A study to evaluate the effects of palifermin in reducing mouth ulceration in subjects with locally advanced head and neck cancer

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Weekly Doses of Palifermin (Recombinant Human Keratinocyte Growth Factor, rHuKGF) for the Reduction of Oral Mucositis in Subjects With Advanced Head and Neck Cancer Receiving Radiotherapy With Concurrent Chemotherapy (RT/CT)

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2005-000213-35-CZ

Enrollment

188

Registered

2005-07-14

Start date

2005-08-05

Completion date

Unknown

Last updated

2016-10-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Oral mucositis MedDRA version: 18.1 Level: LLT Classification code 10028130 Term: Mucositis oral System Organ Class: 100000004856

Interventions

Product Name: Palifermin (kepivance) Product Code: V03A F08 Pharmaceutical Form: Powder for solution for injection INN or Proposed INN: Palifermin CAS Number: 162394-19-6 Concentration unit: mg millig

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • Histologically documented squamous cell carcinoma involving either the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx • Absence of second primary tumor confirmed by triple endoscopy or by pharyngo/laryngoscopy combined with imaging evidence (PET or CT scan or MRI) • Newly diagnosed, locally advanced stage HNC (unresectable / unresected disease; American Joint Committee on Cancer [AJCC] Stage III, IVA, or IVB) amenable to RT/CT as the definitive treatment modality • Radiation treatment field to receive planned dose of at least 50Gy to areas of the oral cavity / oropharynx mucosa that can be visualized (Subjects with larynx or hypopharynx tumors are eligible only if the radiation oncologist anticipates at least 2 of the 9 anatomical areas in the oral cavity listed in Section 7.4 of this protocol [Mucositis Assessments] will receive a total dose of 50 Gy). • Signed informed consent • Subject is 18 years of age or older • ECOG performance status (PS) = 2 • Planned interval 3.5 x 10e9/L or - Absolute neutrophil count (ANC) > 1.5 x 10e9/L - Platelet count = 100 x 10e9/L - Serum bilirubin = 1.5 x institutional upper limits of normal (ULN) - Serum creatinine = 2.0 mg/dL; Subjects with a serum creatinine = 1.4 mg/dL and = 2.0 mg/dL need to demonstrate a 24-hr urinary creatinine clearance = 50 mL/min - Serum or urine pregnancy test: Negative Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 162 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 26

Exclusion criteria

Exclusion criteria: • Tumors of the lips, paranasal sinuses, salivary glands, or of unknown primary • Metastatic disease (M1) / Stage IV C • 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 > 3 years) • History of pancreatitis • Plan to remove the tumor surgically before completing the protocol RT / CT course • Prior radiotherapy to the site of disease • Prior chemotherapy • Other investigational procedures • Thirty days or less since receiving an investigational product or device in another clinical trial. Current enrollment in another clinical trial is not permitted unless the sole purpose of the trial is for long-term follow-up/ survival data. • Pregnant or breast-feeding women • Refusal to use adequate contraceptive devices during treatment phase • Known sensitivity to any of the products administered during dosing, including E coli-derived products • Known to be sero-positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) • Previous treatment on this study or with other keratinocyte growth factors • Compromised ability of the subject to give written informed consent and/or to comply with study procedures • Refusal to give written informed consent to participate in this study and to sign the hospital information release form • Unwilling or unable to complete the patient-reported outcome questionnaires • Psychological, social, familial, or geographical reasons that would prevent regular follow-up.

Design outcomes

Primary

Measure	Time frame
Main Objective: To evaluate the efficacy of palifermin administered at the dose of 180 µg/kg IV in 8 weekly doses relative to placebo in reducing the incidence of severe [World Health Organization Grade 3 or 4] oral mucositis (OM) in subjects with locally advanced HNC receiving RT/CT as definitive treatment for their disease.;Secondary Objective: -To assess the safety and tolerability of palifermin at the dose of 180 µg/kg IV in 8 weekly doses compared to placebo during a 7-week course of RT/CT with cisplatin (CDDP) -To evaluate the effect of palifermin on the clinical sequelae of severe OM (eg, average patient-reported mouth and throat soreness score), and on xerostomia -To evaluate long-term effects of palifermin on disease outcome and survival after RT/CT;Primary end point(s): • Incidence (%) of severe oral mucositis (Grades 3 or 4 on the WHO oral mucositis scale);Timepoint(s) of evaluation of this end point: Evaluations of oral mucosal surfaces (mucositis assessments) occur 2 times weekly throughout RT/CT, and 2 times weekly thereafter until severe mucositis (WHO Mucositis Grade 3 or 4) has returned to Grade 2, but not beyond week 15. Within each week, the OM assessments should be performed 3 days apart (+/-1 day).	—

Measure

Time frame

Main Objective: To evaluate the efficacy of palifermin administered at the dose of 180 µg/kg IV in 8 weekly doses relative to placebo in reducing the incidence of severe [World Health Organization Grade 3 or 4] oral mucositis (OM) in subjects with locally advanced HNC receiving RT/CT as definitive treatment for their disease.;Secondary Objective: -To assess the safety and tolerability of palifermin at the dose of 180 µg/kg IV in 8 weekly doses compared to placebo during a 7-week course of RT/CT with cisplatin (CDDP) -To evaluate the effect of palifermin on the clinical sequelae of severe OM (eg, average patient-reported mouth and throat soreness score), and on xerostomia -To evaluate long-term effects of palifermin on disease outcome and survival after RT/CT;Primary end point(s): • Incidence (%) of severe oral mucositis (Grades 3 or 4 on the WHO oral mucositis scale);Timepoint(s) of evaluation of this end point: Evaluations of oral mucosal surfaces (mucositis assessments) occur 2 times weekly throughout RT/CT, and 2 times weekly thereafter until severe mucositis (WHO Mucositis Grade 3 or 4) has returned to Grade 2, but not beyond week 15. Within each week, the OM assessments should be performed 3 days apart (+/-1 day).

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Secondary

Measure	Time frame
Secondary end point(s): • Duration of severe oral mucositis (WHO Grades 3 or 4) • Average patient-reported mouth and throat soreness score (as reported on the Oral Mucositis Weekly Questionnaire for Head and Neck Cancer [OMWQ-HN]) • Time to severe oral mucositis (WHO Grades 3 or 4) • Total dose of opioid analgesics used (mg of morphine equivalents) • Incidence of unplanned breaks in RT =5 days (to include discontinuations of RT) • Incidence of unplanned breaks in CT =5 days (to include discontinuations of CT) • Incidence of xerostomia (CTCAE v3.0 Dry Mouth/Xerostomia scale Grade 2 or higher) Safety Endpoints: Short-term • Incidence of adverse events and laboratory abnormalities using the CTCAE v.3.0 toxicity scales • Incidence of serum anti-palifermin antibody formation • Overall tumor response and loco-regional failure at week 12 Safety Endpoints: Long-term • Time to loco-regional tumor failure • Incidence of second primary tumors • Incidence of other malignancies • Progression-free survival (PFS) • Overall survival (OS) • Incidence of leukoplakia;Timepoint(s) of evaluation of this end point: Evaluations of oral mucosal surfaces occur 2 times weekly throughout RT/CT, and 2 times weekly thereafter until severe mucositis (WHO Mucositis Grade 3 or 4) has returned to Grade 2, but not beyond week 15. Within each week, the OM assessments should be performed 3 days apart (+/-1 day). On the days of the mucositis assessments, all study subjects will be asked to complete the PRO questionnaires BEFORE the clinical evaluation or any clinical procedure. On the days of the oral mucosa assessments, salivary gland changes will be evaluated. During the first 2 weeks of RT, blood samples for serum amylase and lipase testing will be taken on Monday and Friday (Friday before IP administration). During weeks 4, 8, and 12, serum samples will be obtained for anti-palifermin antibody testing.	—

Measure

Time frame

Secondary end point(s): • Duration of severe oral mucositis (WHO Grades 3 or 4) • Average patient-reported mouth and throat soreness score (as reported on the Oral Mucositis Weekly Questionnaire for Head and Neck Cancer [OMWQ-HN]) • Time to severe oral mucositis (WHO Grades 3 or 4) • Total dose of opioid analgesics used (mg of morphine equivalents) • Incidence of unplanned breaks in RT =5 days (to include discontinuations of RT) • Incidence of unplanned breaks in CT =5 days (to include discontinuations of CT) • Incidence of xerostomia (CTCAE v3.0 Dry Mouth/Xerostomia scale Grade 2 or higher) Safety Endpoints: Short-term • Incidence of adverse events and laboratory abnormalities using the CTCAE v.3.0 toxicity scales • Incidence of serum anti-palifermin antibody formation • Overall tumor response and loco-regional failure at week 12 Safety Endpoints: Long-term • Time to loco-regional tumor failure • Incidence of second primary tumors • Incidence of other malignancies • Progression-free survival (PFS) • Overall survival (OS) • Incidence of leukoplakia;Timepoint(s) of evaluation of this end point: Evaluations of oral mucosal surfaces occur 2 times weekly throughout RT/CT, and 2 times weekly thereafter until severe mucositis (WHO Mucositis Grade 3 or 4) has returned to Grade 2, but not beyond week 15. Within each week, the OM assessments should be performed 3 days apart (+/-1 day). On the days of the mucositis assessments, all study subjects will be asked to complete the PRO questionnaires BEFORE the clinical evaluation or any clinical procedure. On the days of the oral mucosa assessments, salivary gland changes will be evaluated. During the first 2 weeks of RT, blood samples for serum amylase and lipase testing will be taken on Monday and Friday (Friday before IP administration). During weeks 4, 8, and 12, serum samples will be obtained for anti-palifermin antibody testing.

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Countries

Austria, Czech Republic, Germany, Hungary, Italy, Poland, United States

Contacts

Public ContactIHQ Medical Info - Clinical Trials

Amgen (EUROPE) GmbH

MedinfoInternational@amgen.com

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026