A Study of Tongue Conservation Surgery for Oral Tongue Cancer

A Phase II Study of Tongue Conservation Surgery for Advanced Oral Tongue Cancer: Induction Chemotherapy, Followed by Tongue Conservation Surgery and Postoperative Chemoradoitherapy

This is an open-label, non-comparative phase II clinical trial to assess efficacy and safety of tongue conservation treatment with sequential induction chemotherapy, tongue conservation surgery and postoperative concurrent chemoradiotherapy (CCRT) in patients with advanced oral tongue cancer.

Study Overview

• Status: Terminated
• Conditions: Surgery; Chemotherapy Effect; Tongue Cancer
• Intervention / Treatment: Drug: Induction chemotherapy; Procedure: Tongue conservation surgery; Radiation: postoperative CCRT

Detailed Description

Surgical resection remains the most important component of standard treatment for oral tongue cancer, but may lead to profound functional impacts not effectively compensated by reconstruction surgery. The volume of tongue resection remains one key factor for the post-treatment deterioration of the functional outcomes and quality of life in large oral tongue cancer. Primary chemoradiotherapy without surgical resection has not been accepted for oral tongue cancer because of the concerns about possible poorer response and sequelae. Breast conservation treatment, by the sequential use of induction chemotherapy (ICT), limited surgical resection and chemoradiotherapy, has become a standard treatment for human breast cancer of various stages. However, similar tongue conservation treatment for advanced oral tongue cancer has not been studied in trials. Based on these data, it will be reasonable, in locally advanced (> 3 cm) resectable oral tongue cancers, to test whether ICT followed by tongue conservation surgery and postoperative CCRT can safely enhance the possibility of tongue conservation with improved post-treatment functions.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with histological proof of squamous cell carcinoma of oral tongue
• b. cT2-4, N0-2,M0, by clinical or radiographic examinations
• Either mandibulotomy, mandibulectomy or flap reconstruction is required by standard surgical planning
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Between 20 and 70 years of age
• Adequate hematopoietic function as defined below:

Hemoglobin >= 10g/dl Absolute neutrophil count (ANC) >= 1,500/µL Platelets >= 100,000/µL

• Adequate organ function as defined below:

Total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine <= 1.5 x upper limit of normal Creatinine clearance > 50 ml/min

• Signed study-specific consent form prior to study entry

Exclusion Criteria:

• Patients received gross oral tongue tumor resection before evaluation
• Primary subsites other than oral tongue
• Histologic diagnosis other than squamous cell carcinoma
• Patient with synchronous primary cancers (within 6 months)
• Clinical or radiographic findings as below:

T1 tumors Gross invasion to mandible, tonsil or >1/3 base of tongue N3 disease or distant metastasis (M1)

• Prior head and neck chemotherapy or radiotherapy
• Prior esophageal cancer history
• Active cardiac disease defined as: unstable angina, uncontrolled arrhythmia, myocardial infarction within 6 months.
• Severe chronic obstructive pulmonary disease (COPD) requiring ≥ 3 hospitalizations over the past year
• Mental status not fit for clinical trial.
• Pregnant or breast feeding women, or women of child-bearing potential unless using a reliable and appropriate contraceptive method.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Induction chemotherapy; Induction chemotherapy will be given every 21 days, with the DCU regimen, followed by tongue conservation surgery, and postoperative CCRT as indicated.

Drug: Induction chemotherapy; All eligible subjects will receive ICT with DCU regimen every 21 days as follows: Docetaxel 36 mg/m2 intravenous infusion over 1 hr, followed by Cisplatin 30 mg/m2 intravenous infusion over 1 hr, on day 1 and day 8, Oral tegafur/uracil 300 mg/m2/day plus leucovorin 90 mg/day on days 1 - 14; Procedure: Tongue conservation surgery; Surgical excision of residual oral tongue tumor will be performed in 3-4 weeks after the start of the last cycle of ICT. Neck dissection will also be done as indicated.; Radiation: postoperative CCRT; Post-op CCRT will be started 4-6 weeks after surgery, with regimen as follows: Radiotherapy in 2 Gy once-daily fraction size, Monday to Friday, with dose up to 60 Gy (total of 30 fractions); Cisplatin 25 mg/m2 intravenously for 4 hours every week a cycle to total 6 cycles; Tegafur/uracil (UFUR) 200 mg po bid for whole course of radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Response to induction chemotherapy	2 weeks after completion of the last cycle of induction chemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tongue conservation surgery feasibility rates	Feasibility of tongue conservation surgery	the date of surgery
Pathological response of induction chemotherapy	Pathological evaluation of rediual tumor status	2 weeks after surgery
Longitudinal quality of life (QOL)	Evaluation of QOL with the EORTC-C30 and HN35 QOL questionnaires	Date of recruitment, 2 weeks after ICT completion, 3 months after treatement copletion, 1 year after treatment completion
Oncologic results	Disease specific survival	5 years after treatment completion

Collaborators and Investigators

• Sponsor: Taipei Veterans General Hospital, Taiwan

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2011
• Primary Completion (Actual): January 27, 2016
• Study Completion (Actual): January 4, 2017

Study Registration Dates

• First Submitted: May 17, 2017
• First Submitted That Met QC Criteria: May 18, 2017
• First Posted (Actual): May 22, 2017

Study Record Updates

• Last Update Posted (Actual): May 30, 2017
• Last Update Submitted That Met QC Criteria: May 24, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Mouth Neoplasms; Tongue Diseases; Tongue Neoplasms
• Other Study ID Numbers: 201009018MB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• product manufactured in and exported from the U.S.: No