Lapatinib Versus Placebo Given Concurrently With Cisplatin And Radiotherapy In Patients With Unresected Head And Neck Cancer

NCT00387127 | Completed Phase 2 Results DMC

• 1 other identifier: EGF105884
• Study Type: interventional
• Target: 67
• Locations: 9 countries
• Sites: 30

Brief Summary

This is a phase II study comparing the effects of lapatinib versus placebo when administered concurrently with cisplatin and radiotherapy followed by 1 year monotherapy with lapatinib or placebo. The study is designed to evaluate and compare the two treatment groups with respect to complete response rate at 6 months following chemoradiation completion.

Conditions

Neoplasms, Head and Neck

Keywords

Neck Cancer; Locally advanced head and neck cancer; locally advanced; Head and Neck cancer; lapatinib; EGFR/ErbB2 inhibitor; Head Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants (Par.) With Complete Response (CR), as Assessed by Independent Radiological Review

  Participants with CR are defined as those who achieved a complete tumor response at 6 months after the completion of the chemoradiation treatment (CRT), as assessed by independent radiological review. Tumor response was assessed using modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Per RECIST, CR is defined as the disappearance of all target and non-target lesions. Data are based on Week 24 scans from participants receiving study treatment at that time and on those in follow-up.

  From the date of randomization until 6 months post chemoradiation treatment, assessed for a median time of 13 months

Secondary Outcomes (16)

• Number of Participants With CR, as Assessed by the Investigator

  From the date of randomization until 6 months post chemoradiation treatment, assessed after a median time of 13 months of follow-up

• Progression-Free Survival (PFS), as Assessed by the Investigator

  From the date of randomization until the date of disease progression or death due to any cause, assessed after a median of 22 months of follow-up

• Overall Survival (OS)

  From the date of randomization until the date of death due to any cause, assessed after a median of 30.9 months

• Number of Participants Who Died Due to Progressive Disease

  From the date of randomization until the date of death due to disease under study, assessed after a median of 30.9 months

• Disease-specific Survival

  From the date of randomization until the date of death due to disease, assessed after a median of 13 months of follow-up

Other Outcomes (1)

• Number of Participants Classified as Responders, as Per Volumetric Tumor Response

  From the date of randomization until 6 months post chemoradiation treatment, assessed for a median of 13 months

Study Arms (2)

Lapatinib

EXPERIMENTAL

1500mg lapatinib orally daily

Drug: Lapatinib oral tablets; Drug: radiotherapy; Drug: cisplatin chemotherapy

Placebo

PLACEBO COMPARATOR

orally daily

Drug: Lapatinib oral tablets; Drug: radiotherapy; Drug: cisplatin chemotherapy

Interventions

Lapatinib oral tablets DRUG

Lapatinib is administered orally once daily.

Lapatinib; Placebo

radiotherapy DRUG

Radiotherapy is given either as conventional fractionation using Two-dimensional (2D) or conformal techniques, or as Intensity Modulated Radiation Therapy (IMRT). Radiation therapy will be standardised throughout the study. Radiation therapy is given only once daily, with a dose/fraction not exceeding 2.5Gy, to a total dose of 65 Gy (IMRT) or 70 Gy (2D or 3D RT) to the gross site of disease .

Lapatinib; Placebo

cisplatin chemotherapy DRUG

Cisplatin is administered intravenously at a dose of 100mg/m2 on days 1, 22 and 43 of radiotherapy (approximately Study Days 8, 29 and 50).

Also known as: radiotherapy, Lapatinib oral tablets

Lapatinib; Placebo

Eligibility Criteria

• Age: 18 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 or more of the following sites:
• oral cavity, oropharynx, hypopharynx and larynx;
• Multiple primary tumours will:
• Have to be histologically proven; Have to be anatomically distant and surrounded by normal tissue; Exclude distant metastasis.
• Prior to enrolment subjects must have ErbB1 over-expression determined by immunohistochemistry (IHC) 3+ as assessed by a central laboratory;
• Subjects with stage III and IVA/IVB disease, who are to receive cisplatin chemotherapy and radiation therapy as primary treatment (total dose 65 - 70 Gy); Subjects with any Tis, T1 or T2 disease regardless of N stage, are excluded. Subjects with distant metastases, ie Stage IVC, are excluded.
• Willing and able to have a tumour biopsy taken at screening; For patients who have had prior tumour biopsy, an adequate archived specimen must be available.
• Male or female ≥18 years of age;
• Criteria for female subjects or female partners of male subjects:
• Non-child-bearing potential (i.e., women with functioning ovaries who have a GM2005/00448/00 CONFIDENTIAL EGF105884 22 current documented tubal ligation or hysterectomy, or women who are postmenopausal); Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility.) This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate. These subjects must have a negative serum pregnancy test at screening and agree to one of the following: Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; or Consistent and correct use of one of the following acceptable methods of birth control: male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; implants of levonorgestrel; injectable progestogen; any intrauterine device (IUD) with a documented failure rate of less than
• % per year; oral contraceptives (either combined or progestogen only); or barrier methods, including diaphragm or condom with a spermicide.
• ECOG performance status 0, 1 or 2;
• Subjects must have adequate haematological, renal and hepatic function; Calculated creatinine clearance ≥50 ml/min as determined by the modified method of Cockcroft and Gault or by the EDTA method. Absolute neutrophil count ≥1,500/μl, platelets ≥100,000/μl. Haemoglobin ≥9gm/dL (5mmol/L). Aspartate (AST) and alanine transaminase (ALT) less than 4 times the upper limit of the normal range (ULN). Total bilirubin ≤2.0 mg/dL.
• Left ventricular ejection fraction (LVEF) within the institutional normal ranges as measured by echocardiogram (ECHO) or Multigated Acquisition (MUGA) scan;

You may not qualify if:

• Nasopharyngeal, paranasal sinuses or nasal cavity tumours;
• Any prior or current treatment for invasive head and neck cancer of any kind. This will include but is not limited to: prior tyrosine kinase inhibitors, prior neoadjuvant therapy, prior surgical resection, or use of any investigational agent;
• Concurrent use of CYP3A4 inducers or inhibitors. A standard 3-day course of dexamethasone for the prevention of cisplatin-induced nausea and vomiting is permitted;
• Subjects with known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure;
• 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, including in the head and neck region that was successfully treated with surgery, photodynamics or laser, will be permitted;
• Peripheral neuropathy ≥ grade 2;
• Pregnant or lactating females (female subjects of child-bearing potential will undertake pregnancy testing at screening and during study completion/withdrawal visits);
• Malabsorption syndrome, disease significantly affecting GI function, that could affect absorption of lapatinib;
• History of allergic reactions to appropriate antiemetics (e.g. 5-HT3 antagonists) to be administered with platinum chemotherapy;
• 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 (30)

GSK Investigational Site

Minneapolis, Minnesota, 55417, United States

Location

GSK Investigational Site

Kansas City, Missouri, 64128, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28203, United States

Location

GSK Investigational Site

Hamilton, Ontario, L8V 5C2, Canada

Location

GSK Investigational Site

Québec, Quebec, G1R 2J6, Canada

Location

GSK Investigational Site

Sherbrooke, Quebec, J1H 5N4, Canada

Location

GSK Investigational Site

Lens, 62307, France

Location

GSK Investigational Site

Lille, 59000, France

Location

GSK Investigational Site

Lyon, 69437, France

Location

GSK Investigational Site

Paris, 75908, France

Location

GSK Investigational Site

Vandœuvre-lès-Nancy, 54511, France

Location

GSK Investigational Site

Budapest, 1122, Hungary

Location

GSK Investigational Site

Győr, 9023, Hungary

Location

GSK Investigational Site

Ahemdabad, 380016, India

Location

GSK Investigational Site

Mumbai, 400012, India

Location

GSK Investigational Site

Thiruvananthapuram, 695011, India

Location

GSK Investigational Site

Amsterdam, 1066 CX, Netherlands

Location

GSK Investigational Site

Leiden, 2333 ZA, Netherlands

Location

GSK Investigational Site

Lima, Lima Province, Lima 11, Peru

Location

GSK Investigational Site

Lima, Lima Province, Lima 34, Peru

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

GSK Investigational Site

Northwood, Middlesex, HA6 2RN, United Kingdom

Location

GSK Investigational Site

Coventry, CV2 2DX, United Kingdom

Location

GSK Investigational Site

Leeds, LS9 7TF, United Kingdom

Location

GSK Investigational Site

London, EC1A 7BE, United Kingdom

Location

GSK Investigational Site

London, SW3 6JJ, United Kingdom

Location

GSK Investigational Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

GSK Investigational Site

Sheffield, S10 2SJ, United Kingdom

Location

Related Publications (2)

• Harrington K, Berrier A, Robinson M, Remenar E, Housset M, de Mendoza FH, Fayette J, Mehanna H, El-Hariry I, Compton N, Franklin N, Biswas-Baldwin N, Lau M, Legenne P, Kumar R. Randomised Phase II study of oral lapatinib combined with chemoradiotherapy in patients with advanced squamous cell carcinoma of the head and neck: rationale for future randomised trials in human papilloma virus-negative disease. Eur J Cancer. 2013 May;49(7):1609-18. doi: 10.1016/j.ejca.2012.11.023. Epub 2012 Dec 19.

  PMID: 23265705 BACKGROUND

• Psyrri A, Rampias T, Vermorken JB. The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck. Ann Oncol. 2014 Nov;25(11):2101-2115. doi: 10.1093/annonc/mdu265. Epub 2014 Jul 23.

  PMID: 25057165 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Lapatinib; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Therapeutics

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 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2006
• First Posted: October 12, 2006
• Study Start: November 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: January 1, 2014
• Last Updated: June 25, 2015
• Results First Posted: January 5, 2015

Record last verified: 2015-02

Locations

ES (2); US (3); HU (2); IN (3); CA (3); PE (2); NL (2); GB (8); FR (5)