This trial will study the safety and tolerability and disease survival rates in adult patients with recurrent/metastatic (R/M) HNSCC when treated with carboplatin or cisplatin, paclitaxel, and toripalimab.
Pathologically confirmed and previously untreated squamous cell carcinoma of the larynx or hypopharynx
AJCC 8th Edition Stage III - IV disease (T1-T2/N1-N3, T3-T4/N0-N3)
Disease (primary & nodal) must be potentially surgically resectable and curable with conventional surgery and CRT
ECOG PS 0 - 2
Prior treatment for head and neck cancer
Unresectable laryngeal or hypopharyngeal squamous cell carcinoma
Distant metastatic disease
Has an active autoimmune disease requiring systemic treatment within the past 3 months, or a syndrome that requires ongoing systemic steroids or immunosuppressive agents. Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic therapy or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism or Sjogren's syndrome will not be excluded from the study.
Sequential
Toripalimab
DrugA monoclonal antibody (recombinant humanized programmed cell death protein 1 (PD-1) monoclonal antibody that acts as a checkpoint inhibitor) used for the treatment of melanoma and nasopharyngeal carcinoma.
Carboplatin
DrugA chemotherapy medication classified as an alkylating agent. It contains the metal platinum, which binds to DNA in cancer cells, preventing their replication and leading to cell death. This mechanism makes it effective against rapidly dividing cells, such as cancer cells.
Cisplatin
Drug\*Can be used in place of carboplatin at the investigator's discretion. A chemotherapy medication classified as an alkylating agent. It contains the metal platinum, which binds to DNA in cancer cells, preventing their replication and leading to cell death. This mechanism makes it effective against rapidly dividing cells, such as cancer cells.
Paclitaxel
DrugA chemotherapy drug that works by slowing or stopping cancer cell growth.
Radiation Therapy
RadiationMegavoltage energy photon beam irradiation. Any treatment planning and delivery system that has been credentialed for head and neck intensity-modulated radiotherapy (IMRT). Simultaneous integrated boost and sequential boost techniques (discretion of treating physician). Total doses delivered to each Planning Target Volume (PTV) (in 33-35 fractions): High: 70 Gy, Boost (if applicable): 66 Gy, Intermediate: 60-63 Gy, Elective: 56-57 Gy A sequential boost will consist of treatment of the combined PTVs 25 fractions followed by three sequential cone-downs targeting (Intermediate + Boost + High); (Boost + High); and High. Total doses for the PTVs: High: 70 Gy, Boost (if applicable): 66 Gy, Intermediate: 60 Gy, Elective: 50 Gy.
1-Year Disease-free survival (DFS)
Proportion of patients who have not experienced disease recurrence/progression or death from any cause at 1 year from start of treatment. Radiologic (CT or MRI) imaging as well as direct visualization by laryngoscopy will be used to assess disease with recurrence requiring a biopsy to be considered positive.
Overall Survival (OS)
Median time from initiation of study therapy to death from any cause.
Larynx preservation rate
The proportion of responding patients (without disease recurrence/progression or death from any cause) who do not undergo laryngectomy during the study period. Radiologic (CT or MRI) imaging as well as direct visualization by laryngoscopy will be used to assess disease with recurrence requiring a biopsy to be considered positive.
Endoscopic evaluation of swallowing (FEES)
A portable procedure in which a thin, flexible endoscope is passed through the nose to view the pharynx and larynx during swallowing, allowing the physician to directly observe and assess the patient's swallowing mechanics. The physician will indicate the presence or absence of impairment of the pharynx and/or larynx that effects swallowing.
Neck Dissection Impairment Index (NDII)
Patient Reported Outcome Measure (PROM) is a 10-item, self-report instrument. A 5-level Likert scale is used for responses ranging from 'not at all' = 10 to 'a lot' = 0 related to pain/discomfort and limitation of movement as a result of cancer treatment. The NDII scores range from 0 to 100, with higher scores indicating better shoulder functioning and quality of life (QOL). Factors such as age, weight, radiation treatment, and neck dissection type significantly affect the QOL score.
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Matthew Spector
Lead sponsor
University of Pittsburgh
Sponsor institution
Coherus Oncology, Inc.
Collaborator
