A Study of Neoadjuvant Bio-C/T Followed by Concurrent Bio-R/T in High-risk Locally Advanced Oral Squamous Cell Carcinoma

A Phase II Study of Neoadjuvant Bio-chemotherapy With Cetuximab, Paclitaxel, and Cisplatin (CPC) Followed by Cetuximab-based Concurrent Bio-radiotherapy in High-risk Locally Advanced Oral Squamous Cell Carcinoma (OSCC)

Surgical resection followed by concurrent chemoradiotherapy is considered as the standard of care for locally advanced OSCC (LAOSCC). Although the treatment could provide prompt local control, but it is also associated with high incidence of distant failure. Systemic chemotherapy given either before (neoadjuvant) or after (adjuvant) definitive local treatment has been extensively evaluated to improve the clinical outcome in LAOSCC. Regimens of taxane/cisplatin-based combinations have been shown to improve the treatment outcome of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) in neoadjuvant setting. Recently, cetuximab (Erbitux®), a monoclonal antibody against epidermal growth factor receptor (EGFR), has also been proven to be an efficient agent for advanced and/or refractory HNSCC with acceptable toxicity profiles. In current study, we shall evaluate the feasibility, efficacy and safety of a triplet bio-chemotherapy consisting of cetuximab, paclitaxel, and cisplatin followed by cetuximab-based concurrent bio-radiotherapy (CBRT) in patients with LAOSCC.

Study Overview

• Status: Completed
• Conditions: Oral Cancer
• Intervention / Treatment: Drug: Cetuximab,Paclitaxel,Cisplatin

Detailed Description

Patients with high-risk, locally advanced (TxN2b~3 or T4N0~3, M0) OSCC will be eligible. To detect an interested objective response rate (p1) of 80% versus a non-interested response (p0) rate of 60%, with an α and 1-β of 0.05 and 0.2, respectively (two-sided test), including the estimated dropout rate of 10%, a total of 47 patients will be recruited.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan
    • National Health Research of Institutes, Taiwan Cooperative Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. High-risk, locally advanced (TxN2b~3 or unresectable T4, M0) OSCC
2. Histologically confirmed squamous cell carcinoma
3. Performance status: Eastern Cooperative Oncology Group performance status (ECOG) 0-1
4. age 18 years or older, less than 70 years of age
5. Having signed informed consent
6. Measurable disease by CT or MRI
7. Adequate hematologic, hepatic and renal function

Exclusion Criteria:

1. Prior radiotherapy for targeted lesions, chemotherapy, EGFR pathway targeting therapy
2. Prior surgery for cancer except for the purpose of diagnostic biopsy
3. Concomitant active 2nd malignancies or disease-free of malignancies < 3 years before the study except adequately treated in situ cervical cancer, or non-melanoma skin cancer
4. Concomitant anticancer therapies within the past 28 days
5. Severe cardiopulmonary diseases and other systemic disease under poor control
6. Uncontrolled chronic neuropathy
7. Women who are positive of pregnancy, or in breast-feeding
8. Known allergy to any study treatment
9. Legal incapacity
10. Significant disease which, in the investigator's opinion, would exclude the patient from the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: open label; an open-labelled, single-arm	Drug: Cetuximab,Paclitaxel,Cisplatin; Cetuximab 500 mg/m2 iv infusion (120 min for the 1st infusion, 90 min for the 2nd , and 60 min for the subsequent) Paclitaxel 120 mg/m2 3-hour iv infusion Cisplatin 50 mg/m2 2-hour iv infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint is the overall response rate after completion of the assigned treatment.	18 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Secondary endpoints include the response rate after neoadjuvant therapy, progression-free survival, overall survival, biomarker prediction, and toxicity.	>2 years

Collaborators and Investigators

• Sponsor: National Health Research Institutes, Taiwan
• Collaborators: China Medical University Hospital; Chang Gung Memorial Hospital; National Cheng-Kung University Hospital; Changhua Christian Hospital; Chi Mei Medical Hospital
• Investigators: Principal Investigator: J Y Chang, M.D., National Health Research of Institutes

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (ACTUAL): July 1, 2011
• Study Completion (ACTUAL): November 1, 2013

Study Registration Dates

• First Submitted: July 3, 2009
• First Submitted That Met QC Criteria: July 6, 2009
• First Posted (ESTIMATE): July 7, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): May 4, 2016
• Last Update Submitted That Met QC Criteria: May 3, 2016
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: biomarker; oral squamous cell carcinoma; neoadjuvant bio-chemotherapy; concurrent bio-radiotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Mouth Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Paclitaxel; Cisplatin; Cetuximab
• Other Study ID Numbers: T1309; EMR62202-845