Locally Advanced Head and Neck HPV Negative Squamous Cell CancersPhase 3NCT01880359
AF CRT +/- Nimorazole in HNSCC
A Phase 3 study testing Cisplatin, Radiotherapy and Nimorazole in people with Locally Advanced Head and Neck HPV Negative Squamous Cell Cancers, run by European Organisation for Research and Treatment of Cancer - EORTC at 19 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Head and Neck HPV Negative Squamous Cell Cancers
- What is being tested?
- Cisplatin, Radiotherapy and Nimorazole
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 640 participants
- Where
- 19 sitesin 7 countries
- Study dates
- 25 Jul 2014to 9 Jan 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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)
Who cannot join
- 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;
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- 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.
Trial locations and contacts
19 sites in 7 countries.
19 sites in 7 countries
Poland4 sites
Medical University Of Gdansk
Gdansk, 80 211
The Great Poland Cancer Centre
Poznan
Maria Sklodowska-Curie Memorial Cancer Centre
Warsaw
Lower Silesian Oncology Centre
Wroclaw
Australia3 sites
Royal Brisbane And Women's Hospital
Brisbane, QLD 4029
Princess Alexandra Hospital - University Of Queensland
Brisbane, QLD 4102
Royal North Shore Hospital
St Leonards, NSW 2065
Belgium3 sites
Hopitaux Universitaires Bordet-Erasme - Institut Jules Bordet
Brussels, 1000
Cliniques Universitaires Saint-Luc
Brussels, 1200
U.Z. Leuven - Campus Gasthuisberg
Leuven, 3000
France3 sites
Centre Georges-Francois-Leclerc
Dijon, 21079
CHU de Tours - Hopital Bretonneau
Tours, 37044
Institut Gustave Roussy
Villejuif, 94805
Germany2 sites
Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum
Berlin
Ludwig-Maximilians-Universitaet Muenchen - Klinikum der Universitaet Muenchen - Campus Grosshadern
München, 81377
Netherlands2 sites
Vrije Universiteit Medisch Centrum
Amsterdam, 7007MB
Radboud University Medical Center Nijmegen
Nijmegen, 6500 H
Switzerland2 sites
Hôpitaux universitaires de Genève - HUG - site de Cluse-Roseraie
Geneva, 1211
UniversitaetsSpital Zurich
Zurich, 8091
About this study
Official 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.
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.
Read more
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.
- Being tested
- Cisplatin, Radiotherapy, Placebo, Nimorazole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CisplatinDrug
RadiotherapyRadiation
PlaceboDrug
NimorazoleDrug
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Drug: Cisplatin; Radiation: Radiotherapy; Drug: Nimorazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
locoregional control rate
Measured: 9 years after first patient in
Secondary outcomes (5)
Time to distant metastasis
Measured: 9 years after first patient in
Time to second cancer
Measured: 9 years after first patient in
Overall survival
Measured: 9 years after first patient in
Disease-specific free survival
Measured: 9 years after first patient in
Acute and late morbidity
Measured: 9 years after first patient in
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2013 (estimated)
- Study start25 Jul 2014
- Primary completion6 Sep 2019
- Study completion9 Jan 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Head and Neck HPV Negative Squamous Cell CancersStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 640 participants (estimated)
Sponsor and investigators
- Sponsor type
- Research network
- Collaborators
- Danish Head and Neck Cancer Group
- Responsible party
- Sponsor
- Investigators
- Jens Overgaard, Study chair, Aarhus University HospitalVincent Grégoire, Study chair, Cliniques Universitaires St. Luc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01880359
- Sponsor's protocol ID
- EORTC-1219
- Other IDs
- 2013-002441-12
- Status last verified
- May 2022
- First submitted
- 12 Jun 2013
- Last updated
- 10 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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.
- ClinicalTrials.gov ID
- NCT01880359
- Acronym / sponsor ID
- EORTC-1219
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 640 participants (estimated)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Collaborators
- Danish Head and Neck Cancer Group
- Study start
- 25 Jul 2014 (actual)
- Primary completion
- 6 Sep 2019 (actual)
- Study completion
- 9 Jan 2023 (estimated)
- First posted
- 19 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Radiotherapy+ Cisplatin+ Placebo | Placebo comparator | Drug: Cisplatin, Radiation: Radiotherapy, Drug: PlaceboAccelerated 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). |
| Radiotherapy+ Cisplatin+ Nimorazole | Experimental | Drug: Cisplatin, Radiation: Radiotherapy, Drug: NimorazoleAccelerated 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 |
Primary outcome
locoregional control rate
Time frame: 9 years after first patient in
5 secondary outcomes
Time to distant metastasis
Time frame: 9 years after first patient in
Time to second cancer
Time frame: 9 years after first patient in
Overall survival
Time frame: 9 years after first patient in
Disease-specific free survival
Time frame: 9 years after first patient in
Acute and late morbidity
Time frame: 9 years after first patient in
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jens Overgaard study chair
Aarhus University Hospital
Vincent Grégoire study chair
Cliniques Universitaires St. Luc
19 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cisplatin, Radiotherapy and Nimorazole in people with Locally Advanced Head and Neck HPV Negative Squamous Cell Cancers, run by European Organisation for Research and Treatment of Cancer - EORTC at 19 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Poland, Australia, Belgium, France, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
locoregional control rate (time frame: 9 years after first patient in). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2022.