Safety Study of Afatinib and Postoperative Radiation Therapy to Treat Head and Neck Cancer

NCT01783587 | Completed Phase 1 DMC

• 1 other identifier: 12-267
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is a Phase I clinical trial. Phase I clinical trials test the safety of an investigational drug. Phase I studies also try to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use and the side effects it may cause. Afatinib has been studied in other clinical trials of participants with head and neck cancer, lung cancer, and breast cancer. This dose of Afatinib has also been studied in other research studies. This is the first clinical trial to study Afatinib in combination with Radiation Therapy. The purpose of this study is to determine the safest dose of Afatinib when given in combination with Radiation Therapy or in combination with Radiation Therapy and chemotherapy for head and neck cancer. Afatinib is a drug that may stop cancer cells from growing abnormally. This drug works by blocking multiple proteins known to play a role in the growth of cancer cells. Information from laboratory research studies suggests that this drug may help to make head and neck cancer cells more sensitive to Radiation Therapy. The other therapy in this research study is Radiation Therapy or Radiation Therapy plus a chemotherapy drug called Docetaxel. After surgery, Radiation Therapy and chemotherapy is the standard treatment if you have high risk disease. "High risk disease" means that without additional therapy, there is a high risk that the disease may return. In this study, participants with high-risk disease will receive Radiation Therapy and Docetaxel and Afatinib. "Intermediate risk" means that there is an intermediate risk that the disease may return. Radiation Therapy alone is the standard treatment approach for intermediate risk cancer. In this study, participants with intermediate risk disease will receive Radiation Therapy and Afatinib.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (1)

• The presence or absence of a dose-limiting toxicity at a given dose-level of afatinib.

  All participants who receive any amount of study drug will be evaluable for toxicity. The primary outcome measure is the incidence of a physician-assessed dose-limiting toxicity (DLT) at a given dose-level of afatinib. Participants will be assessed for a DLT at least once per week during the course of therapy, including the one-week afatinib lead-in period and the 6-7 weeks of radiation therapy. DLT's are defined as the incidence of a severe or life-threatening toxicity (grade 3-4) as defined by the Common Terminology Criteria for Adverse Events Versions 4 (CTCAEv.4) or any afatinib-related toxicity requiring a dose reduction occurring during treatment with afatinib and radiation therapy +/- docetaxel. Participants will continue to be assessed for adverse events for 12 weeks after the completion of therapy.

  7 weeks

Study Arms (2)

High Risk Group

EXPERIMENTAL

Dose escalation of afatinib + docetaxel + radiation therapy

Drug: Afatinib; Drug: Docetaxel; Radiation: Radiation Therapy

Intermediate Risk Group

EXPERIMENTAL

Dose escalation of afatinib + radiation therapy

Drug: Afatinib; Radiation: Radiation Therapy

Interventions

Docetaxel DRUG

15 mg/m2, given intravenously once per week

Also known as: Taxotere

High Risk Group

Radiation Therapy RADIATION

Daily, Monday-Friday, for six to seven weeks

High Risk Group; Intermediate Risk Group

Afatinib DRUG

Taken orally once per day

Also known as: Gilotrif

High Risk Group; Intermediate Risk Group

Eligibility Criteria

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

You may qualify if:

• Histologically proven diagnosis of squamous cell carcinoma of the head and neck
• Pathology from the primary surgery must be reviewed and finalized at either the Dana-Farber Cancer Institute/Brigham \& Women's Hospital or the pathology department at any participating institution
• Status post gross total resection with curative intent
• Primary tumor site: oral cavity, oropharynx, larynx, hypopharynx
• Disease must be defined as either high-risk or intermediate risk
• Definition of high-risk: Any of the following high-risk features: positive margins (defined as tumor at ink), extracapsular extension of lymph node, gross T4a or T4b primary tumor, any lymph node ≥ 6cm (N3)
• Definition of intermediate-risk: Absence of any high-risk features AND any one of the following intermediate risk features: Two or more positive lymph nodes involved with squamous cell carcinoma, single lymph node \>3cm and \<6cm, perineural invasion, lymphovascular invasion, Level IV or level V involvement of oral cavity or oropharyngeal tumors, or T2 oral cavity tumor with \>5mm depth of invasion

You may not qualify if:

• Prior anti-epidermal growth factor (EGF) or anti-Human Epidermal Growth Factor Receptor-2 (HER2) therapy
• Prior radiation therapy to the head and neck
• Pregnant or breastfeeding
• Distant metastases
• Receiving other study agents
• History of interstitial lung disease
• Symptomatic peripheral neuropathy
• Active or prior malignancy except non-melanoma skin cancer
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to afatinib or docetaxel
• Cardiac left ventricular dysfunction
• Uncontrolled intercurrent illness
• HIV positive on combination antiretroviral therapy

Sponsors & Collaborators

• National Comprehensive Cancer Network: collaborator
• Dana-Farber Cancer Institute: lead

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mount Sinai Medical Center/Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Afatinib; Docetaxel; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Therapeutics

Study Officials

• Danielle Margalit, MD, MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 30, 2013
• First Posted: February 5, 2013
• Study Start: February 1, 2013
• Primary Completion: November 20, 2017
• Study Completion: June 1, 2018
• Last Updated: March 25, 2026

Record last verified: 2026-03

Locations

US (3)