Clinical Trial Result Information

Protocol number
ML16542

Title of Study
A dose-finding study of capecitabine (Ro 09-1978) in combination with standard radiotherapy in head and neck cancer patients

Sponsor
Roche S.p.A.

Company division
Pharmaceutical

Product name
Xeloda

Generic name
capecitabine

Therapeutic area
Head and Neck Cancer

Clinical study summary
This was a prospective, open-label, non-randomized, single-center, Phase II study in patients with head and neck cancer to determine the maximum tolerated dose and to evaluate the safety and efficacy of oral capecitabine (Xeloda) in combination with radiotherapy. NB This study was prematurely terminated

Study center(s)
1

Phase of development
II

Objectives
Primary: To determine the maximum tolerated dose, the dose-limiting toxicity (DLT), and the recommended dose of Xeloda in combination with radiotherapy in patients with head and neck cancer. Secondary: (1) To evaluate the safety of a regimen with standard doses of radiotherapy in combination with escalating doses of Xeloda; and (2) To evaluate the anti-tumor activity of the combination of radio-chemotherapy in terms of response rate, duration of response, and time to disease progression.

Methodology
After screening, eligible patients were to receive escalating doses of oral Xeloda, 350-825mg/m2/day, in two daily divided doses, for approximately 7 weeks, from first to last day of radiotherapy. Dose-limiting toxicity was recorded, and tumor assessments made, during and after treatment.

Number of patients (planned/analyzed)
2

Diagnosis and main criteria for inclusion
Patients with histologically or cytologically confirmed head and neck carcinoma who were candidates for definitive or salvage radiotherapy and were judged to benefit from combined chemo-radiotherapy; primary site at the oropharynx, hypopharynx, larynx, or oral cavity; 18–80 years of age, inclusive; no prior radiotherapy for head and neck cancer.

Test product, dose and mode of administration or test procedure
Oral Xeloda 350–825 mg/m2 bid.

Duration of treatment
Approximately 7 weeks (from beginning to end of radiotherapy)

Criteria for evaluation (efficacy, safety)
Dose limiting toxicity; tumor assessment

Statistical methods
Not applicable

Summary (efficacy, safety, other results)
The study was discontinued after the inclusion of 2 patients, due to newly available data supporting the use of more aggressive therapy, based on radiotherapy and 5-fluorouracil/cisplatin/paclitaxel combination chemotherapy, in the selected patient population.

Patient No. 1 received Xeloda 500 mg bid for 7 weeks (with treatment interrupted for 1 day due to stomatitis) and radiotherapy (total dose 70 Gy, 2 Gy per fraction). Anemia and lymphocytopenia were observed at baseline and throughout the study. Stomatitis and asthenia, as well as creatinine increase, newly emerged during the study. On the whole, no DLT was identified. Following completion of study medication, treatment-related cutaneous toxicity and non-treatment–related cardiac ischemia occurred, the latter reported as a serious event. At the post-treatment efficacy assessment, spiral computed tomography (CT) scan showed complete response in hypopharynx and regional lymph node lesions. However, follow-up assessment showed a new lesion at liver spiral CT scan, with progression leading to death.

Patient No. 2 withdrew from the study because of an acute myocardial infarction before starting treatment with study medication.

Safety and tolerability assessments in the two patients did not reveal unexpected toxicities of clinical importance.

Conclusions
No conclusions can be drawn from the study.

Date of report
7/26/2004