Head and Neck CancerPhase 1/2NCT00498953
Combination Chemotherapy and Radiation Therapy With or Without Lapatinib in Treating Patients With Locally Advanced Cancer of the Larynx or Hypopharynx
A Phase 1/2 study testing carboplatin, cisplatin and docetaxel 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: Drugs used in chemotherapy, such as docetaxel, cisplatin, fluorouracil, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- carboplatin, cisplatin and docetaxel
- Type of treatment
- Surgery or procedure
- How many people
- 7 participants
- Where
- 1 siteBelgium
- Study dates
- May 2007to Mar 2009
- Phase
- Phase 1/2
- 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 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed newly diagnosed squamous cell carcinoma of the larynx or hypopharynx
- T3 or T4 disease of the larynx or T2, T3 or T4 disease of the hypopharynx
- Nodal status must be N0, N1, N2a, N2b, N2c or N3
- Resectable or unresectable disease (Phase I patients only)
- Patient must have tumors amenable to surgery (Phase II patients only)
- No distant metastasis
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Bilirubin < 1.5 times the upper limit of the normal range
- Alkaline phosphatase and transaminases < 2.5 times the upper limit of the normal range
- Serum creatinine < 1.7 mg/dL
- All patients (male and female) must use effective contraception methods if of reproductive potential (e.g., implants, injectables, combined oral contraceptives, IUDs, sexual abstinence, or vasectomized partner)
- Females must not be pregnant or lactating
- Patients must have normal cardiac function (LVEF assessed by MUGA or ECHO) and clinically satisfactory 12-lead ECG
- No serious cardiac illness or medical condition within the past 6 months including, but not limited to, any of the following:
- History of documented congestive heart failure
- High-risk uncontrolled arrhythmias
- Angina pectoris requiring antianginal medication
- Clinically significant valvular heart disease
- Evidence of transmural infarction on ECG
- Poorly controlled hypertension (e.g., systolic BP > 180 mm Hg or diastolic BP > 100 mm Hg)
- Patients should be able to swallow oral agents
- 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 five years
- Absence of any unstable systemic diseases or active uncontrolled infections
- Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
PRIOR CONCURRENT THERAPY:
- No other prior therapy for head and neck cancer
- More than 10 days since prior and no concurrent CYP3A4 inducers, including the following:
- Antibiotics (e.g., all rifamycin class agents [rifampicin, rifabutin, or rifapentine])
- Anticonvulsants (e.g., phenytoin, carbamezepine, or barbiturates [phenobarbital])
- Oral glucocorticoids (e.g., cortisone [> 50 mg], hydrocortisone [> 40 mg], prednisone [> 10 mg], methylprednisolone [> 8 mg], or dexamethasone [> 1.5 mg])
- Antiretrovirals (e.g., efavirenz or nevirapine)
- Other (hypericum perforatum [St. John's Wort] or modafinil)
- More than 10 days since prior and no concurrent CYP3A4 inhibitors, including the following:
- Antibiotics (e.g., clarithromycin, erythromycin, or troleandomycin)
- Antifungals (e.g., itraconazole, ketoconazole, fluconazole [> 150 mg daily], or voriconazole)
- Antiretrovirals and protease inhibitors (e.g., delavirdine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, or lopinavir)
- Calcium channel blockers (e.g., verapamil or diltiazem)
- Antidepressants (e.g., nefazodone or fluvoxamine)
- Gastrointestinal agents (e.g., cimetidine or aprepitant)
- Other (e.g., grapefruit, grapefruit juice, or camiodarone)
- Miscellaneous (e.g., antacids [Mylanta, Maalox, Tums, or Rennies], all herbal [bergamottin or glabridin] or dietary supplements)
- Patients may not receive any other anticancer therapy or investigational agents while on study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II Study on Induction Chemotherapy Followed by Chemoradiation With or Without Lapatinib, a Dual EGFR/ErbB2 Kinase Inhibitor, in Patients With Locally Advanced Larynx and Hypopharynx Squamous Cell Carcinoma
RATIONALE: Drugs used in chemotherapy, such as docetaxel, cisplatin, fluorouracil, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with radiation therapy, with or without lapatinib, before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed or eliminate the need for surgery.
PURPOSE: This phase I/II trial is studying the side effects and best dose of combination chemotherapy given together with radiation therapy with or without lapatinib and to see how well it works in treating patients with locally advanced cancer of the larynx or hypopharynx.
Read the detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and recommended dose for phase II of lapatinib ditosylate in patients with locally advanced squamous cell carcinoma of the larynyx or hypopharynx who are concomitantly treated with neoadjuvant induction chemotherapy comprising docetaxel, cisplatin, and fluorouracil, followed by chemoradiotherapy comprising carboplatin and radiotherapy. (Phase I)
- To document the feasibility, in the framework of an organ preservation program, of this regimen in these patients. (Phase II)
Secondary
- To look at the role of PET in patients with N1-3 disease, in terms of PET being used as a reliable method to spare patients from planned neck dissection. (Phase II)
OUTLINE: This is a multicenter, dose-escalation phase I study followed by a randomized phase II study. Patients are stratified by institution and EGFR status (negative vs positive).
- Phase I:
- Neoadjuvant chemotherapy: Patients receive neoadjuvant chemotherapy comprising docetaxel IV and cisplatin IV on day 1 and fluorouracil IV continuously on days 1-5. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients with a complete or partial response after 4 courses of neoadjuvant chemotherapy proceed to chemoradiotherapy. Patients with less than a partial response after course 2 or course 4 proceed to surgery, including total laryngectomy.
- Chemoradiotherapy: Within 3 weeks after completion of neoadjuvant chemotherapy, patients undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 and receive carboplatin IV on days 1, 8, 15, 22, 29, 36, and 43.
- Concurrent lapatinib ditosylate: Patients receive oral lapatinib ditosylate once daily during neoadjuvant chemotherapy, during the break between neoadjuvant chemotherapy and chemoradiotherapy, and during chemoradiotherapy.
- Phase II: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive neoadjuvant chemotherapy and undergo chemoradiotherapy as in phase I.
- Arm II: Patients receive neoadjuvant chemotherapy and undergo chemoradiotherapy as in phase I. Patients also receive concurrent lapatinib ditosylate as in phase I at the recommended dose determined in phase I.
In both phases, treatment continues in the absence of disease progression or unacceptable toxicity.
Patients with node-positive disease (initially) undergo tumor and blood sample collection for biological studies. Samples are analyzed for ErbB-related activation via immunohistochemistry, in situ hybridization, and PCR/sequencing of genes/proteins, to detect DNA amplification and polysomy (for AKT, ErbB2, EGFR) and genomic losses (for PTEN) via FISH, and the ratio between EGFR and EGFRvIII via QRT-PCR. Patients with node-positive disease undergo at least elective neck dissection to evaluate the negative predictive value of PET scanning.
Patients are followed every 3 months for one year and then every 6 months thereafter.
- Conditions
- Head and Neck Cancer
- Being tested
- carboplatin, cisplatin, docetaxel, fluorouracil, lapatinib ditosylate
- Keywords
- stage II squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx
- 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.
carboplatinDrug
cisplatinDrug
docetaxelDrug
fluorouracilDrug
lapatinib ditosylateDrug
cytogenetic analysisGenetic
fluorescence in situ hybridizationGenetic
in situ hybridizationGenetic
polymerase chain reactionGenetic
reverse transcriptase-polymerase chain reactionGenetic
laboratory biomarker analysisOther
conventional surgeryProcedure or surgery
neoadjuvant therapyProcedure or surgery
fludeoxyglucose F 18Radiation
radiation therapyRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of lapatinib ditosylate (Phase I)
Dose-limiting toxicities of lapatinib ditosylate (Phase I)
Recommended dose of lapatinib ditosylate (Phase I)
Feasibility (Phase II)
Secondary outcomes (8)
Toxicity (Phase II)
Survival with functional larynx (i.e., alive without local progression/relapse, tracheotomy, feeding tube, gastrostomy, or laryngectomy) (Phase II)
Response rate (CR and PR) of neoadjuvant treatment (Phase II)
Overall response rate (Phase II)
Rate of local relapse (Phase II)
Distant metastasis (Phase II)
Overall survival (Phase II)
Predictive value of PET to spare neck dissection in N1-3 patients (Phase II)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2007 (estimated)
- Study startMay 2007
- Primary completionNov 2008
- Study completionMar 2009
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 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Ahmad Awada, MD, PhD, Study chair, Jules Bordet Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00498953
- Sponsor's protocol ID
- EORTC-24051
- Other IDs
- 2006-002667-33, GSK-EORTC-24051
- Status last verified
- Jul 2018
- First submitted
- 10 Jul 2007
- Last updated
- 9 Jul 2018
- Results posted
- No
Publications
Lalami Y, Specenier PM, Awada A, Lacombe D, Liberatoscioli C, Fortpied C, El-Hariry I, Bogaerts J, Andry G, Langendijk JA, Vermorken JB. EORTC 24051: unexpected side effects in a phase I study of TPF induction chemotherapy followed by chemoradiation with lapatinib, a dual EGFR/ErbB2 inhibitor, in patients with locally advanced resectable larynx and hypopharynx squamous cell carcinoma. Radiother Oncol. 2012 Nov;105(2):238-40. doi: 10.1016/j.radonc.2012.08.006. Epub 2012 Sep 16.
PubMed 22989664
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
- Phase I/II Study on Induction Chemotherapy Followed by Chemoradiation With or Without Lapatinib, a Dual EGFR/ErbB2 Kinase Inhibitor, in Patients With Locally Advanced Larynx and Hypopharynx Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT00498953
- Acronym / sponsor ID
- EORTC-24051
- Conditions
- Head and Neck Cancer
- Keywords
- stage II squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Study start
- May 2007
- Primary completion
- Nov 2008 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 11 Jul 2007 (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: Drugs used in chemotherapy, such as docetaxel, cisplatin, fluorouracil, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with radiation therapy, with or without lapatinib, before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed or eliminate the need for surgery.
PURPOSE: This phase I/II trial is studying the side effects and best dose of combination chemotherapy given together with radiation therapy with or without lapatinib and to see how well it works in treating patients with locally advanced cancer of the larynx or hypopharynx.
Detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and recommended dose for phase II of lapatinib ditosylate in patients with locally advanced squamous cell carcinoma of the larynyx or hypopharynx who are concomitantly treated with neoadjuvant induction chemotherapy comprising docetaxel, cisplatin, and fluorouracil, followed by chemoradiotherapy comprising carboplatin and radiotherapy. (Phase I)
- To document the feasibility, in the framework of an organ preservation program, of this regimen in these patients. (Phase II)
Secondary
- To look at the role of PET in patients with N1-3 disease, in terms of PET being used as a reliable method to spare patients from planned neck dissection. (Phase II)
OUTLINE: This is a multicenter, dose-escalation phase I study followed by a randomized phase II study. Patients are stratified by institution and EGFR status (negative vs positive).
- Phase I:
- Neoadjuvant chemotherapy: Patients receive neoadjuvant chemotherapy comprising docetaxel IV and cisplatin IV on day 1 and fluorouracil IV continuously on days 1-5. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients with a complete or partial response after 4 courses of neoadjuvant chemotherapy proceed to chemoradiotherapy. Patients with less than a partial response after course 2 or course 4 proceed to surgery, including total laryngectomy.
- Chemoradiotherapy: Within 3 weeks after completion of neoadjuvant chemotherapy, patients undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 and receive carboplatin IV on days 1, 8, 15, 22, 29, 36, and 43.
- Concurrent lapatinib ditosylate: Patients receive oral lapatinib ditosylate once daily during neoadjuvant chemotherapy, during the break between neoadjuvant chemotherapy and chemoradiotherapy, and during chemoradiotherapy.
- Phase II: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive neoadjuvant chemotherapy and undergo chemoradiotherapy as in phase I.
- Arm II: Patients receive neoadjuvant chemotherapy and undergo chemoradiotherapy as in phase I. Patients also receive concurrent lapatinib ditosylate as in phase I at the recommended dose determined in phase I.
In both phases, treatment continues in the absence of disease progression or unacceptable toxicity.
Patients with node-positive disease (initially) undergo tumor and blood sample collection for biological studies. Samples are analyzed for ErbB-related activation via immunohistochemistry, in situ hybridization, and PCR/sequencing of genes/proteins, to detect DNA amplification and polysomy (for AKT, ErbB2, EGFR) and genomic losses (for PTEN) via FISH, and the ratio between EGFR and EGFRvIII via QRT-PCR. Patients with node-positive disease undergo at least elective neck dissection to evaluate the negative predictive value of PET scanning.
Patients are followed every 3 months for one year and then every 6 months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 120 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 |
|---|---|---|
| carboplatin | Drug | – |
| cisplatin | Drug | – |
| docetaxel | Drug | – |
| fluorouracil | Drug | – |
| lapatinib ditosylate | Drug | – |
| cytogenetic analysis | Genetic | – |
| fluorescence in situ hybridization | Genetic | – |
| in situ hybridization | Genetic | – |
| polymerase chain reaction | Genetic | – |
| reverse transcriptase-polymerase chain reaction | Genetic | – |
| immunohistochemistry staining method | Other | – |
| laboratory biomarker analysis | Other | – |
| conventional surgery | Procedure or surgery | – |
| neoadjuvant therapy | Procedure or surgery | – |
| fludeoxyglucose F 18 | Radiation | – |
| radiation therapy | Radiation | – |
Primary outcome
Maximum tolerated dose of lapatinib ditosylate (Phase I)
Dose-limiting toxicities of lapatinib ditosylate (Phase I)
Recommended dose of lapatinib ditosylate (Phase I)
Feasibility (Phase II)
8 secondary outcomes
Toxicity (Phase II)
Survival with functional larynx (i.e., alive without local progression/relapse, tracheotomy, feeding tube, gastrostomy, or laryngectomy) (Phase II)
Response rate (CR and PR) of neoadjuvant treatment (Phase II)
Overall response rate (Phase II)
Rate of local relapse (Phase II)
Distant metastasis (Phase II)
Overall survival (Phase II)
Predictive value of PET to spare neck dissection in N1-3 patients (Phase II)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2018.
- Results publication: PubMed 22989664Lalami Y, Specenier PM, Awada A, Lacombe D, Liberatoscioli C, Fortpied C, El-Hariry I, Bogaerts J, Andry G, Langendijk JA, Vermorken JB. EORTC 24051: unexpected side effects in a phase I study of TPF induction chemotherapy followed by chemoradiation with lapatinib, a dual EGFR/ErbB2 inhibitor, in patients with locally advanced resectable larynx and hypopharynx squamous cell carcinoma. Radiother Oncol. 2012 Nov;105(2):238-40. doi: 10.1016/j.radonc.2012.08.006. Epub 2012 Sep 16.
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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.
Ahmad Awada, MD, PhD study chair
Jules Bordet Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing carboplatin, cisplatin and docetaxel 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: finished, 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum tolerated dose of lapatinib ditosylate (Phase I). The study lists 4 primary outcomes in all. 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 NCT00498953, 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 9 Jul 2018.