Entry Detail
| General information | |
| Database: | DB00360 |
| Objective: | afatinib |
| Authors: | Burtness B, et al |
| Title: | Afatinib versus placebo as adjuvant therapy after chemoradiation in a doubleblind, phase III study (LUXHead & Neck 2) in patients with primary unresected, clinically intermediatetohighrisk head and neck cancer: study protocol for a randomized controlled trial. |
| Journal: | Trials. |
| Year: | 2014 |
| PMID: | 25432788 |
| Trial Design | |
| Clinical Trial Id: | NCT01345669 |
| Agent: | afatinib |
| Target: | Receptor proteintyrosine kinase erbB2 Epidermal growth factor receptor |
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 4 |
| Therapeutic Combination Content: | Afatinib versus placebo as adjuvant therapy after chemoradiation |
| Study Type: | randomized, multicentre, doubleblind, placebocontrolled, phase III trial |
| Key Patients Feature: | Eligible patients must be more than and equal to 18 years of age, have anECOG performance status of 0 or 1 and have histologically or cytologically confirmed locoregionally advancedHNSCC at the time of randomization (stage III, IVa orIVb squamous cell carcinoma of the oral cavity, oropharynx or hypopharynx, or stage IVa or IVb squamous cellcarcinoma of the larynx). Patients are required to haveunresected disease prior to chemoradiotherapy and anunfavourable risk of recurrence. Patients can have unresected disease for the following reasons: (1) they mayhave technically unresectable disease owing to tumourfixation, or invasion to either base of the skull, cervicalvertebrae, nasopharynx or fixed lymph nodes; (2) theremay be low surgical curability (T3 or T4, N2 or N3 excluding T1N2, based on the TNM Staging Classificationfor Head and Neck Cancers) [8]; or (3) patients may betreated for organ preservation. As HPV status will notbe determined for eligibility in this study, unfavourablerisk is defined as nonoropharynx primary site or oropharynx cancer in heavy smokers (>10 packyears). Patientsmust also have completed prior definitive platinumbasedchemoradiotherapy by no longer than 24 weeks prior torandomization (at least two cycles of cisplatin at a minimum cumulative dose of 200 mg/m2 or carboplatin at aminimum cumulative area under the concentrationtimecurve of 9; radiotherapy of minimum 66 Gy in 33 fractions(or its radiobiological equivalent)), and at randomizationhave chemoradiotherapyinduced adverse events classifiedas less than or equal to grade 2 using the CommonTerminology Criteria for Adverse Events. Patients are required to have no evidence of disease after chemoradiotherapy (that is, no residual tumour after chemoradiotherapy, or no residual tumour after chemoradiotherapy followed byR0 tumour resection, or no evidence of nodal disease afterchemoradiotherapy followed by neck dissection). Patientsmust also have adequate bone marrow, liver and kidneyfunction. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | A:afatinib B:placebo |
| Treatment Info: | Pts will be randomized 2:1 to oral oncedaily afatinib (40 mg starting dose) or placebo. Treatment will continue for 18 months or until recurrence or unacceptable adverse events occur. |
| Primary End Point: | duration of diseasefree survival; |
| Secondary End Point: | diseasefree survival rate at 2 years, overall survival, healthrelated quality of life and safety. |
| Patients Number: | 669 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | Given the unmet need in the adjuvant treatment of intermediatetohighrisk HNSCC patients, it is expected that LUXHead & Neck 2 will provide new insights into treatment in this setting and might demonstrate the ability of afatinib to significantly improve diseasefree survival, compared with placebo. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | protocol |