Radiotherapy With Cisplatin vs. Docetaxel-cetuximab in HNSCC: ERCC1 Biomarker Enrichment and Interaction Design

NCT02128906 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: HCC 13-056
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn which chemotherapy combination may be more effective in treating locally advanced head and neck squamous cell carcinoma (HNSCC). The side effects of these combinations will also be studied. This study treatment consists of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy. For study chemotherapy, patients will be randomized between cisplatin or the combination of docetaxel and cetuximab. Subjects will be stratified depending on HPV status and the presence of ERCC-1 \[4F9\] in the tumor prior to randomization. The study will evaluate cisplatin vs. docetaxel-cetuximab in the overall population, and test which radiation and chemotherapy combination works best in relationship to how much ERCC-1 \[4F9\] is expressed in a tumor.

Conditions

Squamous Cell Carcinoma

Keywords

ERCC1; oropharynx; larynx; hypopharynx; p16; radiotherapy; docetaxel; cetuximab; cisplatin; EGFR; head and neck

Outcome Measures

Primary Outcomes (1)

• Time To Progression (TTP)

  Time To Progression is the duration of time from date of study entry until the first appearance of new metastatic lesions or objective tumor progression in patients with increased tumoral ERCC1 expression. Progression is defined per RECIST v1.1 as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

  Up to 5 years

Secondary Outcomes (15)

• Time to progression (TTP)

  Up to 5 years

• Local Control Rate (LRC)

  Up to 5 years

• Rate of distant metastases

  Up to 5 years

• Validation candidate cutpoint

  Up to 5 years

• Response per RECIST 1.1

  Up to 5 years

Study Arms (2)

Cisplatin-IMRT

ACTIVE COMPARATOR

Cisplatin 40 mg/m2 weekly x 7; IMRT: once daily, M-F, 7 weeks (70 Gy)

Drug: Cisplatin; Radiation: IMRT

Docetaxel-Cetuximab-IMRT

ACTIVE COMPARATOR

Docetaxel 15 mg/m2 weekly x 7; Cetuximab 400 mg/m2 load, one week prior to IMRT; Cetuximab 250 mg/m2 weekly x 7; IMRT: once daily, M-F, 7 weeks (70 Gy)

Radiation: IMRT; Drug: Docetaxel; Drug: Cetuximab

Interventions

Cisplatin DRUG

Cisplatin 40 mg/m2 weekly x 7

Also known as: Platinol

Cisplatin-IMRT

IMRT RADIATION

IMRT: once daily, M-F, 7 weeks (70 Gy)

Cisplatin-IMRT; Docetaxel-Cetuximab-IMRT

Docetaxel DRUG

Docetaxel 15 mg/m2 weekly x 7

Also known as: Taxotere

Docetaxel-Cetuximab-IMRT

Cetuximab DRUG

Cetuximab 400 mg/m2 load, one week prior to IMRT Cetuximab 250 mg/m2 weekly x 7

Also known as: Erbitux

Docetaxel-Cetuximab-IMRT

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed squamous cell carcinoma, undifferentiated carcinoma, or poorly differentiated carcinoma of the oropharynx, larynx, or hypopharynx with no evidence of distant metastasis. Biopsy sampling of primary tumor with pathology report documenting diagnostic tissue type is required.
• Patients must have stage III, IVa or IVb disease as determined by imaging studies and complete head and neck exam. Staging evaluation should be in accordance with the American Joint Committee on Cancer Staging Manual, 7th edition.
• Patients with oropharyngeal squamous cell carcinoma may have p16(+) or p16(-) disease; in these patients, p16 status must be known prior to randomization. Assessment of p16 status may occur locally or centrally. Note: The definition of p16(+) disease is diffuse nuclear and cytoplasmic staining in ≥ 70% of tumor cells.
• Patients must be untreated with curative-intent surgery for current diagnosis of Stage III, IVa, or IVb disease. Diagnostic biopsy of primary tumor and/or nodal sites is permitted.
• Diagnostic simple tonsillectomy is permitted, provided patient has RECIST-measurable residual tumor and/or nodal disease.
• Patients with a second HNSCC primary tumor are eligible for this study, provided more than 2 years have elapsed since the first diagnosis of HNSCC, the original tumor was managed with surgery only (no adjuvant chemotherapy/radiotherapy), and has not recurred.
• Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible.
• No prior systemic treatment (chemotherapy or biologic/molecular targeted therapy) or radiation treatment for head and neck cancer.
• Patients may have received chemotherapy or radiation for a previous, curatively treated non-HNSCC malignancy, provided at least 2 years have elapsed.
• Patients must be untreated with radiation above the clavicles.
• Patients with a history of curatively-treated non-HNSCC malignancy must be disease-free for at least 2 years except for carcinoma-in-situ of cervix, non-melanomatous skin cancer, or T1-2, N0, M0 resected differentiated thyroid carcinoma.
• Diagnostic primary tumor tissue must be available for ERCC1 staining
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 (See Appendix 8)
• Age ≥ 18
• Patients must have measurable disease according to RECIST 1.1

Sponsors & Collaborators

• Christopher Wilke: lead

Study Sites (1)

UPMC Hillman Cancer Center - Radiation Oncology

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Laryngeal Diseases

Interventions

Cisplatin; Docetaxel; Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christopher T Wilke, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samantha Demko, RN

CONTACT

412-647-9015; albesl@upmc.edu

Brieana Marino, MS

CONTACT

412-647-8258; rowlesbm@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Radiation Oncologist

Study Record Dates

• First Submitted: April 29, 2014
• First Posted: May 1, 2014
• Study Start: December 23, 2013
• Primary Completion (Estimated): December 16, 2031
• Study Completion (Estimated): December 16, 2031
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)