Neoplasms

Digestive System Diseases

All Conditions

Mouth and Tooth Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Esophageal Neoplasms

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Mouth Neoplasms

Laryngeal Diseases

Oropharyngeal Neoplasms

Laryngeal Neoplasms

Lip Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Mouth Diseases

Stomatognathic Diseases

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Pharyngeal Diseases

Otorhinolaryngologic Diseases

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Esophageal Cancer

Oral Cancer

Lip and Oral Cavity Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Cisplatin

Durvalumab

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Part 1- Patients receive 6 weeks of induction chemotherapy comprised of weekly cycles of carboplatin dosed to an Area Under the Curve (AUC2) and nab-paclitaxel 100 mg/m2 X 6 cycles in combination with durvalumab 750 mg administered once every two weeks for 5 cycles (D1 of weeks 1, 3, 5, 7, and 9).

Part 2- Within a 2-6 week window post induction, tumor imaging will be followed by surgical resection.

Part 3- patients receive adjuvant durvalumab (750 mg) once every two weeks x 3 cycles

Part 1- Patients receive 6 weeks of induction chemotherapy comprised of weekly cycles of carboplatin dosed to an Area Under the Curve (AUC2) and nab-paclitaxel 100 mg/m2 X 6 cycles in combination with durvalumab 750 mg administered once every two weeks for 5 cycles (D1 of weeks 1, 3, 5, 7, and 9).

Part 2- Within a 2-6 week window post induction, tumor imaging will be followed by surgical resection.

Part 3- patients receive ipsilateral involved field radiation concurrent with weekly cisplatin 30mg/m2. Once chemoradiotherapy is complete these patients will receive durvalumab 750 mg every two weeks for 3 cycles.

Part 1- Patients receive 6 weeks of induction chemotherapy comprised of weekly cycles of carboplatin dosed to an Area Under the Curve (AUC2) and nab-paclitaxel 100 mg/m2 X 6 cycles in combination with durvalumab 750 mg administered once every two weeks for 5 cycles (D1 of weeks 1, 3, 5, 7, and 9).

Part 2- Within a 2-6 week window post induction, tumor imaging will be followed by surgical resection.

Part 3- All patients will be treated with intensity modulation radiation therapy (IMRT) concurrent with weekly cisplatin 30mg/m2 or other standard of care chemoradiotherapy regimen.Once chemoradiotherapy is complete these patients will receive durvalumab 750 mg every two weeks for 3 cycles.

Subjects will receive durvalumab, 750 mg every 2 weeks by IV infusion over approximately 1 hour (± 5 minutes).

Carboplatin is commercially available and approved by the US FDA for use in patients with ovarian cancer.

Nab-paclitaxel is commercially available and approved by the US Food and Drug Administration (FDA) for use in patients with metastatic breast cancer, metastatic pancreatic cancer, and for the treatment of locally advanced or metastatic NSCLC.

Nab-paclitaxel

Cisplatin is commercially available and approved by the US Food and Drug Administration (FDA) for the treatment of advanced bladder, ovarian and testicular cancer. It has been widely studied in a variety of solid tumor types.

Surgical therapy will be at the discretion of the treating surgeon per standard of care.

Surgical resection

"involved field radiation" will refer to areas demonstrated to harbor disease on pathology, and not elective areas

IMRT

Jared Weiss, MD

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.

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.

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

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

Pre-treatment specimens will be studied for predictive markers of treatment response. Paired pre- and post-treatment specimens will be compared to assess for changes in the tumor micro-environment.

The pCRR was assessed via surgical pathology report. Pathologic complete response will require no viable cancer cells on the surgical pathology report after neoadjuvant treatment with carboplatin, nab-paclitaxel, and durvalumab. This study protocol requires the same neoadjuvant therapy and surgery for all subjects. The primary outcome measure is the complete pathologic response defined by the surgical pathology report and is unrelated to adjuvant therapy.

Clinical complete response rate and clinical response rate (CR + PR) associated with induction chemotherapy will be estimated using RECIST 1.1.

Risk level pre-induction will be based on physical examination and imaging and will be defined and documented in electronic Case Report Forms (eCRF) prior to the initiation of induction therapy. Post-induction risk level will be determined based on pathologic evaluation of surgical specimen.

PFS will be defined as the time from day 1 of study treatment until progression per RECIST 1.1

Overall survival will be defined as the time from day 1 of study treatment until death from any cause

Safety associated with both induction alone and with 3 part therapy consisting of induction chemotherapy, surgery and risk-adapted use of chemoradiation will be assessed via the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03)

AstraZeneca

Celgene

UNC Lineberger Comprehensive Cancer Center

This study protocol requires the same neoadjuvant therapy and surgery for all subjects. Adjuvant treatment is assigned based on the risk group. Adjuvant treatment arms were not randomized. Therefore, Adverse Events were reported based on the whole group.

All Subjects

All subjects received at least one dose of study treatment, from any of the arms (low risk, medium risk, and high risk). This study protocol requires the same neoadjuvant therapy and surgery for all subjects. Adjuvant treatment is assigned based on the risk group. Adjuvant treatment arms were not randomized. Therefore, baseline characteristics were reported based on the whole group.

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

This study protocol requires the same neoadjuvant therapy and surgery for all subjects. Adjuvant treatment is assigned based on the risk group. The primary outcome measure is the complete pathologic response that is defined by the surgical pathology report. Complete pathologic response is not related to adjuvant therapy.

Dr. Jared Weiss

Pathologic complete response was achieved

Pathologic complete response was not achieved

All subjects received neoadjuvant chemotherapy and underwent surgery, and histopathological analyses were completed.

Pathologic Complete Response

Subjects received treatment in 4 cancer centers in the United States.

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

Clinical Complete Response Rate and (cCRR) and Clinical Response Rate (cRR) Following Induction Chemotherapy

Percent of Patients Who Have a Change in Estimated Risk Level

Progression Free Survival (PFS) Associated With 3 Part Therapy Consisting of Induction Chemotherapy, Surgery and Risk-adapted Use of Chemoradiation

Overall Survival (OS) Associated With 3 Part Therapy Consisting of Induction Chemotherapy, Surgery and Risk-adapted Use of Chemoradiation

Toxicity Profile Associated With Both Induction Therapy and Total 3 Part Therapy Consisting of Induction Chemotherapy, Surgery and Risk-adapted Use of Chemoradiation

Cellular Correlates of Response and Changes in the Tumor Microenvironment Across Therapy

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).

Spots Global Cancer Trial Database for neoadjuvant induction