Induction Modified TPF Followed by Concurrent Chemoradiotherapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy and safety of induction mTPF chemotherapy followed by concurrent chemoradiotherapy for locally advanced squamous cell carcinoma of the head and neck cancer

Detailed Description
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The prognosis of patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) is poor, therefore continuous research effort is being made in order to improve treatment efficacy. Standard treatment consists of concurrent chemoradiotherapy (CCRT) with cisplatin. In spite of many clinical trials and meta-analyses, the improvement of patient outcomes with the use of induction chemotherapy (IC) hasn´t been clearly demonstrated, partially due to the high toxicity of the standard TPF (docetaxel+cisplatin+fluorouracil) regimen used most frequently in this setting. Therefore, the aim of this study is to evaluate the outcomes of patients with LASCCHN treated with a less toxic induction mTPF regimen followed by CCRT. The study will include patients with LASCCHN who - by the decision of the multidisciplinary team - have been assigned treatment with IC followed by CCRT. After being informed about the study objectives and potential risks, all patients giving written informed consent and meeting all the eligibility criteria will start the treatment. According to the study protocol, participants will receive 4 cycles of induction mTPF regimen repeated every 2 weeks followed by computed tomography (CT) response evaluation. 3-6 weeks after having completed the last cycle of mTPF, patients without disease progression will start CCRT with 2 cycles of cisplatin every 3 weeks. Twelve weeks after radiotherapy termination, a PET-CT scan will be performed in order to evaluate the treatment outcome.

Official Title
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A Phase II Study of Efficacy and Safety of Induction Modified TPF (mTPF) Followed by Concurrent Chemoradiotherapy (CCRT) in Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LASCCHN)

Conditions
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Locally Advanced Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: modified TPF
* Other: Quality of life assessment (QoL)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN): oral cavity, oropharynx, larynx and hypopharynx stage cT4 and/or cN2-N3, with no distant metastases (M0). Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2 initial clinical staging evaluated in: CT scan or MRI of the neck and CT scan of the chest or FDG18 PET TC Exclusion Criteria: patients with p16 positive oropharyngeal carcinoma cT0-T3 N2 M0 (stage II), unless extranodal tumor extension contraindications for cisplatin administration: renal insufficiency (eGFR < 55ml/min), hearing loss, peripheral neuropathy dysphagia G>2 with no percutaneous gastrostomy the presence of distant metastasis (M1)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: induction mTPF<br>4 CYCLES OF INDUCTION mTPF: Docetaxel 40 mg/m2 iv day 1, Cisplatin 40 mg/m2 iv day 1, Leucovorin 400 mg/m2 iv followed by Fluorouracil (5FU) bolus 400 mg/m2 iv day 1, 5FU 1000 mg/m2 iv day 1-2, q2w. Primary neutropenic fever prophylaxis with GCSFs x 3 days CONCURRENT CHEMORADIOTHERAPY WITH 2 CYCLES OF CISPLATIN 100mg/m2 iv q3w | Drug: modified TPF<br>* modified TPF: modified docetaxel-cisplatin-fluorouracil followed by concurrent chemoradiotherapy<br>Other: Quality of life assessment (QoL)<br>* Quality of life assessment with questionnaires: EORTC QLQ-C30 and QLQ H&N-35<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate (ORR) | percentage of partial and complete response rates (RR) | 12 weeks after radiotherapy termination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24 month progression free survival (PFS) | PFS at 24 months after treatment initiation | 2 years | 
| 24 month overall survival (OS) | OS at 24 months after treatment initiation | 2 years | 
| toxicity of induction mTPF | percentages of patients with adverse effects during induction mTPF | up to 10 weeks | 
| toxicity of concurrent chemoradiotherapy (CCRT) | percentages of patients with adverse effects during CCRT | through study completion, an average of 2 years | 
| EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) | measurement of patients' physical, psychological and social functions | 9 months | 
| EORTC Head and Neck Cancer specific module (EORTC QLQ-H&N35) | assessment the HR-QoL specific for head-and-neck cancer patients | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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head and neck cancer, induction chemotherapy, modified TPF, concurrent chemoradiotherapy