Clinical trial NCT01732640: A Phase I/II Study Afatinib/Carboplatin/Paclitaxel Induction Chemotherapy In HPV-Negative HNSCC.
Official title: A Phase I/II Study Afatinib/Carboplatin/Paclitaxel Induction Chemotherapy Followed By Standard Chemoradiation In HPV-Negative or High-risk HPV-Positive Locally Advanced Stage III/IVa/IVb HNSCC
Conditions: Squamous Cell Carcinoma of the Head and Neck
Summary: Trial Objectives:
The objective is to investigate the efficacy and safety of afatinib with induction chemotherapy in primary unresected patients with locally advanced, HPV-negative, stage III or IVa/b HNSCC including oral cavity, oropharynx, hypopharynx, or larynx.
Primary Objective Phase I The primary objective of the phase I portion of the trial is to determine the maximum tolerated dose (MTD) or the recommended phase II dose of daily oral afatinib that is safe in combination with carboplatin AUC 6 and paclitaxel 175mg/m2 q 21 days as an induction regimen.
Primary Objective Phase 2 The primary objective of the phase 2 portion of the trial is to estimate the objective tumor response rate and toxicity with induction therapy in patients treated on the afatinib dose determined in Phase I.
Secondary Objectives The secondary objective of phase II is to estimate: 1) the overall response to entire treatment after completion of CRT, 2) progression-free survival (PFS) rate at 2 years, and 3) overall survival (OS) at 2 years.
Interventions:
description: Afatinib will be supplied as film-coated tablets. Available dosage strengths will be 20, 30, or 40 mg. Tablets will be supplied in HDPE, child-resistant, tamper-evident bottles.
name: Afatinib
other_name: N-[4-[(3-Chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4(dimethylamino)-2-butenamide
type: Drug
description: Induction chemotherapy: 175 mg/m2 day 1 every 21 days for 2 cycles (IV infusion as per institutional standard).
name: Paclitaxel
other_name: NSC 673089
TaxolR
type: Drug
description: Carboplatin is available as a sterile lyophilized powder in single-dose vials containing 50 mg, 150 mg, or 450 mg of carboplatin. Each vial contains equal parts by weight of carboplatin and mannitol. Commercial supplies of carboplatin will be used in this trial.
name: Carboplatin
other_name: cis-Diammine(1,1-cyclobutanedicarboxylato)platinum(II)
type: Drug
description: Concurrent chemotherapy: 40 mg/m2 once weekly for 7 cycles (IV infusion as per institutional standard).
name: Cisplatin
other_name: CDDP
Cis-diaminedichloroplatinum Cis-diaminedichloroplatinum (II)
DACP
DDP
NSC 119875 R R
Platinol
Platinol-AQ
cis-platinum
diaminedichloroplatinum
platinum
type: Drug
description: Standard Fractionation 70 Gy /35 fractions at 2 Gy/day for 5 days per week.
name: Intensity Modulated Radiation Therapy
other_name: IMRT
type: Radiation
Study arms:
design_group_description: Eligible patients will begin with a 14-day lead-in period with afatinib alone. This will be followed immediately by 2 cycles of induction chemotherapy (IC) with carboplatin AUC 6 IV Day 1, paclitaxel 175mg/m2 IV Day 1, and oral afatinib as a continuous daily dosing. Each cycle is repeated every 21 days. After completion of 2 cycles of IC, patients will be assessed for response by CT/MRI and clinical exam. After the induction, all patients will receive Intensity Modulated Radiation Therapy (IMRT) with weekly cisplatin 40mg/m2 IV. Chemoradiotherapy (CRT) will begin 2-3 weeks after the completion of the second cycle of IC. The patients will be evaluated with a MRI or CT, and FDG PET approximately 12 weeks after completion of CRT.
design_group_title: Study Arm
design_group_type: Experimental
Sponsor: The Sidney Kimmel Comprehensive Cancer Center
Collaborators: The Vanderbilt-Ingram Cancer Center
National Comprehensive Cancer Network, Inc.
Drug name mappings:
name: 马来酸阿法替尼
lang: CN
name: Afatinib Dimaleate
lang: EN
name: アファチニブマレイン酸塩
lang: JP
name: 卡铂
lang: CN
name: Carboplatin
lang: EN
name: カルボプラチン
lang: JP
name: 紫杉醇
lang: CN
name: Paclitaxel
lang: EN
name: パクリタキセル
lang: JP
name: 顺铂
lang: CN
name: Cisplatin
lang: EN
name: シスプラチン
lang: JP