Study Of Adjuvant Lapatinib In High-Risk Head And Neck Cancer Subjects After Surgery

NCT00424255 | Completed Phase 3 Results

• 1 other identifier: EGF102988
• Study Type: interventional
• Target: 688
• Locations: 21 countries
• Sites: 98

Brief Summary

This is a randomised, double-blind, placebo-controlled, multicentre, global Phase III trial comparing the efficacy of adjuvant oral lapatinib versus placebo in high-risk subjects with head and neck cancer following surgery. Lapatinib or placebo will be administered post-operatively in combination with chemoradiotherapy followed by maintenance with lapatinib or placebo for 1 year. The primary goal is to determine if lapatinib is effective at reducing the recurrence of the disease in these high-risk patients.

Conditions

Neoplasms, Head and Neck

Keywords

Cancer of the Head and Neck; Neck cancer; Adjuvant; Head and neck cancer; High-risk head and neck cancer; Post-surgery; Head cancer

Outcome Measures

Primary Outcomes (1)

• Disease Free Survival (DFS)

  DFS is defined as the time from randomization until the earliest date of disease recurrence (evidence of local, regional, or distant disease progression, second primary tumor) or death due to any cause. Disease recurrence was based on the assessments from the blinded, independent reviewer (radiological and clinical). Participants who initiated alternative anti-cancer therapy prior to disease recurrence or death were treated as censored at the last assessment prior to the time of this initiation. For participants whose disease did not recur or who did not die, DFS was censored at the time of the last independently assessed radiological scan (where initiation of alternative anti-cancer therapy had not commenced). Participants who missed two or more consecutive disease assessments were censored at the last assessment prior to the missed assessments. Participants considered to have malignant disease at Baseline were censored at the time of randomization.

  From randomization until the earliest date of disease recurrence or death due to any cause (average of 101 study weeks)

Secondary Outcomes (20)

• Overall Survival (OS)

  From randomization until death due to any cause (average of 131 study weeks)

• Disease Specific Survival (DSS)

  From randomization until death due to head and neck cancer (average of 131 study weeks)

• Time to Locoregional Recurrence (TTLR)

  From randomization until thefirst occurrence that local and/or regional recurrence is documented or the date of censor (average of 101 study weeks)

• Time to Distant Relapse (TTDR)

  From randomization until the first documented occurrence that distant relapse is documented (average of 101 study weeks)

• Number of Participants With a Second Primary Tumor

  From randomization until development of second primary tumor or within 28 days of first recurrence (average of 101 study weeks)

Study Arms (2)

Lapatinib+Chemoradiation

EXPERIMENTAL

Adjuvant concurrent chemoradiotherapy plus lapatinib 1500 mg once daily for 6 to 7 weeks, followed by lapatinib 1500 mg once daily for one year. Chemoradiotherapy=total dose of 66Gy over 6-7 weeks plus cisplatin 100mg/m2 on days 1,2 and 43 of the course of radiotherapy. Lapatinib is also given at 1500 mg once daily for 3-7 days prior to the start of chemoradiotherapy.

Drug: Lapatinib

Placebo+Chemoradiation

PLACEBO COMPARATOR

Adjuvant concurrent chemoradiotherapy plus placebo once daily for 6 to 7 weeks, followed by placebo once daily for one year. Chemoradiotherapy = total dose of 66Gy over 6-7 weeks plus cisplatin 100mg/m2 on days 1,2 and 43 of the course of treatment. Placebo is also given once daily for 3-7 days prior to the start of chemoradiotherapy.

Radiation: Chemoradiation; Other: Placebo

Interventions

Lapatinib DRUG

Dual ErbB1/2 inhibitor

Lapatinib+Chemoradiation

Chemoradiation RADIATION

Radiation plus platinum based chemotherapy

Placebo+Chemoradiation

Placebo OTHER

Placebo

Placebo+Chemoradiation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to sign a written informed consent.
• Histologically confirmed diagnosis of SCCHN of one of the following sites: oral cavity, oropharynx, hypopharynx and larynx.
• Pathological Stage II, III or IVa (according to AJCC cancer staging criteria \[Green, 2002\]) with no evidence of gross residual disease, and at least one of the following high risk factors by pathology:
• Extracapsular extension of nodal disease
• Positive resection margin (5 mm or less)
• Primary surgery with a curative intent completed within 4-6 weeks (and no later than 7 weeks) prior to randomization. The extent of surgical resection will follow accepted criteria for adequate excision \[Helliwell, 2005\]. Surgical margins are divided into 'mucosal' and 'deep', and for each category the resection margin (R) is classified as:
• Clear : (R0) \> 5mm.
• Close: (R1) 1 - 5mm.
• Involved: (R2) \<1mm
• Complete recovery from the surgical procedure allowing for appropriate radiotherapy. Radiation therapy is required to start as soon as adequate healing has occurred. This is normally around 4-6 weeks but no later than 9 weeks after surgery.
• Adequate tumour specimen from archived or resected tissue must be available for IHC evaluation of ErbB1 expression levels in a central laboratory and subsequent biomarker analysis.
• Male or female, between 18 and 70 years of age \[Bourhis, 2006\].
• Criteria for female subjects or female partners of male subjects:
• Non-child-bearing potential (i.e., a woman with functioning ovaries who has a current documented tubal ligation or hysterectomy or a woman who is menopausal); or
• Child-bearing potential (i.e. a woman with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility. This category includes women with oligomenorrhoea (even severe), women who are perimenopausal and young women who have begun to menstruate), who have a negative serum pregnancy test at screening, and agree to one of the following:

You may not qualify if:

• Nasopharyngeal, paranasal sinuses or nasal cavity tumours
• Head and neck cancer with histology other than squamous cell carcinoma.
• Evidence of distant metastases or gross post-operative residual disease.
• Evidence of second primary tumour.
• Any prior or current anticancer treatment of any kind - except the primary surgical resection. This will include but is not limited to: prior tyrosine kinase inhibitors, prior neoadjuvant therapy, prior radiotherapy or use of any investigational agent.
• Concurrent treatment with an investigational agent or participation in another clinical trial.
• Concurrent use of CYP3A4 inducers or inhibitors while on lapatinib/placebo. A standard 3 to 5 day course of dexamethasone for the prevention of cisplatin induced nausea and vomiting is permitted. In addition glucocorticoid daily doses (oral) 1.5mg dexamethasone (or equivalent) are allowed.
• Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure;
• Pregnant or lactating females
• History of another malignancy within the last 5 years, with the exception of completely resected basal or squamous cell skin cancer, or successfully treated in-situ carcinoma. History of non-invasive lesion or in-situ carcinoma, that was successfully treated with surgery, photodynamics or laser, will be permitted;
• Peripheral neuropathy ≥ grade 2
• Mal-absorption syndrome, disease significantly affecting GI function, or major resection of the stomach or bowel, that could affect absorption of lapatinib.
• History of allergic reactions to relevant diuretics or anti-emetics (e.g 5-HT3 antagonists) to be administered with cisplatin chemotherapy
• History of allergic reactions attributed to compounds of similar chemical composition (quinazolines) to lapatinib
• The investigator considers the subject unfit for the study as a result of the medical interview, physical examinations, or screening investigations

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (117)

GSK Investigational Site

Springfield, Illinois, 62794, United States

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St Louis, Missouri, 63110, United States

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New York, New York, 10003, United States

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Chapel Hill, North Carolina, 27599-7600, United States

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Lubbock, Texas, 79415, United States

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Ciudad Autonoma de Buenos Aires, Buenos Aires, C1185AAT, Argentina

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Rosario, Santa Fe Province, S2000KZE, Argentina

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Santa Fe, Santa Fe Province, 3000, Argentina

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Quilmes, 1878, Argentina

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Innsbruck, A-6020, Austria

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Rankweil, A-6830, Austria

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Salzburg, A-5020, Austria

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Vienna, 1130, Austria

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Vienna, A-1090, Austria

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Edmonton, Alberta, T6G 1Z2, Canada

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Halifax, Nova Scotia, B3H 1V7, Canada

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London, Ontario, N6A 4L6, Canada

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Québec, Quebec, G1R 2J6, Canada

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Sherbrooke, Quebec, J1H 5N4, Canada

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Guangzhou, Guangdong, 510060, China

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Wuhan, Hubei, 430030, China

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Beijing, 100021, China

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Beijing, 100036, China

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Fuzhou, 350014, China

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Shanghai, 200032, China

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Tianjin, 300060, China

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Zagreb, 10 000, Croatia

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Zagreb, 10000, Croatia

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Brno, 65691, Czechia

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Olomouc, 775 20, Czechia

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Ostrava - Poruba, 708 52, Czechia

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Prague, 180 00, Czechia

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Tallinn, 13419, Estonia

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Angers, 49933, France

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Annecy, 74000, France

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Caen, 14033, France

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Colmar, 68024, France

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Férolles-Attilly, 77150, France

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La Roche-sur-Yon, 85025, France

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Lille, 59000, France

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Lyon, 69008, France

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Montpellier, 34298, France

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Paris, 75970, France

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Reims, 51100, France

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Saint-Cloud, 92210, France

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Strasbourg, 67085, France

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Toulouse, 31052, France

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Villejuif, 94805, France

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Heidelberg, Baden-Wurttemberg, 69120, Germany

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Karlsruhe, Baden-Wurttemberg, 76135, Germany

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Essen, North Rhine-Westphalia, 45122, Germany

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Dresden, Saxony, 01067, Germany

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Leipzig, Saxony, 04103, Germany

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Halle, Saxony-Anhalt, 06097, Germany

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Athens, 142 33, Greece

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Athens, 15125, Greece

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Haidari, Athens, 12462, Greece

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Neo Faliro, 18547, Greece

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Peiraius, 185 37, Greece

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Hong Kong, Hong Kong

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Kowloon, Hong Kong

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Budapest, 1115, Hungary

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Budapest, 1122, Hungary

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Szombathely, 9700, Hungary

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Kochi, 682026, India

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Mumbai, 400 016, India

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Mumbai, 400012, India

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Pune, 411001, India

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Trivandrum, 695011, India

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Galway, Ireland

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Rathgar, Dublin, 6, Ireland

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Napoli, Campania, 80131, Italy

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Genoa, Liguria, 16132, Italy

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Milan, Lombardy, 20132, Italy

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Milan, Lombardy, 20141, Italy

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Pavia, Lombardy, 27100, Italy

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Venezia, Veneto, 30122, Italy

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Manila, 1000, Philippines

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Moscow, 115478, Russia

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Moscow, 129128, Russia

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Saint Petersburg, 198255, Russia

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Ufa, 450054, Russia

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Bratislava, 812 50, Slovakia

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Košice, 041 91, Slovakia

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Barcelona, 08025, Spain

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Barcelona, 08035, Spain

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Córdoba, 14004, Spain

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Girona, 17007, Spain

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Granada, 18014, Spain

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Huesca, 22300, Spain

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Lleida, 25198, Spain

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Madrid, 28033, Spain

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Madrid, 28034, Spain

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Madrid, 28040, Spain

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Madrid, 28041, Spain

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Madrid, 28046, Spain

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Murcia, 30008, Spain

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Ourense, 32005, Spain

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Santander, 39008, Spain

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Santiago de Compostela, 15706, Spain

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Seville, 41009, Spain

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Valencia, 46009, Spain

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Zaragoza, 50009, Spain

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Chiang Mai, 50200, Thailand

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Cambridge, Cambridgeshire, CB2 2QQ, United Kingdom

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Northwood, Middlesex, HA6 2RN, United Kingdom

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Edinburgh, Midlothian, EH4 2XU, United Kingdom

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Brighton, Sussex East, BN2 5BE, United Kingdom

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Guildford, GU2 7XX, United Kingdom

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London, NW1 2PG, United Kingdom

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London, SE1 7EH, United Kingdom

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London, SW3 6JJ, United Kingdom

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Newcastle upon Tyne, NE7 7DN, United Kingdom

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Sheffield, S10 2SJ, United Kingdom

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Sutton, SM2 5PT, United Kingdom

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Related Publications (3)

• Sunkara PR, Chow E, Waitzman J, Sukari A, Cramer JD. The Prognostication of Surgically Resected Head and Neck Squamous Cell Carcinoma Using Pre-Therapy Neutrophil and Lymphocyte Counts. Head Neck. 2025 Feb;47(2):687-694. doi: 10.1002/hed.27949. Epub 2024 Oct 16.

  PMID: 39415507 DERIVED

• Sunkara PR, Graff JT, Cramer JD. Association of Surgical Margin Distance With Survival in Patients With Resected Head and Neck Squamous Cell Carcinoma: A Secondary Analysis of a Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2023 Apr 1;149(4):317-326. doi: 10.1001/jamaoto.2022.5186.

  PMID: 36821132 DERIVED

• Harrington K, Temam S, Mehanna H, D'Cruz A, Jain M, D'Onofrio I, Manikhas G, Horvath Z, Sun Y, Dietzsch S, Dubinsky P, Holeckova P, El-Hariry I, Franklin N, Biswas-Baldwin N, Legenne P, Wissel P, Netherway T, Farrell J, Ellis C, Wang-Silvanto J, Amonkar M, Ahmed N, Santillana S, Bourhis J. Postoperative Adjuvant Lapatinib and Concurrent Chemoradiotherapy Followed by Maintenance Lapatinib Monotherapy in High-Risk Patients With Resected Squamous Cell Carcinoma of the Head and Neck: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study. J Clin Oncol. 2015 Dec 10;33(35):4202-9. doi: 10.1200/JCO.2015.61.4370. Epub 2015 Nov 2.

  PMID: 26527790 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Lapatinib; Chemoradiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2007
• First Posted: January 19, 2007
• Study Start: December 1, 2006
• Primary Completion: March 1, 2013
• Study Completion: November 1, 2013
• Last Updated: July 18, 2014
• Results First Posted: February 11, 2014

Record last verified: 2014-06

Locations

CR (2); AR (4); CA (5); FR (15); ES (1); CZ (4); CN (7); HK (2); DE (6); IN (5); RU (4); HU (3); GB (11); IE (2); AU (5); TH (3); IT (6); SL (2); PH (1); US (5); GR (5)