Safety Testing of Adding Nivolumab to Chemotherapy in Patients With Intermediate and High-Risk Local-Regionally Advanced Head and Neck Cancer
22. november 2022 oppdatert av: RTOG Foundation, Inc.
Safety Evaluations of Nivolumab (Anti-PD-1) Added To Chemotherapy (CRT) Platforms In Patients With Intermediate And High-Risk Local-Regionally Advanced Head and Neck Squamous Cell Carcinoma
This study will evaluate the safety of adding nivolumab to several chemotherapy platforms with weekly cisplatin, high-dose cisplatin, cetuximab or radiation therapy alone.
Studieoversikt
Status
Fullført
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
40
Fase
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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California
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Palo Alto, California, Forente stater, 94304
- Stanford Cancer Institute
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Florida
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Orlando, Florida, Forente stater, 32806
- University of Florida Cancer Center at Orlando Health
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Georgia
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Atlanta, Georgia, Forente stater, 30322
- Emory University/Winship Cancer Institute
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Kentucky
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Louisville, Kentucky, Forente stater, 40202
- University of Louisville
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Ohio
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Cleveland, Ohio, Forente stater, 44106
- University Hospitals Cleveland Medical Center
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Columbus, Ohio, Forente stater, 43210
- Ohio State University
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Oregon
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Portland, Oregon, Forente stater, 97213
- Providence Portland Medical Center
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Pennsylvania
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Pittsburgh, Pennsylvania, Forente stater, 15232
- UPMC - Shadyside Hospital
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Texas
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Houston, Texas, Forente stater, 77030
- MD Anderson Cancer Center
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Virginia
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Falls Church, Virginia, Forente stater, 22042
- INOVA Fairfax Hospital
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Wisconsin
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Madison, Wisconsin, Forente stater, 53792
- University of Wisconsin Hospital and Clinics
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
- Histologically or cytologically-confirmed diagnosis of HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx.
- Intermediate-risk group: Oropharynx cancer that is p16-positive by immunohistochemistry with smoking status > 10 Pack-years, stage T1-2N2b-N3 OR ≤ 10 pack-years, stage T4N0-N3 or T1-3N3.
High-risk group: Oral cavity, larynx, hypopharynx, or p16-negative oropharynx cancer, stage T1-2N2a-N3 or T3-4-N0-3 based on the following diagnostic workup:
- Mandatory submission of H&E and p16 stained slides for central review of p16 staining is required for oropharyngeal patients and H&E stained slide block (or punch biopsy of paraffin block) for PD-L1 expression analysis for all patients
- History/physical examination within 28 days prior to registration
- Examination by Radiation Oncologist, Medical Oncologist, and Ear, Nose, Throat (ENT) or Head & Neck Surgeon within 28 days prior to registration
- Fiberoptic exam with laryngopharyngoscopy within 28 days prior to registration
- Diagnostic quality, cross sectional imaging of the thorax within 28 days prior to registration; 18-F-FDG-PET/CT or conventional CT are acceptable.
- Diagnostic quality CT or MRI of neck, with contrast, within 28 days prior to registration; a 18-F-FDG-PET/CT of the neck only is acceptable as a substitute if the CT is of diagnostic quality and with IV contrast.
- Age ≥ 18 years
- The trial is open to both genders
Exclusion Criteria:
- Definitive clinical or radiologic evidence of distant (beyond cervical lymph node and neck tissue) metastatic disease.
- Patients with oral cavity cancer are excluded from participation if resection of the primary tumor is considered technically feasible by an oral or head and neck cancers surgical subspecialist.
- Carcinoma of the neck of unknown primary site origin (even if p16-positive).
- Absence of RECIST, v. 1.1 defined measurable disease.
- Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. Patients with RECIST, v. 1.1 evaluable remaining cancer either in the neck or primary site remain eligible.
- Simultaneous primary cancers or separate bilateral primary tumor sites.
- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).
- Prior systemic chemotherapy for the study cancer.
- Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
- Patients with active autoimmune disease, with exceptions of vitiligo, type I diabetes mellitus, hypothyroidism and psoriasis.
- Use of systemic corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration, with exception of inhaled or topical steroids.
- Known immunosuppressive disease, for example HIV infection or history of bone marrow transplant or chronic lymphocytic leukemia (CLL).
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Sekvensiell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Arm 1 (Nivolumab + Cisplatin)
Patients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT.
Cisplatin will be given weekly.
IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy.
Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation.
Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
|
Anti-PD-1 targeted immunotherapy
Andre navn:
Anti-cancer alkylating agent
Andre navn:
High-precision radiotherapy
Andre navn:
|
|
Eksperimentell: Arm 2 (Nivolumab + High-dose Cisplatin)
Patients will receive Nivolumab via IV administration starting 14 days prior to IMRT, then Day 1 of IMRT and then every 21 days for 6 doses.
Cisplatin will be given every 21 days for 3 doses.
IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy.
Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation.
Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
|
Anti-PD-1 targeted immunotherapy
Andre navn:
Anti-cancer alkylating agent
Andre navn:
High-precision radiotherapy
Andre navn:
|
|
Eksperimentell: Arm 3 (Nivolumab + Cetuximab)
Patients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT.
Cetuximab will be given for 7 doses.
IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy.
Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation.
Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
|
Anti-PD-1 targeted immunotherapy
Andre navn:
High-precision radiotherapy
Andre navn:
Epidermal Growth Factor Receptor (EGFR) antagonist
Andre navn:
|
|
Eksperimentell: Arm 4 (Nivolumab + IMRT)
Patients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT.
IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy.
Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation.
Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
|
Anti-PD-1 targeted immunotherapy
Andre navn:
High-precision radiotherapy
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Dose Limiting Toxicity (DLT)
Tidsramme: From the first dose of nivolumab to 28 days after the completion of radiation therapy.
|
A nivolumab attributable, dose-limiting toxicity (DLT) will be defined as follows: 1) Any ≥ grade 3 adverse event (CTCAE, v. 4) that is related to nivolumab that does not resolve to grade 1 or less within 28 days; 2) A delay in radiotherapy of > 2 weeks due to toxicity related to nivolumab; 3) Inability to complete radiotherapy due to toxicity related to nivolumab; 4) Inability to receive an adequate dose (≥ 70%) of cisplatin (Arm 1 and 2) or cetuximab (Arm 3) due to toxicity definitely related to nivolumab. |
From the first dose of nivolumab to 28 days after the completion of radiation therapy.
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Maura Gillison, MD, PhD, RTOG Foundation
- Hovedetterforsker: Robert Ferris, MD, PhD, RTOG Foundation
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. juni 2016
Primær fullføring (Faktiske)
25. september 2018
Studiet fullført (Faktiske)
21. februar 2022
Datoer for studieregistrering
Først innsendt
4. mai 2016
Først innsendt som oppfylte QC-kriteriene
4. mai 2016
Først lagt ut (Anslag)
6. mai 2016
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
29. november 2022
Siste oppdatering sendt inn som oppfylte QC-kriteriene
22. november 2022
Sist bekreftet
1. november 2022
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Neoplasmer etter histologisk type
- Neoplasmer
- Neoplasmer etter nettsted
- Neoplasmer, kjertel og epitel
- Neoplasmer i hode og nakke
- Neoplasmer, plateepitelceller
- Karsinom
- Karsinom, plateepitel
- Plateepitelkarsinom i hode og nakke
- Molekylære mekanismer for farmakologisk virkning
- Antineoplastiske midler
- Antineoplastiske midler, immunologiske
- Immune Checkpoint-hemmere
- Nivolumab
- Cetuximab
Andre studie-ID-numre
- RTOG 3504
- RF 3504 (Annen identifikator: RTOG Foundation)
- CA209-410 (Annen identifikator: Bristol-Myers Squibb)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Nei
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .