Combination Chemotherapy and Radiation Therapy With or Without Lapatinib in Treating Patients With Locally Advanced Cancer of the Larynx or Hypopharynx

NCT00498953 | Completed Phase 1

• 3 other identifiers: EORTC-240512006-002667-33GSK-EORTC-24051
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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. 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.

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

Outcome Measures

Primary Outcomes (4)

• 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)

Interventions

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

neoadjuvant therapy PROCEDURE

fludeoxyglucose F 18 RADIATION

radiation therapy RADIATION

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (1)

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Related Publications (1)

• 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.

  PMID: 22989664 RESULT

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Carboplatin; Cisplatin; Docetaxel; Fluorouracil; Lapatinib; Cytogenetic Analysis; In Situ Hybridization, Fluorescence; In Situ Hybridization; Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Immunohistochemistry; Neoadjuvant Therapy; Fluorodeoxyglucose F18; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Staining and Labeling; Histocytological Preparation Techniques; Histological Techniques; Nucleic Acid Hybridization; Nucleic Acid Amplification Techniques; Histocytochemistry; Immunologic Techniques; Combined Modality Therapy; Therapeutics; Deoxyglucose; Deoxy Sugars; Carbohydrates

Study Officials

• Ahmad Awada, MD, PhD

  Jules Bordet Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2007
• First Posted: July 11, 2007
• Study Start: May 1, 2007
• Primary Completion: November 1, 2008
• Study Completion: March 1, 2009
• Last Updated: July 9, 2018

Record last verified: 2018-07

Locations

BE (1)