- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00626639
A Study of Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer Receiving Postoperative Radiotherapy and Concurrent Chemotherapy
A Phase 1/2 Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Weekly Doses of Palifermin (rHuKGF) for the Reduction of Oral Mucositis in Subjects With Locally Advanced Head and Neck Cancer (HNC) Receiving Postoperative Radiotherapy With Concurrent Chemotherapy
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
- Fase 1
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- History of newly diagnosed histologically confirmed squamous cell carcinoma (American Joint Committee on Cancer [AJCC] Stage II, III, IVA, or IVB) involving either the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx, post surgical resection (R0, R1)
- Scheduled to receive adjuvant concurrent chemoradiation treatment within 12 weeks of surgery
- High-risk subject defined by presence of at least one of the following: R1 resection margins; T3 or T4 tumor stage; 3 or more positive lymph node metastases; <3 lymph node metastases with extracapsular extension of the disease
- Radiation treatment field to receive planned dose of at least 50Gy to areas of the oral cavity/oropharynx mucosa that can be visualized
Exclusion Criteria:
- Tumors of the lips, paranasal sinuses, salivary glands, or of unknown primary tumors
- Metastatic disease (M1) / Stage IV C
- Presence or history of any other primary malignancy
- History of pancreatitis
- 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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Støttende pleje
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Dobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Placebo komparator: 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.
|
Administered by intravenous (IV) bolus injection
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])
100 mg/m^2 intravenously (IV) on days 1, 22 and 43.
|
Eksperimentel: 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.
|
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])
100 mg/m^2 intravenously (IV) on days 1, 22 and 43.
Administered by intravenous (IV) bolus injection
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Number of Participants With Adverse Events (AEs)
Tidsramme: Up to Week 12 (or Week 15 for participants with severe OM was not resolved by Week 12)
|
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
Tidsramme: Day -3 predose and 24 or 48 hours post-dose
|
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
Tidsramme: 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
|
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
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Number of Participants With Severe Oral Mucositis (OM) (Adapted RTOG/EORTC Grade ≥3)
Tidsramme: Assessed daily up to Week 12 (or Week 15 if severe oral mucositis not resolved ≤ adapted RTOG/EORTC Grade 2 by Week 12).
|
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. |
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
Tidsramme: Assessed daily up to Week 12 (or Week 15 if severe oral mucositis not resolved ≤ adapted RTOG/EORTC Grade 2 by Week 12).
|
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
Tidsramme: Up to Week 12
|
Disease progression was determined by clinical examination and histopathologic examination by the Investigator.
|
Up to Week 12
|
Overall Survival
Tidsramme: During long-term follow-up phase, until December 2015
|
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
|
Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 20040124
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
produkt fremstillet i og eksporteret fra U.S.A.
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
Kliniske forsøg med Placebo
-
SamA Pharmaceutical Co., LtdUkendtAkut bronkitis | Akut øvre luftvejsinfektionKorea, Republikken
-
National Institute on Drug Abuse (NIDA)AfsluttetBrug af cannabisForenede Stater
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyAfsluttetMandlige forsøgspersoner med type II-diabetes (T2DM)Tyskland
-
Heptares Therapeutics LimitedAfsluttetFarmakokinetik | SikkerhedsproblemerDet Forenede Kongerige
-
Regado Biosciences, Inc.AfsluttetSund frivilligForenede Stater
-
Texas A&M UniversityNutraboltAfsluttetGlucose and Insulin Response
-
Longeveron Inc.AfsluttetHypoplastisk venstre hjerte syndromForenede Stater
-
ItalfarmacoAfsluttetBeckers muskeldystrofiHolland, Italien
-
Universidade Estadual de LondrinaConselho Nacional de Desenvolvimento Científico e Tecnológico; Coordination...AfsluttetSund og rask | Kropssammensætning