Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Laryngeal Diseases

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Oral Squamous Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Carboplatin

Pembrolizumab

Albumin-Bound Paclitaxel

Immunomodulating Agents

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

The intervention will be administered on an outpatient basis. The treatment regimen will consist of combination chemotherapy and immunotherapy administered as: Pembrolizumab PLUS Carboplatin PLUS Paclitaxel.

Pembrolizumab 200 mg intravenously (IV) on day 1 of each 3-week cycle

Carboplatin dosed for area under the curve (AUC) 1.5 IV on days 1, 8, 15 of each 3-week cycle

Paclitaxel 45 mg/m2 on days 1, 8, 15 of 3-week cycle.

Study Nurse

Jeffrey Kettler

Thomas Lycan, Jr., DO

Thomas Lycan, DO

The purpose of this research is to see what effects the treatment regimen chemotherapy (carboplatin and paclitaxel) plus immunotherapy (pembrolizumab), has on patients who have been diagnosed with head/neck squamous cell carcinoma and are unable to take the drug 5-fluorouracil

Primary Objective: To determine if six (6) cycles of pembrolizumab with weekly carboplatin and paclitaxel for the 1st line treatment of metastatic head/neck squamous cell carcinoma patients increases the radiographic response rate as compared to the historical rate for pembrolizumab alone.

Secondary Objective(s):

* To determine if six (6) cycles of pembrolizumab with weekly carboplatin and paclitaxel for the 1st line treatment of metastatic head/neck squamous cell carcinoma patients increases median overall survival (OS) as compared to the historical rate reported for pembrolizumab alone.
* To determine if six (6) cycles of pembrolizumab with weekly carboplatin and paclitaxel followed by pembrolizumab alone for the 1st line treatment of metastatic head/neck squamous cell carcinoma patients increases the median progression-free survival (PFS) as compared to the historical rate reported for pembrolizumab alone.
* To determine the toxicity profile of six (6) cycles of pembrolizumab with weekly carboplatin/paclitaxel/pembrolizumab alone for the 1st line treatment of metastatic head/neck squamous cell carcinoma patients, measured as the proportion of patients with discontinuation of any study drug due to any adverse event of any cause, as compared to the historical proportion reported for platinum/5FU/ pembrolizumab (33%).

First Line Weekly Chemo/Immunotherapy for Metastatic Head/Neck Squamous Cell Carcinoma Patients

Phase II Study of First Line Weekly Chemo/Immunotherapy for Metastatic Head/Neck Squamous Cell Carcinoma Patients

Using RECIST 1.1 will be defined as the percentage of analyzed participants with a complete response - defined as disappearance of all target lesions; or partial response - defined as decrease by ≥ 30% in sum of longest diameter of target lesions when compared to the historical objective response rate (19%) reported for pembrolizumab alone; stable disease (SD): Not meeting criteria for CR, PR, or PD; progressive disease (PD): Increase by ≥ 20% in sum of longest diameter of target lesions or the appearance of one or more new lesions.

Median survival rate will be defined as the time from study registration to death due to any cause and as compared to the historical median reported for pembrolizumab alone. The Kaplan-Meier method will be used to generate survival curves with the intention-to-treat population. Data for patients who are alive or lost to follow-up will be censored for overall survival at the date they were last known to be alive

Median progression-free survival (PFS) defined as the time from study registration to the first documented progressive disease (PD) per RECIST v1.1 criteria (defined as increase by ≥ 20% in sum of longest diameter of target lesions or the appearance of one or more new lesions) based on non-blinded central imaging or else death due to any cause, whichever occurred first; and as compared to the historical value reported for pembrolizumab alone. The Kaplan-Meier method will be used to generate survival curves with the intention-to-treat population.

Participants with discontinuation of any study drug due to adverse events of any cause before 18 weeks as compared to the historical value reported for platinum/5FU/pembrolizumab.

National Cancer Institute (NCI)

Wake Forest University Health Sciences

Antirheumatic Agents

Cyclophosphamide

Durvalumab

Six patients will be enrolled at Dose Level 1 with IRX-2 230 units/day in combination with cyclophosphamide and durvalumab and treated sequentially at least 1 week apart. If less than 2 out of 6 patients have DLTs in Dose Level 1, the dose will be escalated to administration of IRX-2 460 Units/day in combination with cyclophosphamide and durvalumab as Dose Level 2. If 2 of 6 patients have DLTs, stop accrual and re-evaluate. In the next safety phase, six patients at IRX-2 460 Units/day in combination with cyclophosphamide and durvalumab will be enrolled and treated sequentially (at least 1 week apart). If DLT occurs in less than 2 of 6 patients during the first 6 weeks of treatment, enrollment can continue in the dose expansion phase at Dose Level 2. If DLT is observed in 2 of 6 patients, accrual will be stopped and Dose Level 1 will resume in the dose expansion phase.

14 patients will be enrolled at the recommended dose level from the dose finding phase for a total enrollment of 20 patients; however, investigators will replace patients with any missing tumor sample collection and continue enrollment until there are at least 20 pre- and post-treatment paired tumors (i.e. minimum 2 of 3 tumors per patient). The 6 patients treated at the recommended dose in the dose finding phase of the study will be counted as a part of the dose expansion patient population,

Phase 1 and Phase 2: 1500 mg every 4 weeks (Q4wks).

Phase 1 and Phase 2 - Every 12 weeks - IRX-2 Regimen:

Cyclophosphamide 300 mg/m\^2 - intravenously.

IRX-2: 460 units daily (4 injections of 115 units).

IRX-2 Regimen

Christine Chung, M.D.

The purpose of this study is to see if the IRX-2 regimen and Durvalumab, will have a tolerable safety profile and will increase the intratumoral immune profile compared with the pretreatment tumors.

Study Population:

Patients with histologically or cytologically confirmed recurrent or metastatic squamous cell carcinoma of oral cavity, oropharynx, paranasal sinuses, hypopharynx, or larynx that is not amenable to local therapy with curative intent. Squamous cell carcinoma of unknown primary in cervical lymph node can be included only if p16 status is positive.

IRX-2 Regimen and Durvalumab, for Incurable H&N Squamous Cell Carcinoma

A Phase 1b Trial of the IRX-2 Regimen and Durvalumab (MEDI4736), in Patients With Incurable Head and Neck Squamous Cell Carcinoma

MTD of combination of the IRX-2 regimen and durvalumab as outlined in treatment arm.

Response to combination of the IRX-2 regimen and durvalumab . Objective response will be documented using standard Response Evaluation in Solid Tumors (RECIST) criteria.

Progression Free Survival of IRX-Dura treatment participants at six months. Progression free survival is defined as the time from Day 1 of treatment to evidence of progression. Progression will be defined by RECIST v 1.1.

Median Progression Free Survival of IRX-Dura treatment participants. Progression free survival is defined as the time from Day 1 of treatment to evidence of progression. Progression will be defined by RECIST v 1.1.

Median Overall Survival of IRX-Dura treatment participants. OS: The length of time from the start of treatment that participants are still alive.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
First Line Weekly Chemo/Immunotherapy for Metastatic Head/Neck Squamous Cell Carcinoma Patients	NCT04858269	Head Neck Cance... Metastatic Squa... Oral Cavity Squ... Oropharynx Squa... Hypopharynx Squ... Larynx Squamous...	Pembrolizumab Carboplatin Paclitaxel	18 Years -	Wake Forest University Health Sciences
IRX-2 Regimen and Durvalumab, for Incurable H&N Squamous Cell Carcinoma	NCT03381183	Squamous Cell C... Squamous Cell C... Metastatic Squa... Oral Cavity Squ... Oropharynx Squa... Paranasal Sinus... Hypopharynx Squ... Larynx Squamous...	Durvalumab IRX-2 Regimen	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
First Line Weekly Chemo/Immunotherapy for Metastatic Head/Neck Squamous Cell Carcinoma Patients	NCT04858269	Head Neck Cance... Metastatic Squa... Oral Cavity Squ... Oropharynx Squa... Hypopharynx Squ... Larynx Squamous...	Pembrolizumab Carboplatin Paclitaxel	18 Years -	Wake Forest University Health Sciences
IRX-2 Regimen and Durvalumab, for Incurable H&N Squamous Cell Carcinoma	NCT03381183	Squamous Cell C... Squamous Cell C... Metastatic Squa... Oral Cavity Squ... Oropharynx Squa... Paranasal Sinus... Hypopharynx Squ... Larynx Squamous...	Durvalumab IRX-2 Regimen	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
First Line Weekly Chemo/Immunotherapy for Metastatic Head/Neck Squamous Cell Carcinoma Patients	NCT04858269	Head Neck Cance... Metastatic Squa... Oral Cavity Squ... Oropharynx Squa... Hypopharynx Squ... Larynx Squamous...	Pembrolizumab Carboplatin Paclitaxel	18 Years -	Wake Forest University Health Sciences

Spots Global Cancer Trial Database for larynx squamous cell carcinoma