ERBITUX® Followed by Adjuvant Treatment With Chemoradiation and ERBITUX® for Locally Advanced Head and Neck Squamous Cell Carcinoma
Phase II Study of Neoadjuvant Immune Biomarker Modulation With Cetuximab Followed by Adjuvant Therapy With Concurrent Chemoradiotherapy or Radiotherapy With or Without Cetuximab for Locally Advanced Head and Neck Squamous Cell Carcinoma
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Detailní popis
Typ studie
Typ studie
Zápis (Aktuální)
Zápis
Fáze
Fáze
- Fáze 2
Kontakty a umístění
Studijní místa
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Pennsylvania
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Pittsburgh, Pennsylvania, Spojené státy, 15232
- UPCI - Hillman Cancer Center
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Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Histologically or cytologically confirmed, previously untreated HNC. Clinical stage III or IVA disease without distant metastases as determined by CT, and as defined by the American Joint Committee on Cancer Staging System, Sixth edition (See Appendix I).
- Primary tumors of the oral cavity, oropharynx, hypopharynx, or larynx will be included. Primary tumors of the sinuses, paranasal sinuses, or nasopharynx, or unknown primary tumors are NOT allowed.
- Macroscopic complete resection of the primary tumor must be planned.
- Age greater than or equal to 18 years.
- ECOG performance status 0-1.
Adequate hematologic, renal and hepatic function, as defined by:
- Absolute neutrophil count (ANC) greater than or equal to 1,500/ul, platelets greater than or equal to 100,000/ul.
- Creatinine clearance > 40
- Bilirubin less than or equal to 1.5 x ULN, AST or ALT less than or equal to 2.5 x ULN.
- Have signed written informed consent.
Exclusion Criteria:
- Subjects who fail to meet the above criteria.
- Prior severe infusion reaction to a monoclonal antibody.
- Pregnancy or breastfeeding. Women of childbearing potential (WOCBP) must practice acceptable methods of birth control to prevent pregnancy. Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.
- All WOCBP MUST have a negative pregnancy test within 7 days prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation. The Investigator must immediately notify BMS in the event of a confirmed pregnancy in a patient participating in the study.
- Subjects with an ECOG performance status of 2 or worse.
- Evidence of distant metastasis.
- Any other malignancy active within 5 years except for non-melanoma skin cancer or carcinoma in situ of the cervix, DCIS or LCIS of the breast.
- Prior history of HNC.
- Prior therapy targeting the EGFR pathway.
- Any unresolved chronic toxicity greater than or equal to grade 2 from previous anticancer therapy (except alopecia), according to Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
- Acute hepatitis, known HIV, or active uncontrolled infection.
- History of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, myocardial infarction within prior 6 months, untreated known coronary artery disease, uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
- Uncontrolled peptic or gastric ulcer disease, or gastrointestinal bleeding within prior 6 months.
- Active alcohol abuse or other illness that carries a likelihood of inability to comply with study treatment and follow-up.
- Treatment with a non-approved or investigational drug within 30 days prior to Day 1 of study treatment.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
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Experimentální: Neo-Adjuvant Cetuximab
Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation + Cisplatin (or Carboplatin) NOTE: Based the results of surgery if the treating physician feels patient is not a candidate for chemotherapy, radiation can be given alone or with cetuximab. |
Pre-Surgery: IV, 400 mg/m2 day 1 then 250 mg/m2 alone days 8 and 15; Post-surgery: IV, 250 mg/m2 weekly concurrent with RT
Ostatní jména:
Surgery for tumor
Radiation (2 Gy/d) to min of 60 Gy + max of 66 Gy post-surgery
Cisplatin 30 mg/m2 or carboplatin AUC 1.5-2/week weekly, Concurrent with radiotherapy
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Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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NK Cell Activation
Časové okno: Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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Cetuximab-mediated NK cell activation (percentage of activity) measures at pre-/post-cetuximab exposure for patients in peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL) and in those patients that did and did not respond to treatment.
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Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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Serum Cytokines Levels
Časové okno: Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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Serum cytokines levels measured at pre-/post-cetuximab, exposure measured in picogram per milliliter of plasma (pg/ml)
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Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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T Cell Activation
Časové okno: Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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T cell activation measured at pre-/post-cetuximab exposure
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Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Frequency of EGFR-specific T Cells (EGFR853-861 Peptide-specific Tetramer+ CD8+T Cells)
Časové okno: Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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Difference in frequency of circulating EGFR-specific T cells between cetuximab-treated and cetuximab-naive patients
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Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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Progression-free Survival (PFS)
Časové okno: Up to 54 months
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The length of time during and after study treatment that participants lived with disease that did not progress per RECIST 1.0.
Progression per RECIST 1.0 is defined as a 20% increase the in longest dimension (LD) lesion from Nadir.
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Up to 54 months
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Overall Survival (OS)
Časové okno: Up to 2 years
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Number of patients remaining alive.
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Up to 2 years
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Objective Response (Rate)
Časové okno: Up to 2 years
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The percentage of participants that experienced a response to study treatment, per RECIST 1.0: Number of participant with (Complete Response (CR) + number of participants with Partial Response (PR) / Total number of participants evaluable for response.
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Up to 2 years
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3-year Progression-free Survival (PFS)
Časové okno: 3 years
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Percentage of participants alive at 3 years that did not experience disease progression per RECIST 1.0.
Progression per RECIST 1.0 is defined as a 20% increase the in longest dimension (LD) lesion from Nadir.
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3 years
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Change in Tumor Size
Časové okno: Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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Largest percent change (decrease) in tumor size before and after neoadjuvant cetuximab.
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Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Spolupracovníci
Spolupracovníci
Vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Rober L Ferris, MD, PhD, University of Pittsburgh Med Ctr (UPCI)
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Začátek studia
Primární dokončení (Aktuální)
Primární dokončení
Dokončení studie (Aktuální)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Novotvary podle histologického typu
- Novotvary
- Novotvary podle místa
- Novotvary, žlázové a epiteliální
- Novotvary hlavy a krku
- Novotvary, dlaždicové buňky
- Karcinom
- Karcinom, skvamózní buňky
- Spinocelulární karcinom hlavy a krku
- Antineoplastická činidla
- Antineoplastická činidla, Imunologická
- Karboplatina
- Cetuximab
Další identifikační čísla studie
Další identifikační čísla studie
- UPCI 08-013
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