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
29 maggio 2017 aggiornato da: Swedish Orphan Biovitrum
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
Oral Mucositis associated with adjuvant radiation and concurrent chemotherapy in postoperative Head and Neck setting
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Interventistico
Iscrizione (Effettivo)
5
Fase
- Fase 2
- Fase 1
Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
18 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
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
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Terapia di supporto
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Doppio
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Comparatore placebo: 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.
|
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Sperimentale: 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
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Number of Participants With Adverse Events (AEs)
Lasso di tempo: 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.
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Up to Week 12 (or Week 15 for participants with severe OM was not resolved by Week 12)
|
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Ratio of Ki67-positive Cells Before and After Palifermin Treatment
Lasso di tempo: 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
|
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Pharmacokinetics of Palifermin
Lasso di tempo: 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
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Number of Participants With Severe Oral Mucositis (OM) (Adapted RTOG/EORTC Grade ≥3)
Lasso di tempo: 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).
|
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Patient-Reported Mouth and Throat Soreness Score
Lasso di tempo: 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).
|
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Number of Participants With Disease Progression by Week 12
Lasso di tempo: Up to Week 12
|
Disease progression was determined by clinical examination and histopathologic examination by the Investigator.
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Up to Week 12
|
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Overall Survival
Lasso di tempo: 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.
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During long-term follow-up phase, until December 2015
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Collaboratori
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 luglio 2005
Completamento primario (Effettivo)
1 maggio 2007
Completamento dello studio (Effettivo)
1 luglio 2015
Date di iscrizione allo studio
Primo inviato
21 febbraio 2008
Primo inviato che soddisfa i criteri di controllo qualità
21 febbraio 2008
Primo Inserito (Stima)
29 febbraio 2008
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
21 giugno 2017
Ultimo aggiornamento inviato che soddisfa i criteri QC
29 maggio 2017
Ultimo verificato
1 maggio 2017
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- 20040124
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
No
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
No
prodotto fabbricato ed esportato dagli Stati Uniti
No
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