Carboplatin, Nab-Paclitaxel, Durvalumab Before Surgery and Adjuvant Therapy in Head and Neck Squamous Cell Carcinoma

Esophageal Cancer Clinical Trial

Official title: Multimodality Therapy With Induction Carboplatin/Nab-Paclitaxel/Durvalumab Followed by Surgical Resection and Risk-adapted Adjuvant Therapy for the Treatment of Locally-Advanced and Surgically Resectable Squamous Cell Carcinoma of the Head and Neck

Status Active, not recruiting

Clinical Trial Summary

Participants in this study have a type of cancer called squamous cell carcinoma of the head and neck (SCCHN). Their SCCHN has spread around the area where the cancer first started. This is called locally-advanced SCCHN. These participants are eligible for surgery.

Previous research with a similar therapy regimen resulted in high rates of cancer shrinkage, high rates of avoiding radiation and its side effects, high cure rate and good quality of life. Radiation can be very toxic. The purpose on this study is to try to avoid radiation. If the participants are not on this study they would be receiving radiation as it is standard treatment of their cancer. In the last study with a similar regimen, about a third of cancers had a pathologic complete response with the first part of the study. This means that the chemotherapy had killed the cancer. The investigators are trying to improve the regimen further with a goal of increasing this rate of complete response to the first part of therapy. The investigators also hope that by improving results in the first part, that more people will be cured and that long term quality of life (especially speech and swallowing) will be improved, both compared to standard therapies and to the last study. Doctors do not know how this therapy will effect the participants. There is no guarantee that this study will benefit the participants.

The prior study used a combination of chemotherapy consisting of carboplatin, paclitaxel and a third targeted anti-cancer drug. In this study the investigators are testing the combination of carboplatin, nano-albumin bound paclitaxel and durvalumab. Nano-albumin bound paclitaxel has been shown to be more active against other types of squamous cancers than regular paclitaxel. It is FDA approved for squamous lung cancer, but experimental for head and neck cancer. Durvalumab is an experimental drug that uses the body's own immune system to fight the cancer. Doctors hope that combining Durvalumab with 2 chemotherapy drugs will be effective in treating SCCHN. Durvalumab on its own has been studied in patients with SCCHN and initial results have shown that some subjects' cancer has responded to it.

The purpose of this study is to test a combination of chemotherapy to hopefully both increase the number of subjects that respond to therapy while also decreasing the number of side effects that subjects experience.

Clinical Trial Description

STUDY OBJECTIVES

Primary Objective:

Estimate the pathologic complete response rate (pCRR) after induction chemotherapy with carboplatin, nab-paclitaxel, and durvalumab in previously untreated stage III and IV SCCHN amenable to surgical resection

Secondary Objectives:

• Report the clinical complete response rate (cCRR) and clinical response rate (cRR) following induction chemotherapy

• Estimate the percent of patients who have a change in estimated risk level. Prior to induction, this will be assessed clinically (by imagining and physical exam). Post induction, this will be assessed by surgical pathology report

• Estimate the overall survival (OS) and progression free survival (PFS) associated with 3 part therapy consisting of induction chemotherapy, surgery and risk-adapted use of chemoradiation

• Characterize the toxicity profile associated with both induction therapy and total 3 part therapy consisting of induction chemotherapy, surgery and risk-adapted use of chemoradiation

Translational/Exploratory Objectives:

• Correlative studies will evaluate cellular correlates of response and changes in the tumor microenvironment across therapy

• Explore correlation between measures of clinical response to induction chemotherapy and long term outcomes (PFS and OS) and compare them to pathologic measures of response (pCRR)

PROCEDURES This is a single-arm, nonrandomized phase II trial consisting of 3 parts. After informed consent and screening, pre-induction, risk levels will be assessed clinically, by a combination of physical exam and imaging.

Part 1: All patients will then receive 6 weeks of induction chemotherapy in Part 1 comprised of weekly cycles of carboplatin and nab-paclitaxel for 6 cycles in combination with durvalumab administered once every two weeks for 5 cycles (Day 1 of the weeks 1, 3, 5, 7, and 9).

Part 2: Within a 1-4 the week window post induction, tumor imaging will be followed by surgical resection.

Part 3: After surgery, patients will be stratified into one of 3 risk categories based on their disease pathology, assigned a treatment group based on their risk. Low risk patients with receive durvalumab once every two weeks for 3 cycles, while medium risk or high risks groups will receive concurrent chemoradiation therapy followed by durvalumab once every two weeks for 3 cycles.

Follow up After completion of study therapy (which will vary by study arm) patients will be evaluated every three months during follow up for progression over a period of 18 months. Each follow up visit will include physical examination, CT or MRI imaging of the neck. Chest imaging will be obtained (or not) as indicated by standard of care. After the first 18 months, patients will be followed-up per standard of care, with documentation in the case report form (CRF) limited to progression and survival noted at their standard of care visits. If a patient should move away or otherwise be lost to in-person follow up but is amenable to telephone follow up, this will be permitted during the standard of care follow up period. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Cancer
• Laryngeal Neoplasms
• Larynx Cancer
• Lip Cancer
• Lip Neoplasms
• Mouth Neoplasms
• Oral Cancer
• Oropharyngeal Neoplasms
• Oropharynx Cancer
• Squamous Cell Carcinoma of Head and Neck

• NCT number: NCT03174275
• Study type: Interventional
• Source: UNC Lineberger Comprehensive Cancer Center
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 19, 2017
• Completion date: February 2, 2027