E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The study is a phase II study of induction chemotherapy with docetaxel plus cisplatin and fluorouracil (TPF) followed by radioimmunotherapy with Cetuximab and intensity modulated radiotherapy (IMRT) in combination with a carbon ion boost for locally advanced tumors of the oro- , hypopharynx and laynx (TPF-C-HIT-Study)
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To date no clinical trial with cetuximab in combination with IMRT plus carbon ion boost after an induction chemotherapy with TPF for locally advanced head and neck cancer has been published. Therefore the combination of the different treatment modalities is new and not investigated until now. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Endpoint Local-Regional Control (LRC) at 1 year
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E.2.2 | Secondary objectives of the trial |
Secondary Endpoints - Disease-free survival, - Progression-free survival, - Overall survival, - Acute radiation effect, - Late radiation effect, - Adverse events, - Proteomics and Genomics.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Analytical investigation: Analytical investigation of proteomics and genomics in order to predict the efficacy of the trimodal therapy blood will be collceted during therapy and follow-up to detect and correlate the levels of well known tumor- and angiogenesis markers (VEGF, TGF-Alpha, bFGF, IL8, k-ras, etc.) using Enzyme-Linked Immunosorbent Assay (ELISA). Further, platelet protein content (i.e. tumor angiogenesis growth factors and cytokines) will be analyzed using citrate blood samples and correlated with serum- and plasma- protein results. In order to perform the genomic analysis, patients’ blood samples are collected as indicated and RNA, miRNA and DNA isolation will be performed. Based on an established platform, linear RNA-amplification, labelling and hybridization on human genome wide oligo-arrays (transcriptome analysis) are planned. DNA samples are used to identify potential chromosomal aberrations or epigenetic alterations that might predict treatment response. RNA and miRNA samples are further analyzed by real time quantitative RT-PCR to confirm microarray data and to test a subset of clinical predictors identified in prior trials. |
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E.3 | Principal inclusion criteria |
I1. Signed written informed consent, 2. Age of 18 to 70 years, 3. Life expectancy of at least 6 month, 4. Ability of subject to understand character and individual consequences of clinical trial, 5. Histologically confirmed locally advanced (stage III or IV), non-metastatic squamous cell carcinoma of oro-, hypopharynx and larynx (T2-4, any N, M0), 6. Oral cavity or oro- , hypopharynx or laynx as the primary tumor site, 7. At least one uni-measurable lesion according to the RECIST criteria, 8. Karnofsky Performances Status > 70%, 9. Adequate bone marrow function: neutrophils > 1.5 x 109/L, platelets > 100 x 109/L, hemoglobin > 10.0 g/dL§, 10. Adequate liver function: Bilirubin < 1.5mg/dL, SGOT, SGPT < 3 x ULN§, GGT < 5 x ULN§, 11. Adequate renal function: GFR> 70 ml/min.§, 12. Negative serum/urine Beta-HCG test in women of childbearing potential, 13. 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 potential are those who are post-menopausal for at least 1 year or sterilized, 14. 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, 15. 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. Nonetheless, he/she may be enrolled in the study. § If in the opinion of the responsible investigator the values excluding a subject from the trial participation are transient, the flagged inclusion criteria may be re-assessed (prior to inclusion). If the control values are within the normal range the subject may be enrolled in the trial.
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E.4 | Principal exclusion criteria |
Exclusion Criteria 1. Previous systemic chemotherapy, radiotherapy or surgery for carcinoma of the head, neck and larynx, 2. Nasopharyngeal Carcinoma, 3. Prior exposure to EGFR pathway targeting therapy, 4. Evidence of distant metastases. 5. 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, 6. Participation in other interventional trial within the last 30 days§§, 7. Surgery within the last 30 days§§, 8. Known allergic/hypersensitivity reaction to any drugs scheduled for the study treatment, 9. Women: pregnant or breast-feeding, 10. Known drug abuse, 11. 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, 12. Legal incapacity or limited legal capacity, 13. 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. §§ If appropriate, the inclusion of a subject may be postponed to comply with these exclusion criteria.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint The primary endpoint of the study is the Local-Regional Control (LRC) at 1 year
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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A total of 50 subjects with locally advanced, primary untreated, primary non-metastatic, squamous cell carcinoma of the oro- and hypopharynx will be included. Each subject will receive the treatment concept described in the protocol. The overall clinical trial duration is scheduled to last for approximately 42 months. Each subject will be followed up for 18 month after his/her 1st administration of TPF, i.e. after his/her day 1.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |