MucositisPhase 3NCT00101582
Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer
A Phase 3 study testing palifermin, cisplatin chemotherapy and Radiotherapy in people with Mucositis and Solid Tumors, run by Swedish Orphan Biovitrum.
Trial summary
The purpose of this research study is to test the safety and effectiveness of palifermin to determine if weekly doses can be safely administered to reduce the incidence (occurrence of), duration (length of time) and severity (amount of pain) of oral mucositis (painful sores in the mouth). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mucositis, Solid Tumors, Stomatitis
- What is being tested?
- palifermin, cisplatin chemotherapy and Radiotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 188 participants
- Where
- No sites listed yet
- Study dates
- Aug 2005to Aug 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically documented squamous cell carcinoma involving either the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx
- Newly diagnosed, locally advanced stage head and neck cancer (unresectable/unresected disease); American Joint Committee on Cancer [AJCC] Stage III, IVA or IVB amenable to radiotherapy with concurrent chemotherapy as the definitive treatment modality
- At least 50 Gray of radiation treatment to areas of the oral cavity/oropharynx mucosa that can be visualized
- Concurrent chemotherapy regimen of Cisplatin 100mg/m^2 on days 1, 22, and 43
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) less than or equal to 2
- Adequate hematologic, renal and hepatic function
- Negative pregnancy test by serum or urine
- Signed informed consent
Who cannot join
- Presence or history of any other primary malignancy (other than curatively treated in situ cervical cancer, or basal cell carcinoma of the skin without evidence of disease for greater than 3 years)
About this study
Official title: Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Weekly Doses of Palifermin (rHuKGF) for the Reduction of Oral Mucositis in Subjects With Advanced Head and Neck Cancer Receiving Radiotherapy With Concurrent Chemotherapy (RT/CT)
The purpose of this research study is to test the safety and effectiveness of palifermin to determine if weekly doses can be safely administered to reduce the incidence (occurrence of), duration (length of time) and severity (amount of pain) of oral mucositis (painful sores in the mouth). Mucositis is a common side effect for patients receiving chemotherapy (cancer-killing drug) and radiotherapy (cancer-killing x-rays) for the treatment of head and neck cancer (HNC).
Read the detailed description
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 dose of palifermin or placebo at 180 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.
- Being tested
- Placebo, palifermin, cisplatin chemotherapy, Radiotherapy
- Keywords
- SCCHN, Palifermin, Mucositis, Oral Cavity, Oropharynx, Nasopharynx, Hypopharynx, Larynx, Mouth Pain, Mouth Sores, Radiation Therapy, Radiotherapy, Radiochemotherapy, Concurrent Chemotherapy, Xerostomia, Stomatitis, Mucosa, KGF, rHuKGF, Keratinocyte Growth Factor
- Medical subject headings
- Mucositis, Stomatitis, Head and Neck Neoplasms, Carcinoma, Squamous Cell, Laryngeal Diseases, Oral Ulcer, Xerostomia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
paliferminDrug
Also called Kepivance, Recombinant Human Keratinocyte Growth Factor (rHuKGF)
cisplatin chemotherapyDrug
Commercially available cisplatin was administered as an intravenous infusion at a dose of 100 mg/m^2 on Days 1, 22, and 43.
RadiotherapyRadiation
Radiotherapy was delivered in 200 cGy daily fractions, 5 days a week.
| Study group | Role | What they receive |
|---|---|---|
| Palifermin | Experimental | Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course. Receives: Drug: palifermin; Drug: cisplatin chemotherapy; Radiation: Radiotherapy |
| Placebo | Placebo comparator | Participants received a single IV dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course. Receives: Drug: Placebo; Drug: cisplatin chemotherapy; Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Severe (Grade 3 or 4) Oral Mucositis
Participants underwent evaluations of oral mucosal (OM) surfaces (mucositis assessments) 2 times weekly throughout radio/chemotherapy, and 2 times weekly thereafter until severe OM returned to grade ≤ 2 or until Week 15. During each evaluation, the following anatomical areas were assessed: upper lip; lower lip; right cheek; left cheek; right ventral \& lateral tongue; left ventral \& lateral tongue; floor of the mouth; hard palate; soft palate. A trained evaluator documented the findings using the World Health Organization (WHO) oral toxicity scale according to the following: 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.
Measured: Up to Week 15
Secondary outcomes (7)
Duration of Severe (WHO Grade 3 or 4) Oral Mucositis
The duration of severe oral mucositis (OM) was calculated as the number of days from the onset of severe OM (first time a WHO grade 3 or 4 was observed) to the day when severe OM was resolved (first time WHO grade 2 or less was observed after last WHO grade 3 or 4). Durations of 0 days were assigned to those participants who did not experience any WHO grade 3 or 4 during the study.
Measured: Up to 15 weeks
Time to Onset of Severe (WHO Grade 3 or 4) Oral Mucositis
Time to onset of severe (WHO Grade 3 or 4) oral mucositis (OM) was analyzed using the Kaplan-Meier procedure.
Participants without an assessed event by the end of the acute OM evaluation phase were censored at the date of last assessment for severe OM.
Measured: Up to 15 weeks
Number of Participants With Xerostomia at Month 4 (Grade 2 or Higher)
The number of participants with grade 2 or higher xerostomia (dryness of the oral mucosa) at the Month 4 visit, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Dry Mouth/Xerostomia scale.
Measured: Month 4
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 Weekly Questionnaire for Head and Neck Cancer [OMWQ-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).
For each participant, an average patient-reported mouth and throat soreness score was calculated by dividing the sum of the MTS scores at each assessment by the total number of assessments.
Measured: Assessed twice a week for up to 15 weeks.
Total Dose of Opioid Analgesics Used for Mucositis Within 15 Weeks
The total dose of opioid analgesics (mg of intravenous [IV] morphine equivalents) used by all participants.
Participants with at least one reported administration of opioid analgesic (parenteral, peroral or transdermal) were considered to have received opioid analgesics. The total dose of opioid analgesics is the sum of all opioid analgesic administrations that have been converted to morphine equivalents.
Measured: Up to 15 weeks
Number of Participants With Unplanned Breaks in Cisplatin Chemotherapy Treatment
Cisplatin was administered on Days 1, 22, and 43. An unplanned break in cisplatin refers to a delay of ≥ 5 days from the scheduled Day 22 or Day 43 cisplatin administration or a discontinuation of cisplatin for any reason.
Measured: During the 7 weeks of chemotherapy treatment
Number of Participants With Unplanned Breaks in Radiotherapy
Participants with a duration of 5 days or more without an administration of radiotherapy or who discontinue radiotherapy prior to completion of planned radiotherapy were considered to have an unplanned break in radiotherapy.
Measured: During the 7 weeks of radiotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2005 (estimated)
- Study startAug 2005
- Primary completionSep 2007
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MucositisStudies of the same condition, open and under way.
- More trials run by Swedish Orphan BiovitrumThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 188 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swedish Orphan Biovitrum
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Amgen
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00101582
- Sponsor's protocol ID
- 20020402
- Status last verified
- Aug 2016
- First submitted
- 12 Jan 2005
- Last updated
- 27 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Weekly Doses of Palifermin (rHuKGF) for the Reduction of Oral Mucositis in Subjects With Advanced Head and Neck Cancer Receiving Radiotherapy With Concurrent Chemotherapy (RT/CT)
- ClinicalTrials.gov ID
- NCT00101582
- Acronym / sponsor ID
- 20020402
- Keywords
- SCCHN, Palifermin, Mucositis, Oral Cavity, Oropharynx, Nasopharynx, Hypopharynx, Larynx
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 188 participants (actual)
- Lead sponsor
- Swedish Orphan BiovitrumIndustry (pharma, biotech, devices)
- Collaborators
- Amgen
- Study start
- Aug 2005
- Primary completion
- Sep 2007 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 13 Jan 2005 (estimated)
- Results
- Posted 15 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to test the safety and effectiveness of palifermin to determine if weekly doses can be safely administered to reduce the incidence (occurrence of), duration (length of time) and severity (amount of pain) of oral mucositis (painful sores in the mouth). Mucositis is a common side effect for patients receiving chemotherapy (cancer-killing drug) and radiotherapy (cancer-killing x-rays) for the treatment of head and neck cancer (HNC).
Detailed description
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 dose of palifermin or placebo at 180 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Palifermin | Experimental | Drug: palifermin, Drug: cisplatin chemotherapy, Radiation: RadiotherapyParticipants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course. |
| Placebo | Placebo comparator | Drug: Placebo, Drug: cisplatin chemotherapy, Radiation: RadiotherapyParticipants received a single IV dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically documented squamous cell carcinoma involving either the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx
- Newly diagnosed, locally advanced stage head and neck cancer (unresectable/unresected disease); American Joint Committee on Cancer [AJCC] Stage III, IVA or IVB amenable to radiotherapy with concurrent chemotherapy as the definitive treatment modality
- At least 50 Gray of radiation treatment to areas of the oral cavity/oropharynx mucosa that can be visualized
- Concurrent chemotherapy regimen of Cisplatin 100mg/m^2 on days 1, 22, and 43
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) less than or equal to 2
Key exclusion criteria (1 listed)
- Presence or history of any other primary malignancy (other than curatively treated in situ cervical cancer, or basal cell carcinoma of the skin without evidence of disease for greater than 3 years)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo | Drug | Placebo |
| paliferminAlso: Kepivance, Recombinant Human Keratinocyte Growth Factor (rHuKGF) | Drug | Palifermin |
| cisplatin chemotherapyCommercially available cisplatin was administered as an intravenous infusion at a dose of 100 mg/m^2 on Days 1, 22, and 43. | Drug | Palifermin, Placebo |
| RadiotherapyRadiotherapy was delivered in 200 cGy daily fractions, 5 days a week. | Radiation | Palifermin, Placebo |
Primary outcome
Number of Participants With Severe (Grade 3 or 4) Oral Mucositis
Time frame: Up to Week 15
Participants underwent evaluations of oral mucosal (OM) surfaces (mucositis assessments) 2 times weekly throughout radio/chemotherapy, and 2 times weekly thereafter until severe OM returned to grade ≤ 2 or until Week 15. During each evaluation, the following anatomical areas were assessed: upper lip; lower lip; right cheek; left cheek; right ventral \& lateral tongue; left ventral \& lateral tongue; floor of the mouth; hard palate; soft palate. A trained evaluator documented the findings using the World Health Organization (WHO) oral toxicity scale according to the following: 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.
7 secondary outcomes
Duration of Severe (WHO Grade 3 or 4) Oral Mucositis
Time frame: Up to 15 weeks
Time to Onset of Severe (WHO Grade 3 or 4) Oral Mucositis
Time frame: Up to 15 weeks
Number of Participants With Xerostomia at Month 4 (Grade 2 or Higher)
Time frame: Month 4
Patient-Reported Mouth and Throat Soreness Score
Time frame: Assessed twice a week for up to 15 weeks.
Total Dose of Opioid Analgesics Used for Mucositis Within 15 Weeks
Time frame: Up to 15 weeks
Number of Participants With Unplanned Breaks in Cisplatin Chemotherapy Treatment
Time frame: During the 7 weeks of chemotherapy treatment
Number of Participants With Unplanned Breaks in Radiotherapy
Time frame: During the 7 weeks of radiotherapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing palifermin, cisplatin chemotherapy and Radiotherapy in people with Mucositis and Solid Tumors, run by Swedish Orphan Biovitrum.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Severe (Grade 3 or 4) Oral Mucositis (time frame: Up to Week 15). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2016.