A Study of High-Risk Oral Cavity Cancer

Multicentre，A Phase II/III Randomized Study of Adjuvant Anti-Angiogenesis Therapy for Patients of High-Risk Oral Cavity Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Oral Cavity Cancer
• Intervention / Treatment: Drug: Thalidomide, Celebrex; Drug: Cyclophosphamide, Dexamethasone

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 Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Standard postoperative concurrent chemoradiotherapy
Experimental: Thalidomide, Celebrex; Adjuvant anti-angiogenesis therapy	Drug: Thalidomide, Celebrex; Immediately after operation starts thalidomide (50) 4# per day and celecoxib (Celebrex)(200) 2# bid for three weeks, in addition to standard postoperative concurrent chemoradiotherapy; Other Names: Adjuvant Therapy
Active Comparator: Cyclophosphamide, Dexamethasone; Adjuvant anti-angiogenesis therapy	Drug: Cyclophosphamide, Dexamethasone; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: National Health Research Institutes, Taiwan
• Collaborators: National Taiwan University Hospital; Mackay Memorial Hospital; Sun Yat-sen University; Chang Gung Memorial Hospital; Buddhist Tzu Chi General Hospital; National Cheng-Kung University Hospital; Changhua Christian Hospital; Kaohsiung Veterans General Hospital.; Chi Mei Medical Hospital
• Investigators: Principal Investigator: Ruey-Long Hong, MD, PhD., Department of Oncology, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: July 7, 2009
• First Submitted That Met QC Criteria: July 7, 2009
• First Posted (Estimate): July 8, 2009

Study Record Updates

• Last Update Posted (Estimate): February 25, 2015
• Last Update Submitted That Met QC Criteria: February 23, 2015
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: High-Risk Oral Cavity Cancer,; Anti-Angiogenesis
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Mouth Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Cyclooxygenase 2 Inhibitors; Dexamethasone; Cyclophosphamide; Thalidomide; Celecoxib
• Other Study ID Numbers: T1306

Drug and device information, study documents

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