Phase I/II study of combined treatment with AT-101, cisplatin and radiotherapy in patients with locally advanced head and neck cancer

Conditions: head and neck squamous cell carcinoma
head and neck cancer
10027655

Registration Number: NL-OMON33661

Lead Sponsor: Antoni van Leeuwenhoek Ziekenhuis

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 50

Inclusion Criteria

• Histologically proven squamous cell carcinoma of the head and neck
• Oral cavity, oropharyngeal, or hypopharyngeal carcinoma
• Inoperable TNM stage III/IV, M0
• Patient must have measurable disease
• Age > 18 years
• Performance status WHO 0-2
• No prior r adiation therapy to head and neck region
• No prior cisplatin-based chemotherapy
• Adequate laboratory results:
- WBC > 4.0 x 10E9/l
- platelets > 100 x 10E9/l
- calculated or 24 hour creatinine clearance > 50 ml/min
- ASAT/ALAT < 2.5 times upper limit of normal range
- Bilirubin < 1.5 x upper limit of institution's normal range
• Willingness to use contraception by a method that is deemed effective by the Investigator throughout the treatment period and for at least 30 days following the last dose of therapy
• Willing and able to undergo blood sampling for pharmacokinetics
• Signed written informed consent before entry into study.
• Entry criteria for translational research:
- Willing and able to undergo blood sampling, harvesting of buccal smears and tumor biopsy (mandatory)
- Willing and able to undergo skin biopsy and nuclear scanning (optional)

Exclusion Criteria

• Breast feeding or pregnancy
• Uncontrolled arrhythmia
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, ulcerative colitis, inflammatory bowel disease, or partial or complete small bowel obstruction
• Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification.
• Known active symptomatic fungal, bacterial and/or viral infection including active HIV
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoint:<br /><br><br /><br>• Tolerability of combined treatment consisting of oral AT-101 and concurrent<br /><br>cisplatin-based chemoradiation, i.e. the definition of a feasible, safely<br /><br>administrable daily dose of oral AT-101, close to the MTD, in combination with<br /><br>standard chemoradiation.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints:<br /><br><br /><br>• Identification of the Dose-Limiting Toxicity (DLT)<br /><br>• Incidence, intensity and reversibility of observed adverse events/reactions<br /><br>of AT-101 in combination with cisplatin-radiotherapy<br /><br>• Study on translational research parameters:<br /><br>- Determination of systemic and local (intratumoral/normal tissue)<br /><br>accumulation of cisplatin-DNA adduct formation, in white blood cells (WBC),<br /><br>buccal cells and primary tumor (if accessible)<br /><br>- Immunohistochemical assessment of proteins involved in apoptotic response,<br /><br>by analysis of baseline tumor and normal skin biopsies and repeated<br /><br>on-treatment biopsies.<br /><br>- In vivo detection of apoptosis, using 99mTc-Annexin V scintigrapghy, at<br /><br>baseline and during treatment<br /><br>• Pharmacokinetics of AT-101<br /><br>• Document anti-tumor effects of combined modality treatment, according to<br /><br>RECIST criteria</p><br>