A Study of High-Risk Oral Cavity Cancer

Phase 2

Terminated

• Conditions: Oral Cavity Cancer
• Interventions: Drug: Cyclophosphamide, Dexamethasone; Drug: Thalidomide, Celebrex

• Registration Number: NCT00934739
• Lead Sponsor: National Health Research Institutes, Taiwan

Brief Summary

Objectives:

1. To study the effect of anti-angiogenesis therapy on reducing the recurrence of high-risk oral cavity cancer patients after curative local treatment.

2. To study the toxicity and compliance of post-operative anti-angiogenesis therapy

Study design:

This is a multi-center randomized controlled phase II/III two-stage study.

Study endpoints:

The primary endpoint is the tumor-free survival (primary and second primary malignancies) and the primary analysis is to compare the tumor-free survival between groups.

Detailed Description

Type and number of patients:

Patients with resectable oral cancer of clinical stage N2, 3 or skin-involved T4 will be enrolled.

Sample size at the first stage is 64 patients per group and the total sample size at the end of the second stage is 192 patients per group, assuming that the accrual rate/hazard rate = 1.33, an α=0.05 and power of 0.8 (Hypotheses: H0:θ ≦ 1.0 and Ha: θ ≧ 1.33)

Treatment schedule:

Group A：standard postoperative concurrent chemoradiotherapy.

Group B：Immediately after operation starts thalidomide (50) 4# per day and celecoxib (200) 2# bid for three weeks, in addition to standard postoperative concurrent chemoradiotherapy.

Group C：Immediately after operation starts cyclophosphamide (50) 1# per day and dexamethasone (0.5) 2# qd for three weeks, in addition to standard postoperative concurrent chemoradiotherapy.

Study Timeline

• Study Start: 2007-06
• Status Verified: 2009-07
• Study First Submitted: 2009-07-07
• Study First Submitted QC: 2009-07-07
• Study First Posted: 2009-07-08
• Primary Completion: 2012-12
• Study Completion: 2012-12
• Last Update Submitted: 2015-02-23
• Last Update Posted: 2015-02-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. Histologically proved oral cavity squamous cell carcinoma (buccal and mobile tongue).
2. Clinical stage T4a with skin involvement or resectable N2-3 by UICC/AJCC 1997 staging system.(24)
3. Curative-intent operation feasible and arranged.
4. Eastern Cooperative Oncology Group performance status ≦ 1.
5. A leukocyte count ≧3750/μL, Hb ≧10 g/dL, and a platelet count ≧100,000/μL.
6. A serum bilirubin level < 1.5 UNL (upper normal limit), serum creatinine level < 1.5 UNL or creatinine clearance > 60 mL/min.
7. Age less than 70 years old
8. Informed consent signed.

Exclusion Criteria

1. Evidence of distant metastatic.
2. Presence of another malignancy other than treated squamous/basal cell carcinoma of the skin.
3. Presence of uncontrolled hypertension, poorly controlled heart failure.
4. Presence of active infection.
5. Patients who have been or are being treated with chemotherapy, radiotherapy, immunotherapy, or other experimental therapies.
6. Women who test positive for pregnancy. Note: Patients received neck lymph node biopsy will be eligible and the stage will be given according to the preoperative status.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cyclophosphamide, Dexamethasone	Cyclophosphamide, Dexamethasone	Adjuvant anti-angiogenesis therapy
Thalidomide, Celebrex	Thalidomide, Celebrex	Adjuvant anti-angiogenesis therapy

Primary Outcome Measures

Name	Time	Method
The primary endpoint is the tumor-free survival that is defined as the duration between the dates of operation and the date of disease recurrence.	7 years

Secondary Outcome Measures

Name	Time	Method
Physical examinations, lab abnormality and other toxicities graded by the NCI Common Toxicity Criteria will be examined to evaluate safety profiles of the study treatments.	7 years