A prospective study of therapeutic outcome in patients with locally advanced Head and Neck Cancers treated with chemo-radiation in combination with Nimorazole

Phase 2

Recruiting

Conditions: Locally Advanced Oro-pharyngeal, Laryngeal and Hypopharyngeal cancer patients eligible for concurrent chemo-radiation

Brief Summary: The purpose of the present study is to improve the effect of radiotherapy given to patients with locally advanced head and neck carcinoma, who are candidates for primary chemo-radiation therapy alone. This rationale has been recently tested in a Phase II (DAHANCA-18 study) setting with good results. The protocol seeks to test the hypothesis that radiotherapy of head and neck carcinoma can be improved by hypoxic modification of tumours using nimorazole as a hypoxic radiosensitizer in conventional treatment strategies. The study will evaluate the loco-regional tumour control after chemo-radio-therapy, acute toxicity, disease-free and overall survival, and the early and late treatment related morbidity. This will be correlated with a translational component, where the treatment outcome will be compared with specific tumour characteristics (HPV status and p53 status) as well as circulating hypoxia markers present in plasma.

Recruitment & Eligibility

Inclusion Criteria

1)Tumour classified as stage III-IV located in oropharynx, hypopharynx and larynx according to the TNM classification.
1. Histopathological diagnosis of invasive squamous cell carcinoma in the primary tumour.
1. Age > 18 years and < 75 years.
1. Informed consent according to the Helsinki declaration and institutional regulations.
1. The patient must be candidate for external beam radical radiotherapy, and must be expected to accomplish the treatment.
1. Performance status 0-2 according to WHO criteria.
1. The patient should not have symptoms of peripheral neuropathy assessed by clinical examination.
1. Normal function of liver and kidney by routine laboratory examinations.
1. The patient must not be pregnant.

Exclusion Criteria

1. Distant metastases.
1. The patient should not have any other co-morbidities or conditions that could be expected to influence the outcome of treatment, or complicate the assessment or the treatment follow-up, or (apart from the present disease) reduce the life expectancy.
1. Surgical excision (except biopsy), prior or planned (including elective neck dissection).
1. The existence of synchronous multiple malignancies (not leucoplakia).
1. Use of Vitamin K agonists (since 5-nitroimidazoles are inhibitors of CYP2C9).

Primary Outcome Measures

Name	Time	Method
To study Loco-regional Control of disease	5 years from completion of definitive treatment

Secondary Outcome Measures

Name	Time	Method
1) Overall Survival	2) Test Osteopontin as a marker for hypoxia to predict efficacy of Nimorazole.

Locations (1): Amrita Institute of Medical Sciences and Research
🇮🇳
Ernakulam, KERALA, India
Amrita Institute of Medical Sciences and Research
🇮🇳Ernakulam, KERALA, India
Dr Anoop R
Principal investigator
04842801234
anoopr@aims.amrita.edu