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.
Currently, for patients with locally advanced laryngeal or hypopharyngeal squamous cell carcinoma (SCC), there is the option of total laryngectomy (TL) followed by adjuvant pathology driven therapy (RT or CRT) or an organ preservation approach. Total laryngectomy is a particularly morbid surgery, leaving a patient breathing through the neck for the rest of their life. In recent years however, upfront total laryngectomy with adjuvant RT has been in focus to growing concern of reduced overall survival rates in advanced laryngeal and hypopharyngeal SCC, particularly in patients with T4 disease. As such, upfront TL with adjuvant RT or CRT is typical, with organ preservation protocols more controversial, for T4 LSCC specifically. This trial provides neoadjuvant (chemo)immunotherapy (induction regimen of platinum (carboplatin or cisplatin), paclitaxel, and toripalimab) allowing for a novel approach to patient bioselection for the treatment of laryngeal cancer. Toripalimab is approved in combination with cisplatin and gemcitabine for the first-line treatment of patients with recurrent and/or metastatic nasopharyngeal carcinoma and has shown to significantly improved PFS and OS when combined with cisplatin and gemcitabine. Patients who show response to neoadjuvant therapy in laryngeal cancer have been shown to have 1) a better survival than patients who do not respond and 2) respond better to nonsurgical therapy. The addition of immunotherapy to chemotherapy has the potential to improve the response rate to neoadjuvant therapy, decrease the number of patients who require total laryngectomy as their primary treatment, and to improve the survival of patients with this highly morbid disease.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
87
A 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.
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.
\*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.
UPMC Hillman Cancer
Pittsburgh, Pennsylvania, United States
RECRUITING1-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.
Time frame: At 1 year
Overall Survival (OS)
Median time from initiation of study therapy to death from any cause.
Time frame: Up to 5 years
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.
Time frame: Up to 5 years
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.
Time frame: At Baseline, at 9 weeks, at 6 months after start of treatment, up to 1 year
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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A chemotherapy drug that works by slowing or stopping cancer cell growth.
Megavoltage 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.
Time frame: At Baseline, at every (21 day) treatment cycle, up to 1-year ± 14 days