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| Name | Class |
|---|---|
| Amgen | INDUSTRY |
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Oral Mucositis associated with adjuvant radiation and concurrent chemotherapy in postoperative Head and Neck setting
This study consisted of 2 phases. The acute oral mucositis (OM) evaluation phase includes the time from randomization to the time of severe OM (WHO Grade 3 or 4) resolution (up to Week 12 or up to Week 15 for participants whose severe OM is not resolved at Week 12). In the acute OM evaluation phase, participants were randomized to receive either a single IV bolus dose of palifermin or placebo at 120 μg/kg, 3 days before the start of radiotherapy, plus 7 once-weekly palifermin or placebo doses at the same dose level during a 7-week radio/chemotherapy course. In the long-term follow up phase, participants are followed until death, withdrawal of consent, or loss to follow-up. The long-term follow up phase is still ongoing.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43. |
|
| Palifermin | Experimental | Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Administered by intravenous (IV) bolus injection |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | An adverse event is an undesirable medical occurrence (sign, symptom, or diagnosis) or worsening of a pre-existing medical condition occurring after start of study drug up to the end of acute oral mucositis (OM) evaluation phase, whether or not considered to be study drug related. If severe OM was not resolved by Week 12, AEs were documented until resolution of severe OM or Week 15, whichever occurred first. A serious AE is any event that is fatal, life threatening, requires or prolongs hospitalization, is a persistent or significant disability/incapacity or is a congenital anomaly/birth defect. The intensity of AEs was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3 based on the following: Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, Grade 4 = Life-threatening or disabling AE, Grade 5 = Death related to AE. A Protocol-specific Limiting Toxicity (PSLT) is any non-hematologic Grade 3 or 4 AE considered related to study drug. | Up to Week 12 (or Week 15 for participants with severe OM was not resolved by Week 12) |
| Ratio of Ki67-positive Cells Before and After Palifermin Treatment | The effect of palifermin on cell proliferation was to be assayed by staining for the cell cycle proliferation marker Ki67 in buccal mucosal biopsy samples taken prior to the first dose and either 24 or 48 hours after the first dose. Due to the small sample size, this analysis was not performed. | Day -3 predose and 24 or 48 hours post-dose |
| Pharmacokinetics of Palifermin | Due to the small sample size this analysis was not performed. | Day -3, predose and at 2, 5, 15, 30, 60, and 90 minutes and 2, 4, 6, 8, 10, 12, 24 and 48 hours after the first dose |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Severe Oral Mucositis (OM) (Adapted RTOG/EORTC Grade ≥3) | The adapted RTOG/EORTC mucositis assessment scale as follows: Grade 0 = no change; Grade 1 = mild enanthema, mild pain; Grade 2 = patchy mucositis, moderate edema, moderate pain; Grade 3 = confluent fibrinous mucositis, massive edema, massive pain; Grade 4 = extensive ulceration, confluent necrosis, massive hemorrhage. Due to the small sample size this analysis was not performed. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
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After recruitment of 5 participants, the study was closed to further enrollment due to administrative changes at the study center (ie, departure of principal investigator) and slow enrollment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| palifermin |
| Drug |
Administered by intravenous (IV) bolus injection |
|
| Radiotherapy | Radiation | Once daily irradiation of 20 centigray (cGy)/day x 33 fractions for a total target dose of 6600 cGy (conventional radiation therapy using standard fractionation [one fraction per day]) |
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| Cisplatin | Drug | 100 mg/m^2 intravenously (IV) on days 1, 22 and 43. |
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| Assessed daily up to Week 12 (or Week 15 if severe oral mucositis not resolved ≤ adapted RTOG/EORTC Grade 2 by Week 12). |
| Patient-Reported Mouth and Throat Soreness Score | The average patient-reported mouth and throat soreness (MTS) score as reported on question 3 of the Oral Mucositis Questionnaire for Head and Neck Cancer [OMQ-HN]): "How much mouth and throat soreness did you experience in the past 24 hours?" Participants answered on a scale from 0 (no soreness) to 4 (extreme soreness). Due to the small sample size this analysis was not performed. | Assessed daily up to Week 12 (or Week 15 if severe oral mucositis not resolved ≤ adapted RTOG/EORTC Grade 2 by Week 12). |
| Number of Participants With Disease Progression by Week 12 | Disease progression was determined by clinical examination and histopathologic examination by the Investigator. | Up to Week 12 |
| Overall Survival | Deaths during long-term follow up of subject participating in the acute phase of the study receiving placebo or Palifermin. | During long-term follow-up phase, until December 2015 |
| FG001 | Palifermin | Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43. |
| BG001 | Palifermin | Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
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| 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 Participants With Adverse Events (AEs) | An adverse event is an undesirable medical occurrence (sign, symptom, or diagnosis) or worsening of a pre-existing medical condition occurring after start of study drug up to the end of acute oral mucositis (OM) evaluation phase, whether or not considered to be study drug related. If severe OM was not resolved by Week 12, AEs were documented until resolution of severe OM or Week 15, whichever occurred first. A serious AE is any event that is fatal, life threatening, requires or prolongs hospitalization, is a persistent or significant disability/incapacity or is a congenital anomaly/birth defect. The intensity of AEs was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3 based on the following: Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, Grade 4 = Life-threatening or disabling AE, Grade 5 = Death related to AE. A Protocol-specific Limiting Toxicity (PSLT) is any non-hematologic Grade 3 or 4 AE considered related to study drug. | Posted | Number | participants | Up to Week 12 (or Week 15 for participants with severe OM was not resolved by Week 12) |
|
|
| |||||||||||||||||||||||||||||||||||||
| Primary | Ratio of Ki67-positive Cells Before and After Palifermin Treatment | The effect of palifermin on cell proliferation was to be assayed by staining for the cell cycle proliferation marker Ki67 in buccal mucosal biopsy samples taken prior to the first dose and either 24 or 48 hours after the first dose. Due to the small sample size, this analysis was not performed. | Posted | Day -3 predose and 24 or 48 hours post-dose |
| |||||||||||||||||||||||||||||||||||||||||
| Primary | Pharmacokinetics of Palifermin | Due to the small sample size this analysis was not performed. | Posted | Day -3, predose and at 2, 5, 15, 30, 60, and 90 minutes and 2, 4, 6, 8, 10, 12, 24 and 48 hours after the first dose |
|
| ||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Severe Oral Mucositis (OM) (Adapted RTOG/EORTC Grade ≥3) | The adapted RTOG/EORTC mucositis assessment scale as follows: Grade 0 = no change; Grade 1 = mild enanthema, mild pain; Grade 2 = patchy mucositis, moderate edema, moderate pain; Grade 3 = confluent fibrinous mucositis, massive edema, massive pain; Grade 4 = extensive ulceration, confluent necrosis, massive hemorrhage. Due to the small sample size this analysis was not performed. | Posted | Assessed daily up to Week 12 (or Week 15 if severe oral mucositis not resolved ≤ adapted RTOG/EORTC Grade 2 by Week 12). |
| |||||||||||||||||||||||||||||||||||||||||
| Secondary | Patient-Reported Mouth and Throat Soreness Score | The average patient-reported mouth and throat soreness (MTS) score as reported on question 3 of the Oral Mucositis Questionnaire for Head and Neck Cancer [OMQ-HN]): "How much mouth and throat soreness did you experience in the past 24 hours?" Participants answered on a scale from 0 (no soreness) to 4 (extreme soreness). Due to the small sample size this analysis was not performed. | Posted | Assessed daily up to Week 12 (or Week 15 if severe oral mucositis not resolved ≤ adapted RTOG/EORTC Grade 2 by Week 12). |
| |||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Disease Progression by Week 12 | Disease progression was determined by clinical examination and histopathologic examination by the Investigator. | Tumor response data was missing for one participant. | Posted | Number | participants | Up to Week 12 |
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Overall Survival | Deaths during long-term follow up of subject participating in the acute phase of the study receiving placebo or Palifermin. | Subjects who received placebo duringthe acute phase of the study. | Posted | Count of Participants | Participants | During long-term follow-up phase, until December 2015 |
|
|
Up to 15 weeks from first dose of IP
The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
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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 | Placebo | Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of matching placebo. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of matching placebo after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43. | 0 | 2 | 2 | 2 | ||
| EG001 | Palifermin | Three days before the start of radiotherapy (Day -3), participants received a single intravenous (IV) bolus injection of palifermin at 120 μg/kg. During radiotherapy (beginning on Day 1), participants received a weekly single IV bolus injection of palifermin at 120 μg/kg after the last radiation fraction of that week (usually on Fridays) until grade ≥3 oral mucositis occurred, or for a maximum 8 doses (completion of radiotherapy). Participants also received cisplatin 100 mg/m^2 on days 1, 22 and 43. | 2 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 9.0 | Systematic Assessment |
| |
| Multi-organ failure | General disorders | MedDRA 9.0 | Systematic Assessment |
| |
| Peritonitis bacterial | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
| |
| Staphylococcal sepsis | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 9.0 | Systematic Assessment |
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| C-reactive protein increased | Investigations | MedDRA 9.0 | Systematic Assessment |
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| Red blood cell count increased | Investigations | MedDRA 9.0 | Systematic Assessment |
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| White blood cell count increased | Investigations | MedDRA 9.0 | Systematic Assessment |
| |
| Gum neoplasm malignant stage unspecified | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 9.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 9.0 | Systematic Assessment |
| |
| Lymphadenitis | Blood and lymphatic system disorders | MedDRA 9.0 | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
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| Dysphagia | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
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| Oral pain | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
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| Salivary hypersecretion | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
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| Facial pain | General disorders | MedDRA 9.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 9.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 9.0 | Systematic Assessment |
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| Bacteriuria | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 9.0 | Systematic Assessment |
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| Body temperature increased | Investigations | MedDRA 9.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 9.0 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
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| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
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| Lymphoedema | Vascular disorders | MedDRA 9.0 | Systematic Assessment |
|
Pharmacokinetic, pharmacodynamic, safety and efficacy endpoints were not evaluable due to the limited number of subjects enrolled.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits sponsor a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Sponsor may remove confidential information, but authors have final control and approval of publication content. For multi-center studies, investigator agrees not to publish any results before the first multi-center publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Hans Olivecrona, MD PhD | Biovitrum | +46 8 697 20 00 | hans.olivecrona@sobi.com |
| ID | Term |
|---|---|
| D052016 | Mucositis |
| D006258 | Head and Neck Neoplasms |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
| D009371 | Neoplasms by Site |
Not provided
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| ID | Term |
|---|---|
| D051523 | Fibroblast Growth Factor 7 |
| D011878 | Radiotherapy |
| D002945 | Cisplatin |
| ID | Term |
|---|---|
| D005346 | Fibroblast Growth Factors |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D013812 | Therapeutics |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
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| Male |
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| Severe AE (Grade 3, 4 or 5) |
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| Treatment related adverse event |
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| Treatment related serious AE |
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| Treatment related severe AE (Grade 3, 4 or 5) |
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| Study Discontinuation Due to AE |
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| Protocol Specific Limiting Toxicity (PSLT) |
|
| Deaths |
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| Units | Counts |
|---|---|
| Participants |
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| Counts |
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| Participants |
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| Units | Counts |
|---|---|
| Participants |
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