Study to Evaluate Palifermin in the Reduction of Dysphagia in Patients With Locally Advanced Non-Small Cell Lung Cancer (NSCLC)
Study Details
Study Description
Brief Summary
The purpose of this study is to determine if palifermin will reduce the incidence of dysphagia in patients receiving concurrent chemoradiotherapy followed by consolidation chemotherapy for treatment of unresectable stage III Non-Small Cell Lung Cancer (NSCLC).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
During the acute dysphagia evaluation phase (the period lasting from the administration of the first dose of investigational product through Week 12 (or up to Week 16 if dysphagia is not resolved to CTCAE v3.0 grade ≤ 1 by Week 12) participants underwent acute dysphagia assessments twice weekly. All participants were followed for disease progression, second primary tumors, other malignancies, and overall survival until death or loss to follow-up during the long term follow-up (still ongoing).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. Concurrent radio/chemotherapy was given as follows: standard radiotherapy 2 Gy once daily x 30 to 33 fractions (6 to 7 weeks) for a total target dose of 60 to 66 Gy paclitaxel 50 mg/m^2 intravenous (IV) infusion on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy) carboplatin dosed at an area under the curve (AUC) 2.0 IV on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy). Participants subsequently received two 21-day cycles of consolidation chemotherapy with paclitaxel 225 mg/m^2 and carboplatin dosed at AUC 6.0. |
Drug: Placebo
Radiation: Radiotherapy
Drug: Paclitaxel
Drug: Carboplatin
|
| Experimental: Palifermin Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. Concurrent radio/chemotherapy (administered for 6 to 7 weeks) was given as follows: standard radiotherapy 2 Gy once daily x 30 to 33 fractions (6 to 7 weeks) for a total target dose of 60 to 66 Gy paclitaxel 50 mg/m^2 IV infusion on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy) carboplatin dosed at an area under the curve (AUC) 2.0 IV on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy). Participants subsequently received two 21-day cycles of consolidation chemotherapy with paclitaxel 225 mg/m^2 and carboplatin dosed at AUC 6.0. |
Drug: Palifermin
Other Names:
Radiation: Radiotherapy
Drug: Paclitaxel
Drug: Carboplatin
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Grade 2 or Higher Dysphagia [Start of treatment through Week 16]
Participants underwent acute dysphagia assessments twice weekly during Weeks 1 through 7, and twice weekly thereafter (Weeks 8 through 12) and once weekly after Week 12 until dysphagia resolved to grade ≤ 1 but not beyond Week 16. Dysphagia (difficulty swallowing) was graded using the Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) dysphagia scale according to the following: Grade 1: Symptomatic, able to eat regular diet; Grade 2: Symptomatic and altered eating/swallowing (e.g., altered dietary habits, oral supplements), IV fluids indicated <24 hours; Grade 3: Symptomatic and severely altered eating/swallowing (e.g., inadequate oral caloric or fluid intake), IV fluids, tube feedings, or total parenteral nutrition (TPN) indicated ≥24 hours; Grade 4: Life-threatening consequences (e.g., obstruction, perforation).
Secondary Outcome Measures
- Duration of Grade 2 or Higher Dysphagia [Start of treatment through Week 16]
Duration of grade 2 or higher dysphagia was calculated in days from the onset (first occurrence of grade ≥ 2) to the resolution (grade ≤ 1 after the last grade ≥ 2) of dysphagia. Participants with no assessments were assumed as having grade ≥ 2 dysphagia and with a duration of the mean duration of all participants.
- Maximal Dysphagia Grade [Start of treatment through Week 16]
The mean maximal grade of dysphagia for each participant during the study. Dysphagia (difficulty swallowing) was graded using the Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) dysphagia scale according to the following: Grade 1: Symptomatic, able to eat regular diet; Grade 2: Symptomatic and altered eating/swallowing (e.g., altered dietary habits, oral supplements), IV fluids indicated <24 hours; Grade 3: Symptomatic and severely altered eating/swallowing (e.g., inadequate oral caloric or fluid intake), IV fluids, tube feedings, or total parenteral nutrition (TPN) indicated ≥24 hours; Grade 4: Life-threatening consequences (e.g., obstruction, perforation).
- Number of Participants With Severe (Grade 3 or Higher) Dysphagia [Start of treatment through Week 16]
Participants underwent acute dysphagia assessments twice weekly during Weeks 1 through 7, and twice weekly thereafter (Weeks 8 through 12) and once weekly after Week 12 until dysphagia resolved to grade ≤ 1 but not beyond Week 16. Dysphagia (difficulty swallowing) was graded using the Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) dysphagia scale according to the following: Grade 1: Symptomatic, able to eat regular diet; Grade 2: Symptomatic and altered eating/swallowing (e.g., altered dietary habits, oral supplements), IV fluids indicated <24 hours; Grade 3: Symptomatic and severely altered eating/swallowing (e.g., inadequate oral caloric or fluid intake), IV fluids, tube feedings, or total parenteral nutrition (TPN) indicated ≥24 hours; Grade 4: Life-threatening consequences (e.g., obstruction, perforation).
- Number of Participants With Unplanned Breaks in Radiotherapy [Week 1 to Week 6]
The number of participants with unplanned breaks in radiotherapy of ≥ 5 days or who discontinued radiotherapy during Week 1 to Week 6.
- Maximal Eastern Cooperative Oncology Group (ECOG) Performance Status Increase [Baseline through Week 12]
Maximal increase from Baseline in Eastern Cooperative Oncology Group (ECOG) performance status. ECOG is a scale to assess how a patient's disease is progressing, how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; Grade 2: Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair; Grade 5: Dead.
- Number of Participants Hospitalized [Baseline to Week 16]
- Maximal Body Weight Loss [Baseline through Week 12]
Maximal weight loss observed from Baseline through to Week 12.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients with a histologically or cytologically proven diagnosis of NSCLC
-
Unresectable (locally advanced) stage IIIa or IIIb disease
-
Initial radiotherapy field of treatment to encompass greater than or equal to 30% of the esophagus
-
Life expectancy greater than or equal to 6 months
-
Estimated weight loss less than or equal to 10% in the 3 months before study randomization
-
Measurable disease
-
18 years of age or older
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
-
Hemoglobin (hgb) greater than or equal to 10 g/dL without transfusional support or growth factor use in the 4 weeks before study randomization
-
Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L without growth factor use in the 2 weeks before study randomization
-
Platelet count greater than or equal to 100 x 10^9/L
-
Serum bilirubin less than or equal to 1.5 x institutional upper limit of normal (ULN)
-
Serum creatinine less than or equal to 2.0 mg/dL (Note: Patients with a serum creatinine greater than or equal to 1.4 and less than or equal to 2.0 mg/dL must demonstrate a 24-hour urinary creatinine clearance greater than or equal to 50 mL/min)
-
Females of childbearing potential: negative serum or urine pregnancy test
-
Patient must give written informed consent before participating in any study-specific procedure, randomization, or receiving investigational product.
-
Patients with reproductive capability must agree to practice adequate contraception methods.
Exclusion Criteria:
-
Metastatic disease (M1)/stage 4 NSCLC
-
Pleural or pericardial effusion greater than 100 ml in volume as documented by appropriate imaging (positron emission tomography [PET], computed tomography [CT] scan or ultrasound). If an effusion greater than 100 ml is documented by cytology to be free from malignancy and the investigator feels the patient is capable of receiving chemo/radiotherapy for their primary disease/ NSCLC, the investigator should discuss the patient with the study physician at Amgen. Effusions smaller than 100 ml would be acceptable, unless the investigator suspects that the effusion is malignant, in which case the effusions should be evaluated by cytology. Sponsor approval must be obtained before patient is randomized.
-
Plan to remove the tumor surgically before completing the protocol chemo/radiotherapy course
-
Shielding of any part of the esophagus during radiotherapy (including posterior spinal cord shielding)
-
Prior chemotherapy, radiotherapy, or surgery for NSCLC
-
Prior invasive malignancy during the past 3 years other than non-melanomatous skin cancer. Note: Patients with prior surgically-cured malignancies [eg, stage I breast cancer or prostate cancer, in-situ carcinoma of the cervix, etc] are not excluded; however, sponsor approval must be obtained before patient is randomized.
-
Presence or history of dysphagia or conditions predisposing to dysphagia (eg, uncontrolled gastroesophageal reflux disease [GERD], dyspepsia, etc)
-
History of pancreatitis
-
Four weeks or less since completion of treatment using an investigational product/device in another clinical study or presence of any unresolved toxicity from previous treatment
-
Previous treatment on this study or with a fibroblast growth factor
-
Known to be sero-positive for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV)
-
Pregnant or breastfeeding women
-
Known sensitivity to E. coli derived products
-
Compromised ability of the patient to give written informed consent and/or to comply with study procedures
-
Refusal to sign an informed consent form to participate in this study, and sign the hospital information release form, if applicable
-
Unwilling or unable to complete the patient reported outcome (PRO) questionnaires
-
Psychological, social, familial, or geographical reasons that would prevent regular follow-up
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Swedish Orphan Biovitrum
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 20030185
Study Results
Participant Flow
| Recruitment Details | This study was conducted from 06 January 2005 until 20 December 2007 (last participant's last visit for the acute dysphagia evaluation phase). At the time of this report, the long-term safety follow-up period is ongoing. |
|---|---|
| Pre-assignment Detail | 100 patients were initially enrolled at 25 sites, however, data from one site could not be used and is excluded from this results analysis. |
| Arm/Group Title | Placebo | Palifermin |
|---|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, for a total of 7 doses. Concurrent radio/chemotherapy was given as follows: standard radiotherapy 2 Gy once daily x 30 to 33 fractions (6 to 7 weeks) for a total target dose of 60 to 66 Gy paclitaxel 50 mg/m^2 intravenous (IV) infusion on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy) carboplatin dosed at an area under the curve (AUC) 2.0 IV on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy). Participants subsequently received two 21-day cycles of consolidation chemotherapy with paclitaxel 225 mg/m^2 and carboplatin dosed at AUC 6.0. | Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. Concurrent radio/chemotherapy (administered for 6 to 7 weeks) was given as follows: standard radiotherapy 2 Gy once daily x 30 to 33 fractions (6 to 7 weeks) for a total target dose of 60 to 66 Gy paclitaxel 50 mg/m^2 IV infusion on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy) carboplatin dosed at an area under the curve (AUC) 2.0 IV on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy). Participants subsequently received two 21-day cycles of consolidation chemotherapy with paclitaxel 225 mg/m^2 and carboplatin dosed at AUC 6.0. |
| Period Title: Overall Study | ||
| STARTED | 46 | 49 |
| Participants Treated | 46 | 48 |
| COMPLETED | 28 | 40 |
| NOT COMPLETED | 18 | 9 |
Baseline Characteristics
| Arm/Group Title | Placebo | Palifermin | Total |
|---|---|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. | Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. | Total of all reporting groups |
| Overall Participants | 46 | 49 | 95 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
64.2
(7.7)
|
61.6
(9.8)
|
62.9
(8.9)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
14
30.4%
|
15
30.6%
|
29
30.5%
|
| Male |
32
69.6%
|
34
69.4%
|
66
69.5%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| White or Causcasian |
43
93.5%
|
43
87.8%
|
86
90.5%
|
| Black or African-American |
2
4.3%
|
2
4.1%
|
4
4.2%
|
| Hispanic or Latino |
1
2.2%
|
1
2%
|
2
2.1%
|
| Asian |
0
0%
|
1
2%
|
1
1.1%
|
| Japanese |
0
0%
|
1
2%
|
1
1.1%
|
| Other |
0
0%
|
1
2%
|
1
1.1%
|
| Disease Stage (participants) [Number] | |||
| Stage 3A |
14
30.4%
|
19
38.8%
|
33
34.7%
|
| Stage 3B |
32
69.6%
|
30
61.2%
|
62
65.3%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number] | |||
| Grade 0 |
21
45.7%
|
21
42.9%
|
42
44.2%
|
| Grade 1 |
23
50%
|
26
53.1%
|
49
51.6%
|
| Grade 2 |
2
4.3%
|
2
4.1%
|
4
4.2%
|
| Weight Loss Over Last 3 Months (participants) [Number] | |||
| < 5% |
35
76.1%
|
37
75.5%
|
72
75.8%
|
| 5 - 10% |
11
23.9%
|
12
24.5%
|
23
24.2%
|
| Randomization Strata (participants) [Number] | |||
| 3A, 0-1, <5% |
10
21.7%
|
11
22.4%
|
21
22.1%
|
| 3A, 0-1, 5-10% |
4
8.7%
|
6
12.2%
|
10
10.5%
|
| 3A, 2, <5% |
1
2.2%
|
2
4.1%
|
3
3.2%
|
| 3A, 2, 5-10% |
1
2.2%
|
0
0%
|
1
1.1%
|
| 3B, 0-1, <5% |
24
52.2%
|
25
51%
|
49
51.6%
|
| 3B, 0-1, 5-10% |
6
13%
|
5
10.2%
|
11
11.6%
|
| 3B, 2, <5% |
0
0%
|
0
0%
|
0
0%
|
| 3B, 2, 5-10% |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Number of Participants With Grade 2 or Higher Dysphagia |
|---|---|
| Description | Participants underwent acute dysphagia assessments twice weekly during Weeks 1 through 7, and twice weekly thereafter (Weeks 8 through 12) and once weekly after Week 12 until dysphagia resolved to grade ≤ 1 but not beyond Week 16. Dysphagia (difficulty swallowing) was graded using the Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) dysphagia scale according to the following: Grade 1: Symptomatic, able to eat regular diet; Grade 2: Symptomatic and altered eating/swallowing (e.g., altered dietary habits, oral supplements), IV fluids indicated <24 hours; Grade 3: Symptomatic and severely altered eating/swallowing (e.g., inadequate oral caloric or fluid intake), IV fluids, tube feedings, or total parenteral nutrition (TPN) indicated ≥24 hours; Grade 4: Life-threatening consequences (e.g., obstruction, perforation). |
| Time Frame | Start of treatment through Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Placebo | Palifermin |
|---|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. | Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. |
| Measure Participants | 46 | 49 |
| Yes |
32
69.6%
|
30
61.2%
|
| No |
13
28.3%
|
18
36.7%
|
| No assessment |
1
2.2%
|
1
2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Palifermin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3550 |
| Comments | Generalized Cochran-Mantel-Haenszel test for general association. Participants with no assessments were assumed as having grade ≥ 2 dysphagia in hypothesis testing. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by disease stage, ECOG performance status, and estimated weight loss in the 3 months before study randomization. | |
| Method of Estimation | Estimation Parameter | Chi-Square Statistic |
| Estimated Value | 0.8553 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Duration of Grade 2 or Higher Dysphagia |
|---|---|
| Description | Duration of grade 2 or higher dysphagia was calculated in days from the onset (first occurrence of grade ≥ 2) to the resolution (grade ≤ 1 after the last grade ≥ 2) of dysphagia. Participants with no assessments were assumed as having grade ≥ 2 dysphagia and with a duration of the mean duration of all participants. |
| Time Frame | Start of treatment through Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Placebo | Palifermin |
|---|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. | Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. |
| Measure Participants | 46 | 49 |
| Mean (Standard Deviation) [days] |
32.4
(30.1)
|
25.3
(28.0)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Palifermin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3189 |
| Comments | Generalized Cochran-Mantel-Haenszel test for mean score difference using modified ridit score. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by disease stage, ECOG performance status, and estimated weight loss in the 3 months before study randomization. | |
| Method of Estimation | Estimation Parameter | Chi-Square Statistic |
| Estimated Value | 0.9936 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maximal Dysphagia Grade |
|---|---|
| Description | The mean maximal grade of dysphagia for each participant during the study. Dysphagia (difficulty swallowing) was graded using the Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) dysphagia scale according to the following: Grade 1: Symptomatic, able to eat regular diet; Grade 2: Symptomatic and altered eating/swallowing (e.g., altered dietary habits, oral supplements), IV fluids indicated <24 hours; Grade 3: Symptomatic and severely altered eating/swallowing (e.g., inadequate oral caloric or fluid intake), IV fluids, tube feedings, or total parenteral nutrition (TPN) indicated ≥24 hours; Grade 4: Life-threatening consequences (e.g., obstruction, perforation). |
| Time Frame | Start of treatment through Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set participants with dysphagia assessments. |
| Arm/Group Title | Placebo | Palifermin |
|---|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. | Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. |
| Measure Participants | 45 | 48 |
| Mean (Standard Deviation) [grade] |
1.9
(1.0)
|
1.8
(0.9)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Palifermin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5086 |
| Comments | Generalized Cochran-Mantel-Haenszel test for general association. Participants with no assessments were assumed as having grade 5 dysphagia in hypothesis testing. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by disease stage, ECOG performance status, and estimated weight loss in the 3 months before study randomization. | |
| Method of Estimation | Estimation Parameter | Chi-Square Statistic |
| Estimated Value | 0.4370 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Severe (Grade 3 or Higher) Dysphagia |
|---|---|
| Description | Participants underwent acute dysphagia assessments twice weekly during Weeks 1 through 7, and twice weekly thereafter (Weeks 8 through 12) and once weekly after Week 12 until dysphagia resolved to grade ≤ 1 but not beyond Week 16. Dysphagia (difficulty swallowing) was graded using the Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) dysphagia scale according to the following: Grade 1: Symptomatic, able to eat regular diet; Grade 2: Symptomatic and altered eating/swallowing (e.g., altered dietary habits, oral supplements), IV fluids indicated <24 hours; Grade 3: Symptomatic and severely altered eating/swallowing (e.g., inadequate oral caloric or fluid intake), IV fluids, tube feedings, or total parenteral nutrition (TPN) indicated ≥24 hours; Grade 4: Life-threatening consequences (e.g., obstruction, perforation). |
| Time Frame | Start of treatment through Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Placebo | Palifermin |
|---|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. | Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. |
| Measure Participants | 46 | 49 |
| Yes |
13
28.3%
|
11
22.4%
|
| No |
32
69.6%
|
37
75.5%
|
| No assessment |
1
2.2%
|
1
2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Palifermin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4976 |
| Comments | Generalized Cochran-Mantel-Haenszel test for general association. Participants with no assessments were assumed as having grade ≥ 3 dysphagia in hypothesis testing. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by disease stage, ECOG performance status, and estimated weight loss in the 3 months before study randomization. | |
| Method of Estimation | Estimation Parameter | Chi-Square Statistic |
| Estimated Value | 0.4600 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Unplanned Breaks in Radiotherapy |
|---|---|
| Description | The number of participants with unplanned breaks in radiotherapy of ≥ 5 days or who discontinued radiotherapy during Week 1 to Week 6. |
| Time Frame | Week 1 to Week 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Placebo | Palifermin |
|---|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. | Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. |
| Measure Participants | 46 | 49 |
| Yes |
15
32.6%
|
9
18.4%
|
| No |
29
63%
|
38
77.6%
|
| Did not receive radiotherapy |
2
4.3%
|
2
4.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Palifermin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1115 |
| Comments | Generalized Cochran-Mantel-Haenszel test for general association. Participants who never received radiotherapy were assumed to have unplanned breaks. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by disease stage, ECOG performance status, and estimated weight loss in the 3 months before study randomization. | |
| Method of Estimation | Estimation Parameter | Chi-Square Statistic |
| Estimated Value | -2.5325 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maximal Eastern Cooperative Oncology Group (ECOG) Performance Status Increase |
|---|---|
| Description | Maximal increase from Baseline in Eastern Cooperative Oncology Group (ECOG) performance status. ECOG is a scale to assess how a patient's disease is progressing, how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; Grade 2: Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair; Grade 5: Dead. |
| Time Frame | Baseline through Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set participants with available ECOG data |
| Arm/Group Title | Placebo | Palifermin |
|---|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. | Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. |
| Measure Participants | 44 | 46 |
| Mean (Standard Deviation) [units on a scale] |
1.5
(1.3)
|
0.9
(1.1)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Palifermin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0621 |
| Comments | Generalized Cochran-Mantel-Haenszel (CMH) test for mean score difference using modified ridit score. Participants without any ECOG assessment post baseline were assumed to have ECOG status of 5 in the CMH test. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by disease stage, ECOG performance status, and estimated weight loss in the 3 months before study randomization. | |
| Method of Estimation | Estimation Parameter | Chi-Square Statistic |
| Estimated Value | 3.4812 | |
| Confidence Interval |
(2-Sided) % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants Hospitalized |
|---|---|
| Description | |
| Time Frame | Baseline to Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Placebo | Palifermin |
|---|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. | Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. |
| Measure Participants | 46 | 49 |
| Hospitalized |
31
67.4%
|
34
69.4%
|
| Not hospitalized |
15
32.6%
|
15
30.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8639 |
| Comments | Generalized Cochran-Mantel-Haenszel test for general association. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by disease stage, ECOG performance status, and estimated weight loss in the 3 months before study randomization. | |
| Method of Estimation | Estimation Parameter | Chi-Square Statistic |
| Estimated Value | 0.0294 | |
| Confidence Interval |
() 95% to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Maximal Body Weight Loss |
|---|---|
| Description | Maximal weight loss observed from Baseline through to Week 12. |
| Time Frame | Baseline through Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set with available data |
| Arm/Group Title | Placebo | Palifermin |
|---|---|---|
| Arm/Group Description | Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. | Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. |
| Measure Participants | 42 | 45 |
| Mean (Standard Deviation) [kilograms] |
4.63
(4.13)
|
5.44
(4.33)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Palifermin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1996 |
| Comments | Generalized Cochran-Mantel-Haenszel test for mean score difference using modified ridit score. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by disease stage, ECOG performance status, and estimated weight loss in the 3 months before study randomization. | |
| Method of Estimation | Estimation Parameter | Chi-Square Statistic |
| Estimated Value | 3.1414 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | From baseline up to Week 12 | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. | |||
| Arm/Group Title | Placebo | Palifermin | ||
| Arm/Group Description | Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. | Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. | ||
All Cause Mortality |
||||
| Placebo | Palifermin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Placebo | Palifermin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 30/46 (65.2%) | 21/48 (43.8%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 5/46 (10.9%) | 7/48 (14.6%) | ||
| Leukopenia | 1/46 (2.2%) | 1/48 (2.1%) | ||
| Neutropenia | 3/46 (6.5%) | 4/48 (8.3%) | ||
| Pancytopenia | 2/46 (4.3%) | 1/48 (2.1%) | ||
| Thrombocytopenia | 1/46 (2.2%) | 1/48 (2.1%) | ||
| Cardiac disorders | ||||
| Acute coronary syndrome | 1/46 (2.2%) | 0/48 (0%) | ||
| Acute myocardial infarction | 2/46 (4.3%) | 0/48 (0%) | ||
| Arrhythmia | 1/46 (2.2%) | 0/48 (0%) | ||
| Atrial fibrillation | 2/46 (4.3%) | 1/48 (2.1%) | ||
| Cardiac failure congestive | 2/46 (4.3%) | 0/48 (0%) | ||
| Tachycardia | 2/46 (4.3%) | 0/48 (0%) | ||
| Eye disorders | ||||
| Vision blurred | 1/46 (2.2%) | 0/48 (0%) | ||
| Gastrointestinal disorders | ||||
| Colitis | 1/46 (2.2%) | 0/48 (0%) | ||
| Colonic pseudo-obstruction | 1/46 (2.2%) | 0/48 (0%) | ||
| Diarrhoea | 0/46 (0%) | 1/48 (2.1%) | ||
| Dysphagia | 2/46 (4.3%) | 4/48 (8.3%) | ||
| Gastrointestinal hypomotility | 0/46 (0%) | 1/48 (2.1%) | ||
| Nausea | 3/46 (6.5%) | 3/48 (6.3%) | ||
| Odynophagia | 1/46 (2.2%) | 0/48 (0%) | ||
| Oesophagitis | 4/46 (8.7%) | 0/48 (0%) | ||
| Stomatitis | 0/46 (0%) | 1/48 (2.1%) | ||
| Vomiting | 2/46 (4.3%) | 1/48 (2.1%) | ||
| General disorders | ||||
| Asthenia | 0/46 (0%) | 2/48 (4.2%) | ||
| Chest discomfort | 1/46 (2.2%) | 0/48 (0%) | ||
| Death | 1/46 (2.2%) | 0/48 (0%) | ||
| Disease progression | 0/46 (0%) | 1/48 (2.1%) | ||
| Fatigue | 0/46 (0%) | 1/48 (2.1%) | ||
| General physical health deterioration | 1/46 (2.2%) | 1/48 (2.1%) | ||
| Mucosal inflammation | 0/46 (0%) | 1/48 (2.1%) | ||
| Performance status decreased | 1/46 (2.2%) | 0/48 (0%) | ||
| Pyrexia | 2/46 (4.3%) | 1/48 (2.1%) | ||
| Infections and infestations | ||||
| Cellulitis | 1/46 (2.2%) | 1/48 (2.1%) | ||
| Pneumonia | 2/46 (4.3%) | 1/48 (2.1%) | ||
| Respiratory moniliasis | 0/46 (0%) | 1/48 (2.1%) | ||
| Respiratory tract infection | 1/46 (2.2%) | 1/48 (2.1%) | ||
| Sepsis | 1/46 (2.2%) | 1/48 (2.1%) | ||
| Septic shock | 0/46 (0%) | 1/48 (2.1%) | ||
| Urinary tract infection | 1/46 (2.2%) | 0/48 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Radiation oesophagitis | 2/46 (4.3%) | 1/48 (2.1%) | ||
| Tracheal obstruction | 1/46 (2.2%) | 0/48 (0%) | ||
| Vascular graft occlusion | 1/46 (2.2%) | 0/48 (0%) | ||
| Investigations | ||||
| Weight decreased | 0/46 (0%) | 1/48 (2.1%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 0/46 (0%) | 1/48 (2.1%) | ||
| Dehydration | 4/46 (8.7%) | 1/48 (2.1%) | ||
| Hypocalcaemia | 0/46 (0%) | 1/48 (2.1%) | ||
| Hypokalaemia | 0/46 (0%) | 1/48 (2.1%) | ||
| Hypomagnesaemia | 0/46 (0%) | 1/48 (2.1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 0/46 (0%) | 1/48 (2.1%) | ||
| Myalgia | 0/46 (0%) | 1/48 (2.1%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Neoplasm progression | 1/46 (2.2%) | 0/48 (0%) | ||
| Non-small cell lung cancer | 0/46 (0%) | 1/48 (2.1%) | ||
| Nervous system disorders | ||||
| Dizziness | 2/46 (4.3%) | 1/48 (2.1%) | ||
| Hypoaesthesia | 0/46 (0%) | 1/48 (2.1%) | ||
| Syncope | 0/46 (0%) | 1/48 (2.1%) | ||
| Psychiatric disorders | ||||
| Alcohol withdrawal syndrome | 1/46 (2.2%) | 0/48 (0%) | ||
| Confusional state | 1/46 (2.2%) | 0/48 (0%) | ||
| Renal and urinary disorders | ||||
| Acute prerenal failure | 1/46 (2.2%) | 0/48 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Bronchial obstruction | 1/46 (2.2%) | 0/48 (0%) | ||
| Chronic obstructive pulmonary disease | 1/46 (2.2%) | 0/48 (0%) | ||
| Cough | 0/46 (0%) | 1/48 (2.1%) | ||
| Dyspnoea | 2/46 (4.3%) | 1/48 (2.1%) | ||
| Epistaxis | 0/46 (0%) | 1/48 (2.1%) | ||
| Haemoptysis | 1/46 (2.2%) | 0/48 (0%) | ||
| Hypoxia | 1/46 (2.2%) | 1/48 (2.1%) | ||
| Pleural effusion | 1/46 (2.2%) | 0/48 (0%) | ||
| Pulmonary embolism | 1/46 (2.2%) | 1/48 (2.1%) | ||
| Respiratory failure | 1/46 (2.2%) | 0/48 (0%) | ||
| Vascular disorders | ||||
| Circulatory collapse | 1/46 (2.2%) | 0/48 (0%) | ||
| Deep vein thrombosis | 0/46 (0%) | 1/48 (2.1%) | ||
| Embolism | 1/46 (2.2%) | 0/48 (0%) | ||
| Hypotension | 2/46 (4.3%) | 0/48 (0%) | ||
| Thrombosis | 0/46 (0%) | 1/48 (2.1%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Palifermin | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 45/46 (97.8%) | 48/48 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 21/46 (45.7%) | 27/48 (56.3%) | ||
| Leukopenia | 8/46 (17.4%) | 18/48 (37.5%) | ||
| Neutropenia | 11/46 (23.9%) | 13/48 (27.1%) | ||
| Thrombocytopenia | 5/46 (10.9%) | 10/48 (20.8%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 4/46 (8.7%) | 3/48 (6.3%) | ||
| Constipation | 13/46 (28.3%) | 14/48 (29.2%) | ||
| Diarrhoea | 9/46 (19.6%) | 9/48 (18.8%) | ||
| Dry mouth | 1/46 (2.2%) | 4/48 (8.3%) | ||
| Dyspepsia | 7/46 (15.2%) | 8/48 (16.7%) | ||
| Nausea | 23/46 (50%) | 25/48 (52.1%) | ||
| Oesophagitis | 1/46 (2.2%) | 4/48 (8.3%) | ||
| Vomiting | 11/46 (23.9%) | 10/48 (20.8%) | ||
| General disorders | ||||
| Asthenia | 5/46 (10.9%) | 9/48 (18.8%) | ||
| Chest pain | 4/46 (8.7%) | 7/48 (14.6%) | ||
| Fatigue | 14/46 (30.4%) | 19/48 (39.6%) | ||
| Non-cardiac chest pain | 0/46 (0%) | 3/48 (6.3%) | ||
| Oedema peripheral | 4/46 (8.7%) | 2/48 (4.2%) | ||
| Pain | 3/46 (6.5%) | 2/48 (4.2%) | ||
| Pyrexia | 9/46 (19.6%) | 8/48 (16.7%) | ||
| Infections and infestations | ||||
| Pneumonia | 1/46 (2.2%) | 5/48 (10.4%) | ||
| Injury, poisoning and procedural complications | ||||
| Radiation skin injury | 6/46 (13%) | 10/48 (20.8%) | ||
| Investigations | ||||
| Weight decreased | 7/46 (15.2%) | 6/48 (12.5%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 8/46 (17.4%) | 13/48 (27.1%) | ||
| Dehydration | 6/46 (13%) | 10/48 (20.8%) | ||
| Hypocalcaemia | 3/46 (6.5%) | 3/48 (6.3%) | ||
| Hypokalaemia | 8/46 (17.4%) | 8/48 (16.7%) | ||
| Hypomagnesaemia | 1/46 (2.2%) | 3/48 (6.3%) | ||
| Hyponatraemia | 3/46 (6.5%) | 0/48 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 3/46 (6.5%) | 3/48 (6.3%) | ||
| Back pain | 5/46 (10.9%) | 5/48 (10.4%) | ||
| Musculoskeletal chest pain | 3/46 (6.5%) | 1/48 (2.1%) | ||
| Musculoskeletal pain | 1/46 (2.2%) | 3/48 (6.3%) | ||
| Myalgia | 5/46 (10.9%) | 6/48 (12.5%) | ||
| Neck pain | 3/46 (6.5%) | 1/48 (2.1%) | ||
| Nervous system disorders | ||||
| Dizziness | 5/46 (10.9%) | 6/48 (12.5%) | ||
| Dysgeusia | 3/46 (6.5%) | 8/48 (16.7%) | ||
| Headache | 3/46 (6.5%) | 4/48 (8.3%) | ||
| Hypoaesthesia | 3/46 (6.5%) | 0/48 (0%) | ||
| Neuropathy peripheral | 0/46 (0%) | 4/48 (8.3%) | ||
| Paraesthesia | 2/46 (4.3%) | 3/48 (6.3%) | ||
| Peripheral sensory neuropathy | 3/46 (6.5%) | 4/48 (8.3%) | ||
| Psychiatric disorders | ||||
| Anxiety | 6/46 (13%) | 3/48 (6.3%) | ||
| Depression | 4/46 (8.7%) | 2/48 (4.2%) | ||
| Insomnia | 9/46 (19.6%) | 8/48 (16.7%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 12/46 (26.1%) | 19/48 (39.6%) | ||
| Dysphonia | 3/46 (6.5%) | 9/48 (18.8%) | ||
| Dyspnoea | 8/46 (17.4%) | 12/48 (25%) | ||
| Epistaxis | 4/46 (8.7%) | 6/48 (12.5%) | ||
| Haemoptysis | 0/46 (0%) | 3/48 (6.3%) | ||
| Hiccups | 2/46 (4.3%) | 3/48 (6.3%) | ||
| Pharyngolaryngeal pain | 11/46 (23.9%) | 5/48 (10.4%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 6/46 (13%) | 10/48 (20.8%) | ||
| Erythema | 2/46 (4.3%) | 8/48 (16.7%) | ||
| Hyperhidrosis | 3/46 (6.5%) | 2/48 (4.2%) | ||
| Pruritus | 1/46 (2.2%) | 4/48 (8.3%) | ||
| Rash | 5/46 (10.9%) | 4/48 (8.3%) | ||
| Vascular disorders | ||||
| Flushing | 0/46 (0%) | 5/48 (10.4%) | ||
| Thrombophlebitis | 0/46 (0%) | 4/48 (8.3%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Hans Olivecrona, MD PhD |
|---|---|
| Organization | Biovitrum |
| Phone | +46 8 697 20 00 |
| hans.olivecrona@sobi.com |
- 20030185