Head and Neck CancerPhase 2NCT00646659
Cetuximab, Combination Chemotherapy, and Radiation Therapy in Treating Patients With Newly Diagnosed Stage III or Stage IV Head and Neck Cancer That Cannot Be Removed By Surgery
A Phase 2 study testing cetuximab, carboplatin and cisplatin in people with Head and Neck Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 1 site in Belgium.
Trial summary
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- cetuximab, carboplatin and cisplatin
- Type of treatment
- Surgery or procedure
- How many people
- 47 participants
- Where
- 1 siteBelgium
- Study dates
- Feb 2008to Apr 2011
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed newly diagnosed squamous cell carcinoma of the head and neck
- Stage III or IV disease
- Unresectable disease
- Unidimensionally or bidimensionally measurable disease
- Skin and tumor material must be available for EGFR status and downstream signaling studies
- No nasopharyngeal, nasal, or paranasal cancer
- No distant metastases
PATIENT CHARACTERISTICS:
- WHO performance status 0-1
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Bilirubin ≤ 1.5 times the upper limit of normal (ULN)
- Alkaline phosphatase and transaminases ≤ 2.5 times ULN
- Serum creatinine ≤ 120 μmol/L (1.36 mg/dL)
- Creatinine clearance ≥ 60 mL/min
- Normal cardiac function (i.e., LVEF ≥ 50%)
- Clinically satisfactory 12-lead ECG
- No serious cardiac illness or medical condition within the past 6 months
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No current malignancies at other sites with the exception of cone-biopsied carcinoma of the cervix and adequately treated basal or squamous cell skin carcinoma or other cancer from which the patient has been disease-free for at least the past five years
- No unstable systemic diseases
- No active uncontrolled infections
- No psychological, familial, sociological, or geographical condition that would preclude compliance with the study protocol and follow-up schedule
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior treatment for head and neck cancer
- No other concurrent anticancer therapy
- No other concurrent investigational agents
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Phase II Feasibility Study of Cetuximab Combined With 4 Cycles of TPF Followed by Platinum Based Chemo-radiation Strategies
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth of tumor cells by blocking blood flow to the tumor. Radiation therapy uses high energy x- rays to kill tumor cells. Cetuximab may also make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known which regimen of radiation therapy, combination chemotherapy, and cetuximab and is most effective in treating patients with head and neck cancer.
PURPOSE: This randomized phase II trial is comparing two different regimens of radiation therapy given together with combination chemotherapy and cetuximab to see how well they work in treating patients with newly diagnosed stage III or stage IV head and neck cancer that cannot be removed by surgery.
Read the detailed description
OBJECTIVES:
- To determine the safety profile of chemoradiotherapy with carboplatin vs cisplatin in patients with newly diagnosed, unresectable stage III or IV squamous cell carcinoma of the head and neck.
- To select one of these chemoradiotherapy regimens to be used as an experimental arm in a future phase III trial.
- To look for EGFR expression and downstream signaling in reacting skin samples from patients experiencing skin toxicity and in normal skin samples from the same patients for comparison with skin samples from patients who have not shown skin toxicity.
- To explore which factors related to EGFR predict the biological activity of cetuximab in patients treated with these regimens.
OUTLINE: This is a multicenter study.
Patients receive induction chemotherapy comprising docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1 and fluorouracil IV continuously over 24 hours on days 1-5. Treatment repeats every 3 weeks for up to 4 courses in the absence of unacceptable toxicity.
Within 3 weeks after completion of induction chemotherapy or within 5 weeks from the start of the last chemotherapy course (day 21), patients are stratified by institution and treatment response (stable disease [SD], partial response [PR], or complete response [CR] vs non-response [progressive disease]). Patients with progressive disease are removed from study and patients with SD, PR, or CR are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo radiotherapy (RT) (3-dimensional conformal RT or intensity-modulated RT) on days 1-5 weekly for up to 7 weeks. Beginning on day 1 of RT, patients receive cisplatin IV over 1 hour once weekly for up to 7 weeks.
- Arm II: Patients undergo RT as in arm I. Beginning on day 1 of RT, patients receive carboplatin IV over 1 hour once weekly for up to 7 weeks.
Patients in both arms receive cetuximab IV over 1-2 hours once weekly beginning on day 1 of induction chemotherapy and continuing until the end of concurrent chemoradiotherapy.
Primary tumor tissue and skin biopsies, including fixed paraffin-embedded tissue specimens or frozen tissue, are collected at baseline (prior to treatment) and after completion of study treatment for correlative laboratory studies of EGFR expression and downstream signaling. Specimens are assessed by immunohistochemistry, fluorescence in situ hybridization, and reverse transcriptase-PCR sequencing of genes and proteins for ErbB-related activation. In the event of skin toxicity during treatment, patients undergo at least two additional biopsies, one in reacting skin and one in normal skin. Samples are assessed for markers of treatment efficacy related to cetuximab.
After completion of study therapy, patients are followed at 3 months and periodically thereafter.
- Conditions
- Head and Neck Cancer
- Being tested
- cetuximab, carboplatin, cisplatin, docetaxel, fluorouracil
- Keywords
- stage III squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the oropharynx, untreated metastatic squamous neck cancer with occult primary
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cetuximabBiological
carboplatinDrug
cisplatinDrug
docetaxelDrug
fluorouracilDrug
fluorescence in situ hybridizationGenetic
molecular genetic techniqueGenetic
reverse transcriptase-polymerase chain reactionGenetic
immunoenzyme techniqueOther
laboratory biomarker analysisOther
biopsyProcedure or surgery
3-dimensional conformal radiation therapyRadiation
intensity-modulated radiation therapyRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of the chemoradiotherapy part of the treatment, assessed as at least 80% dose intensity of any of the radiotherapy, the platinum, and cetuximab during the chemoradiotherapy part of the treatment
Secondary outcomes (4)
Toxicity as assessed by NCI CTCAE v3.0
Dose modifications
Response rate (complete or partial response)
EGFR expression and downstream signaling in primary tumor and in skin samples
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2008 (estimated)
- Study startFeb 2008
- Primary completionMay 2010
- Study completionApr 2011
Why it stopped: Recruitment was suspended prematurely for safety concerns and closed after IDMC review
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Jan B. Vermorken, MD, PhD, Principal investigator, University Hospital, Antwerp
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00646659
- Sponsor's protocol ID
- EORTC-24061
- Other IDs
- MERCK-EORTC-24061, SANOFI-AVENTIS-EORTC-24061, 2006-004189-14
- Status last verified
- Jul 2018
- First submitted
- 27 Mar 2008
- Last updated
- 9 Jul 2018
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Feasibility Study of Cetuximab Combined With 4 Cycles of TPF Followed by Platinum Based Chemo-radiation Strategies
- ClinicalTrials.gov ID
- NCT00646659
- Acronym / sponsor ID
- EORTC-24061
- Conditions
- Head and Neck Cancer
- Keywords
- stage III squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the oropharynx
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment was suspended prematurely for safety concerns and closed after IDMC review
- Enrolment
- 47 participants (actual)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Study start
- Feb 2008
- Primary completion
- May 2010 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 28 Mar 2008 (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.
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth of tumor cells by blocking blood flow to the tumor. Radiation therapy uses high energy x- rays to kill tumor cells. Cetuximab may also make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known which regimen of radiation therapy, combination chemotherapy, and cetuximab and is most effective in treating patients with head and neck cancer.
PURPOSE: This randomized phase II trial is comparing two different regimens of radiation therapy given together with combination chemotherapy and cetuximab to see how well they work in treating patients with newly diagnosed stage III or stage IV head and neck cancer that cannot be removed by surgery.
Detailed description
OBJECTIVES:
- To determine the safety profile of chemoradiotherapy with carboplatin vs cisplatin in patients with newly diagnosed, unresectable stage III or IV squamous cell carcinoma of the head and neck.
- To select one of these chemoradiotherapy regimens to be used as an experimental arm in a future phase III trial.
- To look for EGFR expression and downstream signaling in reacting skin samples from patients experiencing skin toxicity and in normal skin samples from the same patients for comparison with skin samples from patients who have not shown skin toxicity.
- To explore which factors related to EGFR predict the biological activity of cetuximab in patients treated with these regimens.
OUTLINE: This is a multicenter study.
Patients receive induction chemotherapy comprising docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1 and fluorouracil IV continuously over 24 hours on days 1-5. Treatment repeats every 3 weeks for up to 4 courses in the absence of unacceptable toxicity.
Within 3 weeks after completion of induction chemotherapy or within 5 weeks from the start of the last chemotherapy course (day 21), patients are stratified by institution and treatment response (stable disease [SD], partial response [PR], or complete response [CR] vs non-response [progressive disease]). Patients with progressive disease are removed from study and patients with SD, PR, or CR are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo radiotherapy (RT) (3-dimensional conformal RT or intensity-modulated RT) on days 1-5 weekly for up to 7 weeks. Beginning on day 1 of RT, patients receive cisplatin IV over 1 hour once weekly for up to 7 weeks.
- Arm II: Patients undergo RT as in arm I. Beginning on day 1 of RT, patients receive carboplatin IV over 1 hour once weekly for up to 7 weeks.
Patients in both arms receive cetuximab IV over 1-2 hours once weekly beginning on day 1 of induction chemotherapy and continuing until the end of concurrent chemoradiotherapy.
Primary tumor tissue and skin biopsies, including fixed paraffin-embedded tissue specimens or frozen tissue, are collected at baseline (prior to treatment) and after completion of study treatment for correlative laboratory studies of EGFR expression and downstream signaling. Specimens are assessed by immunohistochemistry, fluorescence in situ hybridization, and reverse transcriptase-PCR sequencing of genes and proteins for ErbB-related activation. In the event of skin toxicity during treatment, patients undergo at least two additional biopsies, one in reacting skin and one in normal skin. Samples are assessed for markers of treatment efficacy related to cetuximab.
After completion of study therapy, patients are followed at 3 months and periodically thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| cetuximab | Biological | – |
| carboplatin | Drug | – |
| cisplatin | Drug | – |
| docetaxel | Drug | – |
| fluorouracil | Drug | – |
| fluorescence in situ hybridization | Genetic | – |
| molecular genetic technique | Genetic | – |
| reverse transcriptase-polymerase chain reaction | Genetic | – |
| immunoenzyme technique | Other | – |
| immunohistochemistry staining method | Other | – |
| laboratory biomarker analysis | Other | – |
| biopsy | Procedure or surgery | – |
| 3-dimensional conformal radiation therapy | Radiation | – |
| intensity-modulated radiation therapy | Radiation | – |
Primary outcome
Feasibility of the chemoradiotherapy part of the treatment, assessed as at least 80% dose intensity of any of the radiotherapy, the platinum, and cetuximab during the chemoradiotherapy part of the treatment
4 secondary outcomes
Toxicity as assessed by NCI CTCAE v3.0
Dose modifications
Response rate (complete or partial response)
EGFR expression and downstream signaling in primary tumor and in skin samples
Results and safety
The study was stopped early (reason given: Recruitment was suspended prematurely for safety concerns and closed after IDMC review). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2018.
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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.
Jan B. Vermorken, MD, PhD principal investigator
University Hospital, Antwerp
1 site 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, carboplatin and cisplatin in people with Head and Neck Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 9 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. 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: Recruitment was suspended prematurely for safety concerns and closed after IDMC review). 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?
Feasibility of the chemoradiotherapy part of the treatment, assessed as at least 80% dose intensity of any of the radiotherapy, the platinum, and cetuximab during the chemoradiotherapy part of the treatment. 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 9 Jul 2018.