AF CRT +/- Nimorazole in HNSCC

NCT01880359 | Unknown Phase 3 DMC

• 2 other identifiers: EORTC-12192013-002441-12
• Study Type: interventional
• Target: 640
• Locations: 7 countries
• Sites: 19

Brief Summary

The drug nimorazole belongs to a class of chemicals known as 5-nitroimidazoles. Drugs from this class are used against infection. In addition, nimorazole makes tumor cells more sensitive to radiotherapy. Therefore, the investigators want to find out whether the addition of nimorazole to the standard treatment with radiotherapy in combination with chemotherapy with cisplatin shows activity against your type of head and neck cancer and is safe. Furthermore the investigators will investigate if a specific examination done with your tumor tissue will help to predict whether the treatment will work or not. To find out if the activity observed with this treatment is not caused by chance alone, the investigators need to obtain data from patients who receive this treatment and from patients who receive other treatments. The data from these two groups of patients will be compared to see which treatment is better. Participants will be split into 2 groups. Each group will receive different treatments. The treatment each group receives is determined by chance using a computer program. This works like flipping a coin and is called randomization. This helps to make sure that groups of patients are similar when the study starts. Neither you, your study doctor, nor the study staff can influence in which group you will be placed or which treatment you will receive. If allocated to group 1, Patient will receive radiotherapy in combination with chemotherapy with cisplatin and nimorazole as a pill. This is considered the 'experimental' treatment. If allocated to group 2, patient will receive radiotherapy in combination with chemotherapy with cisplatin and a so called 'placebo' as a pill. The placebo is a dummy treatment. It looks like the real one, but it is not. It contains no active ingredient/medicine.

Conditions

Locally Advanced Head and Neck HPV Negative Squamous Cell Cancers

Outcome Measures

Primary Outcomes (1)

• locoregional control rate

  9 years after first patient in

Secondary Outcomes (5)

• Time to distant metastasis

  9 years after first patient in

• Time to second cancer

  9 years after first patient in

• Overall survival

  9 years after first patient in

• Disease-specific free survival

  9 years after first patient in

• Acute and late morbidity

  9 years after first patient in

Study Arms (2)

Radiotherapy+ Cisplatin+ Placebo

PLACEBO COMPARATOR

Accelerated radiotherapy (Therapeutic Planning Target Volume (PTV): 70 Gray (Gy), 6 fractions/week, 35 fractions of 2 Gy, prophylactic PTV: 54.25 Gy, 6 fractions/week, 35 fractions of 1.55 Gy) + concomitant cisplatin (weekly schedule of 40mg/m2 (delivered on day 1, 8, 15, 22, 29) Patients will receive placebo (1.2 g/m2) 90 min (+/- 30 min) prior to each radiotherapy fraction but no more than 5 times a week (If the 6th radiotherapy fraction in a week is given on a separate day from the 5th fraction of radiotherapy, no nimorazole/placebo dose is received that day. If the 6th fraction of radiotherapy is given on the same day as the 5th fraction, nimorazole/placebo is given 90 minutes before the 5th radiotherapy fraction, only).

Drug: Cisplatin; Radiation: Radiotherapy; Drug: Placebo

Radiotherapy+ Cisplatin+ Nimorazole

EXPERIMENTAL

Accelerated radiotherapy (Therapeutic PTV: 70 Gy, 6 fractions/week, 35 fractions of 2 Gy, prophylactic PTV: 54.25 Gy, 6 fractions/week, 35 fractions of 1.55 Gy) + concomitant cisplatin (weekly schedule of 40mg/m2 (delivered on day 1, 8, 15, 22, 29) . Patients will receive nimorazole (1.2 g/m2) 90 min (+/- 30 min) prior to each radiotherapy fraction but no more than 5 times a week (If the 6th radiotherapy fraction in a week is given on a separate day from the 5th fraction of radiotherapy, no nimorazole/placebo dose is received that day. If the 6th fraction of radiotherapy is given on the same day as the 5th fraction, nimorazole/placebo is given 90 minutes before the 5th radiotherapy fraction, only).

Drug: Cisplatin; Radiation: Radiotherapy; Drug: Nimorazole

Interventions

Cisplatin DRUG

Radiotherapy+ Cisplatin+ Nimorazole; Radiotherapy+ Cisplatin+ Placebo

Radiotherapy RADIATION

Radiotherapy+ Cisplatin+ Nimorazole; Radiotherapy+ Cisplatin+ Placebo

Placebo DRUG

Radiotherapy+ Cisplatin+ Placebo

Nimorazole DRUG

Radiotherapy+ Cisplatin+ Nimorazole

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed tumors classified as stage III-IV located in the larynx, oropharynx and hypopharynx (unknown primary should be excluded; oral cavity are not eligible)
• Human papillomavirus(HPV)/p16 negative (≤70% positively stained cells), assessed locally for tumors of the oropharynx
• Tumors of the larynx and hypopharynx regardless of the HPV status
• Histopathological diagnosis of invasive squamous cell carcinoma in the primary tumor
• World Health Organization (WHO) performance 0-2
• All Hematology and biochemical investigations, should be done within 4 weeks before randomization (maximum 6 weeks before treatment starts)
• Normal bone marrow function based on routine blood samples, i.e. neutrophils ≥ 1.0 x 109/L, platelets ≥ 75 x 109/L, hemoglobin ≥ 10.0 g/dL or 6.2 mmol/L
• Normal kidney function creatinine clearance ≥ 60ml/min, and Electrolyte balance: calcium ≤ 11.5 mg/dl or 2.9 mmol/l, magnesium ≥ 1.2 mg/dl or 0.5 mmol/l
• Normal liver function assessed by routine laboratory examinations, i.e. bilirubin \< 1.5 x Upper Limit of Normal (ULN), Aspartate aminotransferase (AST)\< 3 x ULN, alkaline phosphatases \< 3 x ULN
• No prior or current anticancer treatment to the head and neck area (e.g. radical attempted or tumor reductive surgery, neo-adjuvant chemotherapy, Epidermal Growth Factor Receptor (EGFR) inhibitors or radiotherapy).
• Patients must be candidate for curative intent external beam chemo-radiotherapy, and must be expected to complete the treatment.
• All patients should have an oral and dental examination including preferably clinical and radiological examination. Whenever indicated, extraction of dental elements should be carried out at least 10 days before treatment start;for 1-2 (max 2) monoradicular single tooth extractions (if not continous a max of 4) without bone resection 5 days (as a minimum) are allowed.
• Radiotherapy planned to start within acceptable delay (preferably within 2 weeks and a maximum of 4 weeks from randomization).
• Radiotherapy planned to start within 8 weeks from baseline imaging tumor assessment.
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial

You may not qualify if:

• Patients who have received treatment with any investigational drug substance within 4 weeks prior to randomization;
• Current participation in any other interventional clinical study;
• Pregnant or breast-feeding female patient. Pregnancy test should be done within 72 hours from treatment start;
• Female subjects of childbearing potential (defined as a sexually mature woman who 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally post-menopausal (amenorrhoea following cancer therapy does not rule out childbearing potential) for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months)) not willing to use adequate contraception during study and for 6 month after last dose of study drug;
• Male subjects not willing to use condoms throughout study drug therapy, and for 6 months after cessation of study therapy if their partner is of childbearing potential and has no contraception;
• Known or suspected HIV infection;
• Second malignancies in the 3 years prior to study entry with the exception of surgically cured carcinoma in situ of the cervix, in situ breast cancer, incidental finding of stage T1a or T1b prostate cancer, and basal/squamous cell carcinoma of the skin;
• Uncontrolled or chronic bacterial, fungal or viral infection;
• Known or suspected hypersensitivity to component(s) of investigational product or cisplatin contraindication;
• All indicated timelines and absolute values requested by the eligibility criteria must be adhered to. However, a maximum of +/- 10% of the reference value for laboratory parameters and a maximum of +/- 3 days for timelines may be acceptable. Discussion with EORTC Headquarters and study coordinator is encouraged.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Danish Head and Neck Cancer Group: collaborator

Study Sites (19)

Royal Brisbane And Women's Hospital

Brisbane, QLD 4029, Australia

Location

Princess Alexandra Hospital - University Of Queensland

Brisbane, QLD 4102, Australia

Location

Royal North Shore Hospital

St Leonards, NSW 2065, Australia

Location

Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet

Brussels, 1000, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

U.Z. Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Centre Georges-Francois-Leclerc

Dijon, 21079, France

Location

CHU de Tours - Hopital Bretonneau

Tours, 37044, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum

Berlin, Germany

Location

Ludwig-Maximilians-Universitaet Muenchen - Klinikum der Universitaet Muenchen - Campus Grosshadern

München, 81377, Germany

Location

Vrije Universiteit Medisch Centrum

Amsterdam, 7007MB, Netherlands

Location

Radboud University Medical Center Nijmegen

Nijmegen, 6500 H, Netherlands

Location

Medical University Of Gdansk

Gdansk, 80 211, Poland

Location

The Great Poland Cancer Centre

Poznan, Poland

Location

Maria Sklodowska-Curie Memorial Cancer Centre

Warsaw, Poland

Location

Lower Silesian Oncology Centre

Wroclaw, Poland

Location

Hôpitaux universitaires de Genève - HUG - site de Cluse-Roseraie

Geneva, 1211, Switzerland

Location

UniversitaetsSpital Zurich

Zurich, 8091, Switzerland

Location

MeSH Terms

Interventions

Cisplatin; Radiotherapy; Nimorazole

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics; Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jens Overgaard

  Aarhus University Hospital

  STUDY CHAIR

• Vincent Grégoire

  Cliniques Universitaires St. Luc

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2013
• First Posted: June 19, 2013
• Study Start: July 25, 2014
• Primary Completion: September 6, 2019
• Study Completion: January 9, 2023
• Last Updated: May 10, 2022

Record last verified: 2022-05

Locations

BE (3); FR (3); DE (2); NL (2); PL (4); CH (2); AU (3)