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

NCT03174275 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: LCCC 1621
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Oropharynx Cancer; Larynx Cancer; Lip Cancer; Esophageal Cancer; Carcinoma, Squamous Cell; Oral Cancer

Keywords

squamous cell carcinoma of the head and neck (SCCHN); durvalumab; neoadjuvant induction; post-operative treatment

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  After surgery (approximately 8-12 weeks after start of study treatment)

Secondary Outcomes (5)

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

  1-4 weeks post induction chemotherapy

• Percent of Patients Who Have a Change in Estimated Risk Level

  After surgery (approximately 8-12 weeks after start of study treatment)

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

  5 years

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

  5 years

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

  90 days after the last dose of study treatment

Other Outcomes (2)

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

  8-12 weeks after the last dose of study treatment

• 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).

  8-12 weeks after the last dose of study treatment

Study Arms (3)

Low Risk

EXPERIMENTAL

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

Drug: Durvalumab; Drug: Carboplatin; Drug: Nab-paclitaxel; Procedure: Surgical resection

Medium Risk

EXPERIMENTAL

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.

Drug: Durvalumab; Drug: Carboplatin; Drug: Nab-paclitaxel; Drug: Cisplatin; Procedure: Surgical resection; Radiation: IMRT

High Risk

EXPERIMENTAL

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.

Drug: Durvalumab; Drug: Carboplatin; Drug: Nab-paclitaxel; Drug: Cisplatin; Procedure: Surgical resection; Radiation: IMRT

Interventions

Carboplatin DRUG

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

Also known as: Paraplatin

High Risk; Low Risk; Medium Risk

Nab-paclitaxel DRUG

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.

Also known as: Abraxane

High Risk; Low Risk; Medium Risk

Cisplatin DRUG

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.

High Risk; Medium Risk

Surgical resection PROCEDURE

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

High Risk; Low Risk; Medium Risk

IMRT RADIATION

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

Also known as: Intensity-modulated radiation therapy

High Risk; Medium Risk

Durvalumab DRUG

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

Also known as: MEDI4736

High Risk; Low Risk; Medium Risk

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previously untreated, histologically proven, surgically resectable primary squamous cell carinoma of the head and neck, stage III or IV (HPV positive or negative non-metastatic disease). SCCHN of unknown primary is excluded. SCCHN of the oral cavity is allowed\*. Unambiguously squamous Epstein-Barr virus (EBV)-negative nasopharynx cancer will be excluded nor will unambiguously squamous cancers of the skull base that are clearly surgically resectable and clearly squamous. Squamous skin cancer occurring in the head/neck region will not be eligible nor will EBV+positive nasopharynx cancer. (\*Note: Induction chemotherapy is not considered standard therapy for SCCHN of the oral cavity and participation on this trial will lead to a delay in time to definitive, potentially curative therapy i.e., surgery).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Measurable disease as per RECIST 1.1
• Age greater than or equal to 18 at time of study entry
• Adequate bone marrow function as demonstrated by:
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
• Hgb \> 10 g/dL (use of transfusion to reach this threshold prior to study initiation is acceptable)
• Platelet count ≥ 100,000/mm3
• Adequate hepatic and renal function as demonstrated by:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN);
• Total serum bilirubin ≤1.5 x ULN
• Creatinine clearance (CrCL) \> 40 mL/min as measured via Cockcroft-Gault
• Males: Creatinine CL (mL/min) = (Weight (kg) x (140 - Age))/(72 x serum creatinine (mg/dL))
• Females: Creatinine CL (mL/min) = (Weight (kg) x (140 - Age))/(72 x serum creatinine (mg/dL)) x 0.85
• Negative serum β human chorionic gonadotropin (β-hCG) pregnancy test within 72 hours of day 1 of induction chemotherapy in women of child-bearing potential.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to staff at the study site) or previous enrollment in the present study.
• Any metastatic disease.
• Known history of previous clinical diagnosis of tuberculosis.
• History and/or confirmed pneumonitis.
• Low-risk HPV+ disease of the oropharynx, defined as meeting all of the following criteria:
• Patients with known HPV+ by fluorescence in situ hybridization (FISH) and/or p16
• Smoking history ≤ 10 pack years
• Stage T1-2N0-2b, T3N0
• Not considered eligible for any of the chemotherapy agents included in the induction regimen.
• Current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment).
• Major surgery within 28 days prior to day 1 of study treatment from which the patient has not completely recovered.
• Receiving any investigational agent currently or within 28 days or 5 half-lives of Day 1 of treatment on this study, whichever is shorter.
• Active, serious infection, medical, or psychiatric condition that would represent an inappropriate risk to the patient or would likely compromise achievement of the primary study objective, including unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction ≤ 6 months prior to study entry.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis, Crohn's disease\], diverticulitis with the exception of a prior episode that has resolved or diverticulosis, celiac disease, irritable bowel disease, or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener's syndrome \[granulomatosis with polyangiitis\]; myasthenia gravis;; rheumatoid arthritis; hypophysitis, uveitis; etc) within the past 2 years prior to the start of treatment. \[Note: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded\]
• Known mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction. (Note that ECG is not required for study entry and is not part of study procedures).

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• AstraZeneca: collaborator
• Celgene: collaborator

Study Sites (2)

Lineberger Comprehensive Cancer Center at University of North Carolina Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trial

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Mouth Neoplasms; Oropharyngeal Neoplasms; Laryngeal Neoplasms; Lip Neoplasms; Esophageal Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

durvalumab; Carboplatin; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Cisplatin; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Neoplasms by Site; Mouth Diseases; Stomatognathic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Lip Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Dr. Jared Weiss
• Organization: University of North Carolina Lineberger Comprehensive Cancer Center

jared_weiss@med.unc.edu

+1 919-843-7718

Study Officials

• Jared Weiss, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2017
• First Posted: June 2, 2017
• Study Start: December 19, 2017
• Primary Completion: February 2, 2022
• Study Completion (Estimated): February 2, 2027
• Last Updated: February 23, 2026
• Results First Posted: February 8, 2023

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)