||||||||||||||||||||||||
Arm type | Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name | Palifermin | ||||||||||||||||||||||||||||||
Investigational medicinal product code | |||||||||||||||||||||||||||||||
Other name | Kepivance | ||||||||||||||||||||||||||||||
Pharmaceutical forms | Powder for solution for injection | ||||||||||||||||||||||||||||||
Routes of administration | Intravenous bolus use | ||||||||||||||||||||||||||||||
Dosage and administration details | Palifermin 120 μg/kg administered as a bolus intravenous (IV) injection over 15-20 seconds. | ||||||||||||||||||||||||||||||
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| Baseline characteristics reporting groups | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title | Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description | Participants received adjuvant chemotherapy with 20 mg/m² leucovorin administered by intravenous (IV) injection followed by an IV bolus infusion of 425 mg/m² 5-fluorouracil (5-FU) daily for 5 consecutive days beginning on day 1 of each 28-day treatment cycle, for a total of up to 6 cycles. A single dose of placebo to palifermin administered as a bolus IV injection was given three days prior to each cycle of chemotherapy for up to 6 doses. Starting in cycle 2, the 5-FU dose could have been decreased by 20% for toxicity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title | Palifermin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description | Participants received adjuvant chemotherapy with 20 mg/m² leucovorin administered by intravenous (IV) injection followed by an IV bolus infusion of 425 mg/m² 5-fluorouracil (5-FU) daily for 5 consecutive days beginning on day 1 of each 28-day treatment cycle, for a total of up to 6 cycles. A single dose of 120 µg/kg palifermin administered as a bolus IV injection was given three days prior to each cycle of chemotherapy for up to 6 doses. Starting in cycle 2, the 5-FU dose could have been decreased by 20% for toxicity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| End points reporting groups | |||
Reporting group title | Placebo | ||
Reporting group description | Participants received adjuvant chemotherapy with 20 mg/m² leucovorin administered by intravenous (IV) injection followed by an IV bolus infusion of 425 mg/m² 5-fluorouracil (5-FU) daily for 5 consecutive days beginning on day 1 of each 28-day treatment cycle, for a total of up to 6 cycles. A single dose of placebo to palifermin administered as a bolus IV injection was given three days prior to each cycle of chemotherapy for up to 6 doses. Starting in cycle 2, the 5-FU dose could have been decreased by 20% for toxicity. | ||
Reporting group title | Palifermin | ||
Reporting group description | Participants received adjuvant chemotherapy with 20 mg/m² leucovorin administered by intravenous (IV) injection followed by an IV bolus infusion of 425 mg/m² 5-fluorouracil (5-FU) daily for 5 consecutive days beginning on day 1 of each 28-day treatment cycle, for a total of up to 6 cycles. A single dose of 120 µg/kg palifermin administered as a bolus IV injection was given three days prior to each cycle of chemotherapy for up to 6 doses. Starting in cycle 2, the 5-FU dose could have been decreased by 20% for toxicity. | ||
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End point title | Number of Participants with Grade ≥ 2 Oral Mucositis in Cycle 1 | |||||||||
End point description | Oral mucositis (OM) assessments were performed by a trained evaluator according to the world health organization (WHO) Toxicity Criteria for grading oral mucositis: - Grade 0: None; - Grade 1: Soreness, erythema; - Grade 2: Erythema, ulcers, ability to eat solids; - Grade 3: Ulcers, requires liquid diet; - Grade 4: Alimentation not possible. This analysis was performed n the full analysis set which includes all randomized participants. | |||||||||
End point type | Primary | |||||||||
End point timeframe | Cycle 1, 28 days | |||||||||
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Statistical analysis title | Primary Analysis | |||||||||
Statistical analysis description | The null hypothesis for this study was that the incidence of grade ≥ 2 OM (WHO scale) would be the same between the placebo group and the palifermin group. The alternative hypothesis was that the incidence of grade ≥ 2 OM (WHO scale) between palifermin and placebo group would be different. | |||||||||
Comparison groups | Placebo v Palifermin | |||||||||
Number of subjects included in analysis | 100 | |||||||||
Analysis specification | Pre-specified | |||||||||
Analysis type | superiority | |||||||||
P-value | = 0.9149 [1] | |||||||||
Method | Cochran-Mantel-Haenszel | |||||||||
Parameter type | Difference in proportions | |||||||||
Point estimate | -0.01 | |||||||||
Confidence interval | ||||||||||
level | 95% | |||||||||
sides | 2-sided | |||||||||
lower limit | -0.16 | |||||||||
upper limit | 0.14 | |||||||||
| Notes [1] - Generalized Cochran-Mantel-Haenszel test for general association with randomization strata as analysis stratification factor. | ||||||||||
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End point title | Number of Participants with Grade ≥ 2 Oral Mucositis in Cycle 2 | |||||||||
End point description | Oral mucositis assessments were performed by a trained evaluator according to the world health organization (WHO) Toxicity Criteria for grading oral mucositis: Grade 0: None; Grade 1: Soreness, erythema; Grade 2: Erythema, ulcers, ability to eat solids; Grade 3: Ulcers, requires liquid diet; Grade 4: Alimentation not possible. This analysis was performed in the Efficacy Evaluable Subset for Cycle 2 which includes all subjects who were randomized and received investigational product on day –3 and at least one dose of 5-FU in cycle 2. | |||||||||
End point type | Secondary | |||||||||
End point timeframe | Cycle 2 (28 days) | |||||||||
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Statistical analysis title | Statistical Analysis | |||||||||
Comparison groups | Placebo v Palifermin | |||||||||
Number of subjects included in analysis | 92 | |||||||||
Analysis specification | Pre-specified | |||||||||
Analysis type | superiority | |||||||||
P-value | = 0.7189 [2] | |||||||||
Method | Cochran-Mantel-Haenszel | |||||||||
Parameter type | Difference in proportions | |||||||||
Point estimate | 0.02 | |||||||||
Confidence interval | ||||||||||
level | 95% | |||||||||
sides | 2-sided | |||||||||
lower limit | -0.1 | |||||||||
upper limit | 0.14 | |||||||||
| Notes [2] - Generalized Cochran-Mantel-Haenszel test for general association with randomization strata as analysis stratification factor. | ||||||||||
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End point title | Average Mouth and Throat Soreness (MTS) Score in Cycle 1 | ||||||||||||
End point description | Mouth and throat soreness was assessed by Question 2 of the Oral Mucositis Daily Questionnaire (OMDQ): "During the past 24 hours, how much mouth and throat soreness did you have?" The question was answered using a verbal descriptive scale with 5 response categories from 0 (no soreness) to 4 (extreme soreness). This endpoint was analyzed in the PRO Evaluable Subset for Cycle 1 which included all randomized subjects that had a valid baseline assessment for MTS (question 2 of the OMDQ) and either at least 2 assessments each week for MTS in cycles 1 and/or 2, or 70% or greater overall compliance for MTS in cycles 1 and/or 2. | ||||||||||||
End point type | Secondary | ||||||||||||
End point timeframe | Cycle 1 (28 days) | ||||||||||||
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Statistical analysis title | Statistical Anlaysis | ||||||||||||
Comparison groups | Placebo v Palifermin | ||||||||||||
Number of subjects included in analysis | 92 | ||||||||||||
Analysis specification | Pre-specified | ||||||||||||
Analysis type | superiority | ||||||||||||
P-value | = 0.9397 [3] | ||||||||||||
Method | Cochran-Mantel-Haenszel | ||||||||||||
Parameter type | Difference in MTS Score | ||||||||||||
Point estimate | -0.06 | ||||||||||||
Confidence interval | |||||||||||||
level | 95% | ||||||||||||
sides | 2-sided | ||||||||||||
lower limit | -0.26 | ||||||||||||
upper limit | 0.13 | ||||||||||||
| Notes [3] - Generalized Cochran-Mantel-Haenszel test for mean score difference using modified ridit score with randomization strata as analysis stratification factor. | |||||||||||||
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End point title | Average Mouth and Throat Soreness (MTS) Score in Cycle 2 | ||||||||||||
End point description | Mouth and throat soreness was assessed by Question 2 of the Oral Mucositis Daily Questionnaire (OMDQ): "During the past 24 hours, how much mouth and throat soreness did you have?" The question was answered using a verbal descriptive scale with 5 response categories from 0 (no soreness) to 4 (extreme soreness). This endpoint was analyzed in the PRO Evaluable Subset for Cycle 2 which included all randomized subjects who received investigational product on Day –3 and at least one dose of 5-FU in that cycle 2 that had a valid baseline assessment for MTS (question 2 of the OMDQ) and either at least 2 assessments each week for MTS in cycles 1 and/or 2, or 70% or greater overall compliance for MTS in cycles 1 and/or 2. | ||||||||||||
End point type | Secondary | ||||||||||||
End point timeframe | Cycle 2 (28 days) | ||||||||||||
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Statistical analysis title | Statistical Analysis | ||||||||||||
Comparison groups | Placebo v Palifermin | ||||||||||||
Number of subjects included in analysis | 87 | ||||||||||||
Analysis specification | Pre-specified | ||||||||||||
Analysis type | superiority | ||||||||||||
P-value | = 0.4569 [4] | ||||||||||||
Method | Cochran-Mantel-Haenszel | ||||||||||||
Parameter type | Difference in MTS Score | ||||||||||||
Point estimate | 0.02 | ||||||||||||
Confidence interval | |||||||||||||
level | 95% | ||||||||||||
sides | 2-sided | ||||||||||||
lower limit | -0.16 | ||||||||||||
upper limit | 0.21 | ||||||||||||
| Notes [4] - Generalized Cochran-Mantel-Haenszel test for mean score difference using modified ridit score with randomization strata as analysis stratification factor. | |||||||||||||
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End point title | Number of Participants with 5-FU Dose Changes, Dose Delays, or Not Receiving a Dose in Cycle 2 | |||||||||
End point description | ||||||||||
End point type | Secondary | |||||||||
End point timeframe | Cycle 2 (28 days) | |||||||||
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Statistical analysis title | Statistical Analysis | |||||||||
Comparison groups | Placebo v Palifermin | |||||||||
Number of subjects included in analysis | 100 | |||||||||
Analysis specification | Pre-specified | |||||||||
Analysis type | superiority | |||||||||
P-value | = 0.8461 [5] | |||||||||
Method | Cochran-Mantel-Haenszel | |||||||||
Parameter type | Difference in proportions | |||||||||
Point estimate | 0.02 | |||||||||
Confidence interval | ||||||||||
level | 95% | |||||||||
sides | 2-sided | |||||||||
lower limit | -0.17 | |||||||||
upper limit | 0.21 | |||||||||
| Notes [5] - Generalized Cochran-Mantel-Haenszel test for general association with randomization strata as analysis stratification factor. | ||||||||||
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End point title | Duration of Grade ≥ 2 Oral Mucositis in Cycle 1 | ||||||||||||
End point description | Duration of grade ≥ 2 oral mucositis was calculated from the onset of grade ≥ 2 OM (first time WHO grade 2, 3 or 4 was observed) to the resolution of this event (first time WHO grade 0 or 1 was observed after last WHO grade 2, 3 or 4). This endpoint was analyzed in participants who experienced a grade 2, 3 or 4 oral mucositis event in cycle 1. | ||||||||||||
End point type | Secondary | ||||||||||||
End point timeframe | Cycle 1 (28 days) | ||||||||||||
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| No statistical analyses for this end point | |||||||||||||
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End point title | Duration of Grade ≥ 2 Oral Mucositis in Cycle 2 | ||||||||||||
End point description | Duration of grade ≥ 2 oral mucositis was calculated from the onset of grade ≥ 2 OM (first time WHO grade 2, 3 or 4 was observed) to the resolution of this event (first time WHO grade 0 or 1 was observed after last WHO grade 2, 3 or 4). This endpoint was analyzed in participants who experienced a grade 2, 3 or 4 oral mucositis event in cycle 2. | ||||||||||||
End point type | Secondary | ||||||||||||
End point timeframe | Cycle 2 (28 days) | ||||||||||||
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| No statistical analyses for this end point | |||||||||||||
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End point title | Number of Participants with Adverse Events During the Treatment Period | |||||||||||||||||||||||||||||||||||||||
End point description | The severity of adverse events (AEs) was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3. The relationship of adverse events to the investigational product was assessed by the investigator. A protocol-specific limiting toxicity (PSLT) was defined as any non-hematologic grade ≥ 3 (CTCAE v3.0) adverse event considered related to investigational product (IP) that prompts discontinuation of investigational product with the exception of non-symptomatic elevated amylase and/or lipase serum levels. | |||||||||||||||||||||||||||||||||||||||
End point type | Secondary | |||||||||||||||||||||||||||||||||||||||
End point timeframe | From the first dose of investigational drug (placebo or palifermin) until 30 days after last dose (approximately 7 months) | |||||||||||||||||||||||||||||||||||||||
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||
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End point title | Number of Participants with Anti-Palifermin Antibody Formation | ||||||||||||||||||
End point description | This endpoint was analyzed in participants who received investigational product and who had measurements at each time point. | ||||||||||||||||||
End point type | Secondary | ||||||||||||||||||
End point timeframe | Samples for antibody analysis were collected on cycle 1 day -3, cycle 3, day -3 and at the end of treatment visit | ||||||||||||||||||
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title | Number of Participants with Progression-free Survival at the End of Treatment | |||||||||
End point description | Disease progression was assessed by computed tomography (CT) scans of the chest abdomen and pelvis. The number of participants with progression-free survival is the number of subjects alive and progression free at the end of treatment visit. | |||||||||
End point type | Secondary | |||||||||
End point timeframe | 6 months | |||||||||
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| No statistical analyses for this end point | ||||||||||
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End point title | Number of Participants with Second Primary Tumors at the End of Long-term Follow-up | |||||||||
End point description | ||||||||||
End point type | Secondary | |||||||||
End point timeframe | From first dose of investigational product until the end of the long-term follow-up period; the median (minimum, maximum) follow-up duration was 313 (47, 436) weeks for the placebo group and 321 (8, 430) weeks for the palifermin group. | |||||||||
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| No statistical analyses for this end point | ||||||||||
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End point title | Number of Participants with Other Malignancies at the End of Long-term Follow-up | |||||||||
End point description | ||||||||||
End point type | Secondary | |||||||||
End point timeframe | From first dose of investigational product until the end of the long-term follow-up period; the median (minimum, maximum) follow-up duration was 313 (47, 436) weeks for the placebo group and 321 (8, 430) weeks for the palifermin group. | |||||||||
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| No statistical analyses for this end point | ||||||||||
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End point title | Number of Participants with Tumor Progression or Recurrence of Primary Disease at the End of Long-term Follow-up | |||||||||
End point description | ||||||||||
End point type | Secondary | |||||||||
End point timeframe | From first dose of investigational product until the end of the long-term follow-up period; the median (minimum, maximum) follow-up duration was 313 (47, 436) weeks for the placebo group and 321 (8, 430) weeks for the palifermin group. | |||||||||
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| No statistical analyses for this end point | ||||||||||
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End point title | Number of Deaths at the End of Long-term Follow-up | |||||||||
End point description | ||||||||||
End point type | Secondary | |||||||||
End point timeframe | From first dose of investigational product until the end of the long-term follow-up period; The median (minimum, maximum) follow-up duration was 313 (47, 436) weeks for the placebo group and 321 (8, 430) weeks for the palifermin group. | |||||||||
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| No statistical analyses for this end point | ||||||||||
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| Adverse events information | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events | From the first dose of investigational drug (placebo or palifermin) until 30 days after last dose (approximately 7 months) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type | Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dictionary used for adverse event reporting | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name | MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version | 11.0 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Reporting groups | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title | Placebo | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description | Participants received adjuvant chemotherapy with 20 mg/m² leucovorin administered by intravenous (IV) injection followed by an IV bolus infusion of 425 mg/m² 5-fluorouracil (5-FU) daily for 5 consecutive days beginning on day 1 of each 28-day treatment cycle, for a total of up to 6 cycles. A single dose of placebo to palifermin administered as a bolus IV injection was given three days prior to each cycle of chemotherapy for up to 6 doses. Starting in cycle 2, the 5-FU dose could have been decreased by 20% for toxicity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title | Palifermin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description | Participants received adjuvant chemotherapy with 20 mg/m² leucovorin administered by intravenous (IV) injection followed by an IV bolus infusion of 425 mg/m² 5-fluorouracil (5-FU) daily for 5 consecutive days beginning on day 1 of each 28-day treatment cycle, for a total of up to 6 cycles. A single dose of 120 µg/kg palifermin administered as a bolus IV injection was given three days prior to each cycle of chemotherapy for up to 6 doses. Starting in cycle 2, the 5-FU dose could have been decreased by 20% for toxicity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) | |||
| Were there any global substantial amendments to the protocol? Yes | |||
Date | Amendment | ||
24 May 2005 | Amendment 1 instituted the following changes: • Following a data monitoring committee (DMC) review of available safety data from subjects who received the 180 μg/kg dose in the setting of radiation therapy with concomitant chemotherapy, the dose was reduced to 120 μg/kg in patients with advanced head and neck cancer post-surgery as recommended by the DMC. This recommendation was made based on the review of safety data after application of palifermin at a weekly dose of 180 μg/kg, which has been associated with limited local swelling in areas of previous surgery or epithelial injury (eg, tracheotomy or tumor surgery). A previous pharmacokinetic-pharmacodynamics study in young, male adults receiving single palifermin doses of 60 to 250 μg/kg (study 20010192) showed a dose-response in palifermin biological activity (as measured by buccal mucosal epithelial cell proliferation) with a plateau between the doses of 160 μg/kg and 210 μg/kg. Based on our commitment first and foremost to patient safety, Amgen followed the DMC recommendation and also made the decision to implement the same dose reduction in this study in colon cancer post-surgery. All 100 subjects enrolled into this study (20040122) received the 120 μg/kg dose. • The safety section of the Subject Informed Consent Template was updated with additional information. • The patient reported outcomes (PRO) sections were clarified to ensure consistency across the palifermin program. • Additional laboratory parameters (hematocrit and blood urea nitrogen or urea) were added. • At the time when all subjects completed the first 2 cycles of chemotherapy (ie, completed all efficacy assessments), the data were unblinded and the final analysis of all efficacy endpoints was performed. | ||
30 Jan 2008 | Amendment 2 was written to clarify and reduce the study objectives and the corresponding analyses as follows: • The primary objective wording was changed to specify the incidence of Grade ≥ 2 OM in cycle 1. • The secondary objectives “To evaluate the effect of palifermin on patient reported diarrhea” and “To validate the OMDQ instrument in the colon cancer patient setting” were removed. • The secondary objective “To evaluate the incidence of Grade ≥ 2 OM in cycle 2” was added. • The efficacy analysis after all subjects have completed Cycle 2 was deleted. • The majority of exploratory analysis were removed. • The analysis of all endpoints was changed to occur after the End of Treatment visit. • The clinical study report includes data up to the End of Treatment visit (6 month time point). As a result, Kaplan-Meier estimates of 6 month progression rates were replaced with summaries of observed rates. The first long term follow-up (LTFU) visit for this study was at year 1 (month 12), and then annually thereafter, thus the time delay, while awaiting LTFU data, has been removed. • The frequency of DMC meetings was changed so that the LTFU review follows evaluation of all palifermin solid tumor studies. The DMC were in agreement that the reduction in frequency of data reviewed would not have a significant impact on the assessment of safety in this patient population. As a result, DMC and Amgen reviews were aligned across the palifermin solid tumor program. | ||
Interruptions (globally) | |||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats | |||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||