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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01880359




Registration number
NCT01880359
Ethics application status
Date submitted
12/06/2013
Date registered
19/06/2013
Date last updated
10/05/2022

Titles & IDs
Public title
AF CRT +/- Nimorazole in HNSCC
Scientific title
A Blind Randomized Multicenter Study of Accelerated Fractionated Chemo-radiotherapy With or Without the Hypoxic Cell Radiosensitizer Nimorazole (Nimoral), Using a 15-gene Signature for Hypoxia in the Treatment of Squamous Cell Carcinoma of the Head and Neck.
Secondary ID [1] 0 0
2013-002441-12
Secondary ID [2] 0 0
EORTC-1219
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced Head and Neck HPV Negative Squamous Cell Cancers 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cisplatin
Treatment: Other - Radiotherapy
Treatment: Drugs - Placebo
Treatment: Drugs - Nimorazole

Placebo Comparator: Radiotherapy+ Cisplatin+ Placebo - 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).

Experimental: Radiotherapy+ Cisplatin+ Nimorazole - 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).


Treatment: Drugs: Cisplatin


Treatment: Other: Radiotherapy


Treatment: Drugs: Placebo


Treatment: Drugs: Nimorazole
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
locoregional control rate
Timepoint [1] 0 0
9 years after first patient in
Secondary outcome [1] 0 0
Time to distant metastasis
Timepoint [1] 0 0
9 years after first patient in
Secondary outcome [2] 0 0
Time to second cancer
Timepoint [2] 0 0
9 years after first patient in
Secondary outcome [3] 0 0
Overall survival
Timepoint [3] 0 0
9 years after first patient in
Secondary outcome [4] 0 0
Disease-specific free survival
Timepoint [4] 0 0
9 years after first patient in
Secondary outcome [5] 0 0
Acute and late morbidity
Timepoint [5] 0 0
9 years after first patient in

Eligibility
Key inclusion criteria
- 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

- All subjects must agree to abstain from donating blood while receiving therapy and for
four weeks following discontinuation of therapy.

- All subjects must agree not to share study medication with another person and to
return all unused study drug to the investigator.

- Before patient registration, written informed consent must be given according to
International Conference on Harmonisation /Good Clinical Practice (ICH/GCP), and
national/local regulations (including material acquisition for central testing of the
hypoxic signature)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/07/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
9/01/2023
Actual
Sample size
Target
640
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Brisbane And Women's Hospital - Brisbane
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - University Of Queensland - Brisbane
Recruitment hospital [3] 0 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 0 0
QLD 4029 - Brisbane
Recruitment postcode(s) [2] 0 0
QLD 4102 - Brisbane
Recruitment postcode(s) [3] 0 0
NSW 2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Brussels
Country [2] 0 0
Belgium
State/province [2] 0 0
Leuven
Country [3] 0 0
France
State/province [3] 0 0
Dijon
Country [4] 0 0
France
State/province [4] 0 0
Tours
Country [5] 0 0
France
State/province [5] 0 0
Villejuif
Country [6] 0 0
Germany
State/province [6] 0 0
Berlin
Country [7] 0 0
Germany
State/province [7] 0 0
Muenchen
Country [8] 0 0
Netherlands
State/province [8] 0 0
Amsterdam
Country [9] 0 0
Netherlands
State/province [9] 0 0
Nijmegen
Country [10] 0 0
Poland
State/province [10] 0 0
Gdansk
Country [11] 0 0
Poland
State/province [11] 0 0
Poznan
Country [12] 0 0
Poland
State/province [12] 0 0
Warsaw
Country [13] 0 0
Poland
State/province [13] 0 0
Wroclaw
Country [14] 0 0
Switzerland
State/province [14] 0 0
Geneva
Country [15] 0 0
Switzerland
State/province [15] 0 0
Zurich

Funding & Sponsors
Primary sponsor type
Other
Name
European Organisation for Research and Treatment of Cancer - EORTC
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Danish Head and Neck Cancer Group
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01880359
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jens Overgaard
Address 0 0
Aarhus University Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01880359