This phase II trial studies how well cisplatin, docetaxel, and pembrolizumab work in treating patients with stage II-III laryngeal cancer. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cisplatin, docetaxel, and pembrolizumab may help to control the disease.
PRIMARY OBJECTIVES: I. To determine the clinical benefit rate (CBR) of patients with stage II or III larynx squamous cell carcinoma (SCC) after 2 cycles of pembrolizumab, cisplatin and docetaxel (PCD), and the pathologic complete response (pCR) rate after 4 cycles of PCD. SECONDARY OBJECTIVES: I. To determine safety and tolerability of PCD in patients with larynx SCC. II. To determine the laryngeal preservation rate (LPR) at 2 years in the overall population and in the subgroup who achieves a pCR. III. To determine the 2 year relapse-free survival (RFS) and overall survival (OS) in the overall population and in the subgroup who achieves a pCR. IV. To determine patient-reported outcomes (PROs) using M. D. Anderson Symptom Inventory-Head and Neck (MDASI-HN) and swallow function using Dynamic Imaging Grade of Swallowing Toxicity (DIGEST). EXPLORATORY OBJECTIVES: I. To assess predictive tissue and blood-based biomarkers of benefit from PCD in larynx SCC. OUTLINE: Patients receive cisplatin intravenously (IV) over 1 hour, docetaxel IV over 1 hour (patients who develop significant adverse events to cisplatin treatment may receive carboplatin IV over 1 hour instead), and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who completely respond to the study drugs (the disease appears to go away) then receive pembrolizumab IV over 30 minutes on day 1 for 4 additional cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 3 weeks, then every 6-12 weeks for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
28
M D Anderson Cancer Center
Houston, Texas, United States
CBR (After 2 Cycles of PCD) AND pCR (After 4 Cycles of PCD)
To determine the clinical benefit rate (CBR) of patients with stage II or III larynx squamous cell carcinoma (SCC) after 2 cycles of pembrolizumab, cisplatin and docetaxel (PCD), and the pathologic complete response (pCR) rate after 4 cycles of PCD. The CBR rate of patients with stage II or III larynx SCC after 2 cycles of PCD is 100%, excluding one patient (measurable data not available). The pCR rate after 4 cycles of PCD is 75.0%. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v.1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), diseappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient growth to qualify for PD; Progressive Disease (PD), \>= 20% increase in the sum of the longest diameter with an absolute increase of at least 5 mm or the appearance of new lesions
Time frame: CBR after 2 cycles (6 weeks), pCR after 4 cycles (12 weeks), end of study (up to 3 years)
Safety and Tolerability of PCD in Patients With Larynx SCC -- Number of Adverse Events
Adverse events (AEs) are categorized as follows: Treatment-Emergent Adverse Events (TEAEs), which refer to any AEs that arise or worsen in severity after the initiation of treatment with the study product; and Treatment-Related Adverse Events (TRAEs), defined as TEAEs that are considered possibly, probably, or definitely related to the treatment. Adverse Events were graded 1 to 5 via CTAE 4.0 guidelines. All AEs, whether serious or non-serious, will be captured from the time of the first administration of the investigational agent until 30 days following the last dose of study drug or until the initiation of alternative anticancer therapy
Time frame: first administration of investigational agent until 30 days following last dose of study drug; approximately 3 years and 11 months
Larynx Preservation Rates for Overall and pCR Patients at 2 Years
To determine the laryngeal preservation rate (LPR) at 2 years in the overall population and in the subgroup who achieves a pCR. KM method was used. The larynx preservation rate is calculated by dividing the number of patients who did not need a laryngectomy (either total or partial) after initial treatment by the total number of patients who were candidates for such a treatment.
Time frame: study registration to laryngectomy or date of censoring (2 years follow up)
To Determine the 2-year Relapse-free Survival (RFS) and Overall Survival (OS) in the Overall Population and in the Subgroup Who Achieves a pCR (RFS)
Relapse free survival is defined as the time from study registration to recurrence after local therapy or death from any cause. Recurrence was counted only if it occurred after definitive local therapy (surgery and/or radiotherapy). Patients achieving durable complete responses to PCD without local therapy, and patients receiving local therapy without subsequent recurrence, were censored at last follow-up.
Time frame: from first study registration to recurrence after local therapy or death from any cause (up to 2 years follow up)
To Determine the 2-year Relapse-free Survival (RFS) and Overall Survival (OS) in the Overall Population and in the Subgroup Who Achieves a pCR. (OS)
Overall survival is defined from study registration to death due to any cause or to the date of censoring measure at the last contact. KM method was used.
Time frame: first study registration to death due to any cause or date of censuring (up to 2 years follow up)
DIGEST
To determine swallow function using Dynamic Imaging Grade of Swallowing Toxicity (DIGEST). DIGEST is a validated psychometric tool used during modified barium swallow studies (MBSSs) to grade swallowing safety, efficiency, and overall pharyngeal swallow function. Scores ranging from 0 to 4, where 0 indicates no impairment, 1=mild, 2=moderate, 3=severe, 4=life threatening. The DIGEST grade was collected at three time points: baseline, 6 months post-treatment and long-term follow-up. One subject without any DIGEST data was excluded from analysis. A linear mixed-effects model was used to evaluate the effects of treatment group (chemo-IO alone vs. radiation/surgery) and time on DIGEST grade across three time points.
Time frame: baseline, 6 months post treatment, long-term follow up (up to two years)
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