Head and Neck NeoplasmsPhase 2CTXMAB+RTNCT01216020
Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer
A Phase 2 study testing cetuximab and cisplatin (associated to radiotherapy) in people with Head and Neck Neoplasms and Laryngeal Neoplasms, run by Azienda USL 4 Prato at 7 sites in Italy.
Trial summary
BACKGROUND: Concomitant radiotherapy and cisplatin (CDDP) based chemotherapy is the standard treatment for LA-NHSCC. This combined modality treatment is linked with considerable acute local and systemic toxicity.EGFR is overexpressed in 90-100% of the HNSCC cases and is considered an unfavourable prognostic marker. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Neoplasms, Laryngeal Neoplasms, Mouth Neoplasms
- What is being tested?
- cetuximab and cisplatin (associated to radiotherapy)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 7 sitesItaly
- Study dates
- Oct 2010to 20 May 2015
- Phase
- Phase 2
- 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
- Histologically confirmed squamous cell carcinoma (with biopsy on the primary and / or lymph node metastases) of the oral cavity, oropharynx, hypopharynx, larynx supraglottix;
- Locally advanced disease, defined by one of the following criteria: any T, N +, M0 (excluding T1, N1), T3-4, N0, M0;
- Not cancer nasopharynx or paranasal sinuses or salivary glands;
- General conditions and associated diseases which does not allow to perform chemotherapy or radiotherapy in a radical view;
- No other surgical treatments, chemotherapy or radiotherapy for cancer of head and neck or elsewhere, except non-melanoma skin cancer or in situ cervical cancer and other solid tumors for which radical treatment has been completed > three years prior to enrollment in the study and for which the patient has remained continuously free of disease;
- Accessibility to follow-up;
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- Signing of informed consent;
- Interval between examinations of local staging and randomization, maximum 3 weeks
- Interval between randomization and initiation of treatment, maximum 2 weeks
Who cannot join
- Age <18 years
- ECOG performance status > 0-1
- Hemoglobin <9 g / dL
- Counts of granulocytes, total <1.5 x 10 ^ 9 / L
- Platelet count <100 x 10 ^ 9 / L
- Bilirubin> 1.5 times upper limit of normal (ULN)
Show all 23Show fewer
- AST or ALT> 3 times ULN
- Creatinine clearance > 50 mL/min
- Mg > 0.5 mmol/L
- Pregnancy or lactation
- Presence of allergy to study drug or to the excipients used in their formulation
- Peripheral neuropathy ≥ grade 2 (CTCAE v3.0)
- Hearing loss / tinnitus ≥ grade 3 (CTCAE v3.0)
- One of the following conditions:
- Myocardial infarction within 12 months prior to randomization
- Severe congestive heart failure
- Unstable angina
- Cardiomyopathy in act
- Ventricular arrhythmia
- uncontrolled hypertension
- Severe psychotic disorders in act
- Severe infection in act
- Any other serious illness that could interfere with the administration of the therapy provided by the protocol
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Italy7 sites
Radiotherapy Dept., Arezzo Hospital
Arezzo
Radiotherapy Dept., Brescia University and Medical Oncology Dept., Brescia Hospital
Brescia, 25100
Radiotherapy Dept., Florence University
Florence, 50100
Radiotherapy Dept., Genoa University
Genoa
Radiotherapy Dept., Azienda USL 4 Prato
Prato, 59100
Radiotherapy Dept., Siena University
Siena
Radiotherapy Dept., Turin University
Torino
About this study
Official title: Multiinstitutional Open Label Randomized Phase II Study Comparing Cetuximab and Radiotherapy Versus Cisplatin and Radiotherapy as Firstline Treatment for Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LA-NHSCC)
BACKGROUND:
Concomitant radiotherapy and cisplatin (CDDP) based chemotherapy is the standard treatment for LA-NHSCC. This combined modality treatment is linked with considerable acute local and systemic toxicity.EGFR is overexpressed in 90-100% of the HNSCC cases and is considered an unfavourable prognostic marker. EGFR costitutive activation is linked with HNSCC pathogenesis.
Read more
Cetuximab is a monoclonal anti-EGFR antibody blocking the activation of the receptor and signal transduction. Cetuximab combined with radiotherapy is superior to radiotherapy only in the treatment of LA-HNSCC and is characterized by an acceptable toxicity profile.
RATIONALE:
A direct comparison between concomitant chemoradiotherapy with Cisplatin and the concomitant treatment with radiotherapy associated to cetuximab does not exist.
STUDY DESIGN:
Arm A: Radical radiotherapy (doses and volumes) concomitant with chemotherapy with Cisplatin (40 mg/mq/week) Arm B: Radical radiotherapy (doses and volumes) concomitant with therapy with the monoclonal antibody Cetuximab (400 mg/m2 ["loading dose"] and subsequently 250 mg /m2/week)
Read the detailed description
PRIMARY OBJECTIVES:
Evaluation and comparison of the compliance of the two treatments;
SECONDARY OBJECTIVES:
Evaluation and comparison of the grade and incidence of acute toxicity; Evaluation and comparison of local control; Evaluation and comparison of event free survival (both local control and distant metastases); Evaluation and comparison of cause specific and overall survival.
INCLUSION/EXCLUSION CRITERIA
- Histologically confirmed squamous cell carcinoma (biopsy obtained from the tumor and/or from its lymphnodal metastases) originating from oral cavity, oropharynx, hypopharinx, supraglottic larynx;
- Locally advanced disease, defined by one of the following criteria: every T, N+, M0 ( T1, N1 cases excluded); T3-4, N0, M0;
- Not a nasopharynx, paranasal sinuses, salivary glands tumor;
- General conditions and concomitant diseases not considered a contraindication for chemotherapy or curative radiotherapy;
- No other surgical, chemotherapeutic or radiotherapic treatments for ENT region tumors or for tumors of other anatomical sites (with the exception of non-melanoma cutaneous tumors and of the carcinoma in situ of the uterine cervix and of other solid tumors whose primary treatment has been completed more than 3 years before the accrual in this study and never relapsed since primary treatment (the patient having been since then continuously disease- free);
- Availability for follow-up;
- Signed informed consent;
- An interval of maximum 3 weeks between staging procedures for local disease and randomization
- An interval of maximum 2 weeks between randomization and the onset of the treatment
- Being tested
- cetuximab, cisplatin (associated to radiotherapy)
- Keywords
- Head and Neck Cancer, Radiotherapy, Cetuximab, Cisplatin
- Medical subject headings
- Head and Neck Neoplasms, Laryngeal Neoplasms, Mouth Neoplasms, Pharyngeal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cetuximabDrug
Also called Erbitux
- Cetuximab is given according to the standard mode of administration: "loading dose" : 400 mg/m2 one week before the start of radiotherapy (week -1), followed by a weekly dose of 250 mg/m2 during the weeks of the treatment with radiotherapy.
- Radiotherapy: Doses: Clinical sites of disease (T e N) : total dose of 70 Gy given with a fractional dose of 2 Gy/day; "prophylactic" nodal volume (N) : total dose of 50 Gy given with a fractional dose of 2 Gy/day ; Treatment technique: conformal 3D. Intensity modulated radiotherapy (IMRT), also with simultaneous boost (SIB), is allowed.
cisplatin (associated to radiotherapy)Drug
Also called Cisplatin
- CDDP dose: 40 mg/mq in a single weekly 1-hour infusion preceded by adequate hydration, diuretics e antiemetic premedication.
- Radiotherapy: Doses: Clinical sites of disease (T e N) : total dose of 70 Gy given with a fractional dose of 2 Gy/day; "prophylactic" nodal volume (N) : total dose of 50 Gy given with a fractional dose of 2 Gy/day ; Treatment technique: conformal 3D. Intensity modulated radiotherapy (IMRT), also with simultaneous boost (SIB), is allowed.
| Study group | Role | What they receive |
|---|---|---|
| cetuximab plus radiotherapy | Experimental | Cetuximab given one week before radiotherapy (loading dose, 400 mg/m2) plus weekly (250 mg/m2), concomitant with radiotherapy (7O Gy on clinically involved sites). Receives: Drug: cetuximab |
| cisplatin plus radiotherapy | Active comparator | CDDP 40 mg/mq in a single weekly 1-hour infusion concomitant to radiotherapy: (70 Gy to clinically involved sites) Receives: Drug: cisplatin (associated to radiotherapy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Compliance
Evaluation and comparison of the compliance of the two treatments arms
Measured: weekly during treatment
Secondary outcomes (5)
event free survival
Evaluation and comparison of the event free survival (both local control and distant metastases)
Measured: bimonthly for two years, every 6 months thereafter
acute toxicity
Evaluation and comparison of the grade and incidence of acute toxicity.
Measured: Weekly during treatment.
Local control
Evaluation and comparison of local control
Measured: bimonthly for two years after treatment, every six months thereafter
cause specific survival
Evualation and comparison of cause specific survival
Measured: bimonthly after treatment for two years, then every 6 months
overall survival
evaluation and comperison of overall survival
Measured: bimonthly after treatment for two years, then every 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2010 (estimated)
- Study startOct 2010
- Primary completion20 May 2015
- Study completion20 May 2015
Why it stopped: insufficient recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Head and Neck NeoplasmsStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda USL 4 Prato
- Sponsor type
- University, hospital or other
- Collaborators
- Università degli Studi di Brescia
- Responsible party
- Principal investigator, STEFANO M. MAGRINI, PROF, Azienda USL 4 Prato
- Investigators
- Stefano M Magrini, Prof, Study chair, Radiotherapy Dept., Brescia Hospital and Brescia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01216020
- Sponsor's protocol ID
- eudract 2010-021552-26
- Acronym
- CTXMAB+RT
- Status last verified
- Jan 2018
- First submitted
- 6 Oct 2010
- Last updated
- 17 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Buglione M, Maddalo M, Corvo R, Pirtoli L, Paiar F, Lastrucci L, Stefanacci M, Belgioia L, Crociani M, Vecchio S, Bonomo P, Bertocci S, Borghetti P, Pasinetti N, Triggiani L, Costa L, Tonoli S, Grisanti S, Magrini SM. Subgroup Analysis According to Human Papillomavirus Status and Tumor Site of a Randomized Phase II Trial Comparing Cetuximab and Cisplatin Combined With Radiation Therapy for Locally Advanced Head and Neck Cancer. Int J Radiat Oncol Biol Phys. 2017 Mar 1;97(3):462-472. doi: 10.1016/j.ijrobp.2016.10.011. Epub 2016 Oct 20.
PubMed 27986347
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multiinstitutional Open Label Randomized Phase II Study Comparing Cetuximab and Radiotherapy Versus Cisplatin and Radiotherapy as Firstline Treatment for Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LA-NHSCC)
- ClinicalTrials.gov ID
- NCT01216020
- Acronym / sponsor ID
- CTXMAB+RT / eudract 2010-021552-26
- Keywords
- Head and Neck Cancer, Radiotherapy, Cetuximab, Cisplatin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficient recruitment
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Azienda USL 4 PratoUniversity, hospital or other
- Collaborators
- Università degli Studi di Brescia
- Study start
- Oct 2010
- Primary completion
- 20 May 2015 (actual)
- Study completion
- 20 May 2015 (actual)
- First posted
- 7 Oct 2010 (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.
BACKGROUND:
Concomitant radiotherapy and cisplatin (CDDP) based chemotherapy is the standard treatment for LA-NHSCC. This combined modality treatment is linked with considerable acute local and systemic toxicity.EGFR is overexpressed in 90-100% of the HNSCC cases and is considered an unfavourable prognostic marker. EGFR costitutive activation is linked with HNSCC pathogenesis.
Cetuximab is a monoclonal anti-EGFR antibody blocking the activation of the receptor and signal transduction. Cetuximab combined with radiotherapy is superior to radiotherapy only in the treatment of LA-HNSCC and is characterized by an acceptable toxicity profile.
RATIONALE:
A direct comparison between concomitant chemoradiotherapy with Cisplatin and the concomitant treatment with radiotherapy associated to cetuximab does not exist.
STUDY DESIGN:
Arm A: Radical radiotherapy (doses and volumes) concomitant with chemotherapy with Cisplatin (40 mg/mq/week) Arm B: Radical radiotherapy (doses and volumes) concomitant with therapy with the monoclonal antibody Cetuximab (400 mg/m2 ["loading dose"] and subsequently 250 mg /m2/week)
Detailed description
PRIMARY OBJECTIVES:
Evaluation and comparison of the compliance of the two treatments;
SECONDARY OBJECTIVES:
Evaluation and comparison of the grade and incidence of acute toxicity; Evaluation and comparison of local control; Evaluation and comparison of event free survival (both local control and distant metastases); Evaluation and comparison of cause specific and overall survival.
INCLUSION/EXCLUSION CRITERIA
- Histologically confirmed squamous cell carcinoma (biopsy obtained from the tumor and/or from its lymphnodal metastases) originating from oral cavity, oropharynx, hypopharinx, supraglottic larynx;
- Locally advanced disease, defined by one of the following criteria: every T, N+, M0 ( T1, N1 cases excluded); T3-4, N0, M0;
- Not a nasopharynx, paranasal sinuses, salivary glands tumor;
- General conditions and concomitant diseases not considered a contraindication for chemotherapy or curative radiotherapy;
- No other surgical, chemotherapeutic or radiotherapic treatments for ENT region tumors or for tumors of other anatomical sites (with the exception of non-melanoma cutaneous tumors and of the carcinoma in situ of the uterine cervix and of other solid tumors whose primary treatment has been completed more than 3 years before the accrual in this study and never relapsed since primary treatment (the patient having been since then continuously disease- free);
- Availability for follow-up;
- Signed informed consent;
- An interval of maximum 3 weeks between staging procedures for local disease and randomization
- An interval of maximum 2 weeks between randomization and the onset of the treatment
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| cetuximab plus radiotherapy | Experimental | Drug: cetuximabCetuximab given one week before radiotherapy (loading dose, 400 mg/m2) plus weekly (250 mg/m2), concomitant with radiotherapy (7O Gy on clinically involved sites). |
| cisplatin plus radiotherapy | Active comparator | Drug: cisplatin (associated to radiotherapy)CDDP 40 mg/mq in a single weekly 1-hour infusion concomitant to radiotherapy: (70 Gy to clinically involved sites) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically confirmed squamous cell carcinoma (with biopsy on the primary and / or lymph node metastases) of the oral cavity, oropharynx, hypopharynx, larynx supraglottix;
- Locally advanced disease, defined by one of the following criteria: any T, N +, M0 (excluding T1, N1), T3-4, N0, M0;
- Not cancer nasopharynx or paranasal sinuses or salivary glands;
- General conditions and associated diseases which does not allow to perform chemotherapy or radiotherapy in a radical view;
- No other surgical treatments, chemotherapy or radiotherapy for cancer of head and neck or elsewhere, except non-melanoma skin cancer or in situ cervical cancer and other solid tumors for which radical treatment has been completed > three years prior to enrollment in the study and for which the patient has remained continuously free of disease;
Key exclusion criteria (23 listed)
- Age <18 years
- ECOG performance status > 0-1
- Hemoglobin <9 g / dL
- Counts of granulocytes, total <1.5 x 10 ^ 9 / L
- Platelet count <100 x 10 ^ 9 / L
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 |
|---|---|---|
| cetuximabAlso: Erbitux* Cetuximab is given according to the standard mode of administration: "loading dose" : 400 mg/m2 one week before the start of radiotherapy (week -1), followed by a weekly dose of 250 mg/m2 during the weeks of the treatment with radiotherapy. * Radiotherapy: Doses: Clinical sites of disease (T e N) : total dose of 70 Gy given with a fractional dose of 2 Gy/day; "prophylactic" nodal volume (N) : total dose of 50 Gy given with a fractional dose of 2 Gy/day ; Treatment technique: conformal 3D. Intensity modulated radiotherapy (IMRT), also with simultaneous boost (SIB), is allowed. | Drug | cetuximab plus radiotherapy |
| cisplatin (associated to radiotherapy)Also: Cisplatin* CDDP dose: 40 mg/mq in a single weekly 1-hour infusion preceded by adequate hydration, diuretics e antiemetic premedication. * Radiotherapy: Doses: Clinical sites of disease (T e N) : total dose of 70 Gy given with a fractional dose of 2 Gy/day; "prophylactic" nodal volume (N) : total dose of 50 Gy given with a fractional dose of 2 Gy/day ; Treatment technique: conformal 3D. Intensity modulated radiotherapy (IMRT), also with simultaneous boost (SIB), is allowed. | Drug | cisplatin plus radiotherapy |
Primary outcome
Compliance
Time frame: weekly during treatment
Evaluation and comparison of the compliance of the two treatments arms
5 secondary outcomes
event free survival
Time frame: bimonthly for two years, every 6 months thereafter
acute toxicity
Time frame: Weekly during treatment.
Local control
Time frame: bimonthly for two years after treatment, every six months thereafter
cause specific survival
Time frame: bimonthly after treatment for two years, then every 6 months
overall survival
Time frame: bimonthly after treatment for two years, then every 6 months
Results and safety
The study was stopped early (reason given: insufficient recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2018.
- Derived from this study: PubMed 27986347Buglione M, Maddalo M, Corvo R, Pirtoli L, Paiar F, Lastrucci L, Stefanacci M, Belgioia L, Crociani M, Vecchio S, Bonomo P, Bertocci S, Borghetti P, Pasinetti N, Triggiani L, Costa L, Tonoli S, Grisanti S, Magrini SM. Subgroup Analysis According to Human Papillomavirus Status and Tumor Site of a Randomized Phase II Trial Comparing Cetuximab and Cisplatin Combined With Radiation Therapy for Locally Advanced Head and Neck Cancer. Int J Radiat Oncol Biol Phys. 2017 Mar 1;97(3):462-472. doi: 10.1016/j.ijrobp.2016.10.011. Epub 2016 Oct 20.
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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.
Stefano M Magrini, Prof study chair
Radiotherapy Dept., Brescia Hospital and Brescia University
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cetuximab and cisplatin (associated to radiotherapy) in people with Head and Neck Neoplasms and Laryngeal Neoplasms, run by Azienda USL 4 Prato at 7 sites in Italy.
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 9 inclusion and 23 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: stopped early, as of the sponsor's last update on 17 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Italy. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: insufficient recruitment). 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?
Compliance (time frame: weekly during treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01216020, which also lists 1 linked publication.
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 17 Jan 2018.