IAEA-HypoX. Accelerated Radiotherapy With or Without Nimorazole in Squamous Cell Carcinoma of the Head and Neck (IAEA-HypoX)

IAEA-HypoX. A Randomized Multicenter Study of Accelerated Fractionated Radiotherapy With or Without the Hypoxic Radiosensitizer Nimorazole in the Treatment of Squamous Cell Carcinoma of the Head and Neck

The purpose of this study is to test the hypothesis that radiotherapy of head and neck carcinoma can be improved by hypoxic modification of radiotherapy using nimorazole as a hypoxic radiosensitizer in association with accelerated fractionation, in an unselected patient population in a global environment.

Study Overview

• Status: Terminated
• Conditions: Head and Neck Carcinoma
• Intervention / Treatment: Radiation: Accl. RT; Radiation: Accl. radiotherapy + Nimorazole

Detailed Description

Squamous cell carcinoma in the head & neck region (HNSCC) accounts for approximately 7% of all cancers worldwide & around 75% of all HNSCC cases are seen in the less developed countries.

Significant improvement in loco-regional control & disease specific survival by radiation therapy could be achieved by reducing the overall treatment time by "Accelerated Fractionation" schedule.

Modification of hypoxia by Nimorazole demonstrated significant improved local effect of radiation with neither serious nor lasting side effects. So, it is expected that the optimal treatment option is reducing the overall treatment time with concomitant use of Nimorazole. Such treatment principle is optimal for testing in developing countries.

The aim of the study:

• To determine the possible therapeutic gain of using nimorazole given as a hypoxic radiosensitizer in conjunction with accelerated fractionated radiotherapy of invasive squamous cell carcinoma of the larynx, pharynx and oral cavity, and
• To determine whether the addition of Nimorazole to primary curative radiotherapy is feasible and tolerable on a worldwide scale.
• To evaluate the tolerance, compliance and toxicity of using nimorazole.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Radiation Oncology Department, National Cancer Institute
• Estonia
  • Tallin, Estonia, 13419
    • Radiation Oncology Center
• Pakistan
  • Islamabad, Pakistan
    • Nuclear Medicine, Oncology & Radiotherapy Institute, Radiation Oncology Department G-8/3
  • Karachi, Pakistan
    • Karachi Institute of Radiotherapy and Nuclear Medicine
  • Peshawar, Pakistan
    • Institute of Radiotherapy and Nuclear Medicine (IRNUM) Hospital Peshawar
• Slovenia
  • Ljubljana, Slovenia
    • Institute of Oncology Department of Radiation Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Tumor classified as stage I-IV located in oropharynx, hypopharynx, larynx (not glottic stage I-II), or oral cavity according to the TNM classification.
• Histopathological diagnosis of invasive squamous cell carcinoma in the primary tumor.
• Informed consent according to the Helsinki declaration and local regula-tions.
• The patient must be candidate for external beam radical radiotherapy, and must be expected to accomplish the treatment.
• Performance status 0-2 according to WHO criteria.
• The patient should not have symptoms of peripheral neuropathy assessed by clinical examination.
• Normal function of liver and kidney by routine laboratory examinations. The patient must not be pregnant

Exclusion Criteria:

• Distant metastases.
• The patient should not be in a state or condition 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.
• Surgical excision (except biopsy), prior or planned (including elective neck dissection).
• The existence of synchronous multiple malignancies (not leukoplakia).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Accl. RT; Accelerated Radiotherapy 66-70 Gy, 2Gy/fx, 6fx/week	Radiation: Accl. RT; Accelerated Radiotherapy: Radiotherapy 66-70 Gy, 2Gy/fx, 6fx/week; Other Names: Radiation Oncology, Accelerated fractionation
EXPERIMENTAL: Accl. RT + Nimorazole; Accelerated Radiotherapy 66-70 Gy, 2Gy/fx, 6fx/week + Nimorazole	Radiation: Accl. RT; Accelerated Radiotherapy: Radiotherapy 66-70 Gy, 2Gy/fx, 6fx/week; Other Names: Radiation Oncology, Accelerated fractionation; Radiation: Accl. radiotherapy + Nimorazole; Radiation: Radiotherapy 66-70 Gy, 2Gy/fx, 6fx/week plus Nimorazole (tablets or powder) 1.2 g/m2 body surface in connection with the first daily radiation treatments; Other Names: Hypoxic radiosensitizer, Nimorazole, Nimoral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Locoregional control after curative intended radiotherapy +/- Nimorazole	5-years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		5-years
Disease specific survival		5.years
Treatment related morbidity	Treatment related acute and late morbidity releted to radiotherapy and/or nimorazole treatment	5-years

Collaborators and Investigators

• Sponsor: Danish Head and Neck Cancer Group
• Collaborators: International Atomic Energy Agency; Danish Center for Interventional Research in Radiation Oncology (CIRRO)
• Investigators: Principal Investigator: Jens Overgaard, MD, Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark; Study Director: Mohamed Hassan, MD, study coordinator

Publications and helpful links

Helpful Links

• Trial homepage

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): May 1, 2016

Study Registration Dates

• First Submitted: August 14, 2011
• First Submitted That Met QC Criteria: January 10, 2012
• First Posted (ESTIMATE): January 11, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): November 25, 2016
• Last Update Submitted That Met QC Criteria: November 22, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Accelerated radiotherapy; Head and neck carcinoma; Hypoxic modification with Nimorazole
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antitrichomonal Agents; Nimorazole
• Other Study ID Numbers: IAEA-HypoX (OTHER_GRANT: IAEA, CIRRO; Aarhus University, Denmark, AZANTA Denmark)