TPF Followed by Cetuximab and IMRT Plus Carbon Ion Boost for Locally Advanced Head and Neck Tumors

Study Overview
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Brief Summary
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TPF-C-HIT investigates the combination of induction chemotherapy with TPF followed by radioimmunotherapy with cetuximab and IMRT plus carbon ion boost with regard to efficacy and toxicity of the combination regimen.

Detailed Description
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TPF-C-HIT is a prospective, monocentric phase II trial efficacy, as measured by control and survival rates, as well as toxicity (acute and late effects) of the combined treatment with TPF-induction followed by radioimmunotherapy with the EGFR-antibody cetuximab and carbon ion boost in locally advanced squamous cell carcinoma of the head and neck (SCCHN). As long-term local control remains a therapeutic challenge in advanced head and neck cancer, locoregional control was chosen as the primary endpoint. Secondary endpoints are survival rates (disease-free survival, PFS, OS), acute and late radiation effects as well as adverse events. For development of prognostic markers, proteomic and genomic analyses are also included in the secondary endpoints.

Official Title
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Induction Chemotherapy With TPF Followed by Radioimmunotherapy With Cetuximab and Intensity Modulated Radiotherapy (IMRT) Plus Carbon Ion Boost for Locally Advanced Tumors of the Oro-, Hypopharynx and Larynx: TPF-C-HIT

Conditions
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Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN): Oro-, Hypopharyngeal and Laryngeal Cancer

Intervention / Treatment
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* Radiation: carbon ion boost


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent, Age of 18 to 70 years, Life expectancy of at least 6 month, Ability of subject to understand character and individual consequences of clinical trial, Histologically confirmed locally advanced (stage III or IV), non-metastatic squamous cell carcinoma of oro-, hypopharynx and larynx (T2-4, any N, M0), Oral cavity or oro- , hypopharynx or laynx as the primary tumor site, At least one uni-measurable lesion according to the RECIST criteria, Karnofsky Performances Status > 70%, Adequate bone marrow function: neutrophils > 1.5 x 109/L, platelets > 100 x 109/L, hemoglobin > 10.0 g/dL, Adequate liver function: Bilirubin < 1.5 mg/dL, SGOT, SGPT < 3 x ULN, GGT < 5 x ULN, Adequate renal function: GFR> 70 ml/min, Negative serum/urine Beta-HCG test in women of childbearing potential, Women of childbearing potential: willingness to use effective contraceptive method, defined as the concomitant use of either an intrauterine pessary (IUP) or contraceptive pill and in both cases, condoms for the treatment duration and 2 months thereafter. Women of non-childbearing potiential are those who are post-menopausal for at least 1 year or sterilized, Men of procreative potential: willingness for effective prevention of procreation, defined as a use of condoms and a use of either an intrauterine pessary (IUP) or a contraceptive pill by his partner for the treatment duration and 2 months thereafter, Subject's consent to collect blood and/or tumor tissue samples for proteomics and genomics. If a patient does not consent, no samples for proteomics and genomics will be taken. Nonetheles, he/she may be enroled in the study Exclusion Criteria: Previous systemic chemotherapy, radiotherapy or surgery for carcinoma of the head, neck and larynx, Nasopharyngeal Carcinoma, Prior exposure to EGFR pathway targeting therapy, Evidence of distant metastases. Other serious illness or medical conditions: Unstable cardiac disease despite treatment, congestive heart failure NYHA grade 3 and 4, Significant neurologic or psychiatric disorders including dementia or seizures, Active disseminated intravascular coagulation, Other serious underlying medical conditions which in the opinion of investigator could impair the ability of the patient to participate in the study, Symptomatic peripheral neuropathy Common Toxicity Criteria (CTC) grade 2 or higher, ototoxicity CTC grade 2 or higher, except if due to trauma or mechanical impairment due to tumor mass, Participation in other interventional trial within the last 30 days§§, Surgery within the last 30 days, Known allergic/hypersensitivity reaction to any drugs scheduled for the study treatment, Women: pregnant or breast-feeding, Known drug abuse, Other previous malignancy within 5 years, with exception of a history of a previous, adequately treated, basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix, Legal incapacity or limited legal capacity, Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: treatment arm<br>patients receive induction chemotherapy with TPF for a maximum of 3 cycles followed by radioimmunotherapy with cetuximab as intensity-modulated radiotherapy (IMRT) plus carbon ion boost | Radiation: carbon ion boost<br>* patients receive induction chemotherapy with TPF for a maximum of 3 cycles followed by radioimmunotherapy with cetuximab as intensity-modulated radiotherapy (IMRT) plus carbon ion boost<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local-Regional Control (LRC) | The primary endpoint of the study is the Local-Regional Control (LRC) at 1 year | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival (DFS) |  | 12 months | 
| progression-free survival (PFS) |  | 12 months | 
| overall survival (OS) |  | 12 months | 
| acute radiation effects |  | 6 weeks post completion of radiotherapy | 
| late radiation effects |  | 12 months | 
| adverse events | includes any adverse events attributable to the combined treatment not otherwise specified | 12 months | 
| proteomic and genomic analyses | proteomic and genomic analyses designed to investigate changes during therapy, therefore analyses are carried out at 6 measuring points: days 50, 64, 73, 106 of treatment; 6 weeks post completion of radioimmunotherapy; 3 months post completion of radioimmunotherapy | 6 measuring points: days 50, 64, 73, 106 of treatment; 6 weeks post completion of radioimmunotherapy; 3 months post completion of radioimmunotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCCHN, squamous cell carcinoma of the head and neck, oropharyngeal carcinoma, hypopharyngeal carcinoma, laryngeal carcinoma