Squamous Cell Carcinoma of the Neck Clinical Trial
— ICRATOfficial title:
Randomized Phase II Study of Two Different Regimens of TPF Induction Chemotherapy Regimen Followed by Radiation Therapy Plus Cetuximab (TPF-CET-HART) vs. HART and Cis-platinum, 5-FU (PF-HART) in Patients With Locally Advanced Unresectable Squamous Cell Carcinomas of the Head and Neck
| Verified date | January 2019 |
| Source | Charite University, Berlin, Germany |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This is an open-label, randomized, Phase II-study to evaluate the efficacy of a standard-TPF
induction chemotherapy (IC) and an alternative TPF induction chemotherapy followed by
radio-antibody-therapy, in patients with unresectable LA-SCC of the HN region
(oro-hypopharynx carcinoma, cancer of the oral cavity).
The primary objective of the study is to assess the feasibility of an experimental
'fractionated' TPF regimen compared to a current standard TPF regimen.
Composite endpoint of compliance and feasibility in terms of
- response (RECIST1.1) and
- hematological acute toxicity (CTCAE v.4.02)
- on time application of RAT following an experimental or standard TPF IC.
Secondary endpoints are
- Treatment intensity achieved
- Toxicity (according to CTCAE v.4.02)
- Response rates after completion of induction chemotherapy and after completion of entire
protocol treatment (RECIST1.1)
- Survival (progression-free, metastasis-free, recurrence-free, overall) 1 year after
randomisation
- Quality of life according to EORTC QoL C30 & HN35
The study will be conducted at 5-6 investigational sites in Germany recruiting 90 patients in
total. Eligible patients will have a diagnosis of histologically confirmed SSC of the HN.
Patients will receive one of 2 different regimens of TPF IC followed by cetuximab together
with radiotherapy (RAT) or a standard radiochemotherapy(RCT) regimen.
| Status | Completed |
| Enrollment | 94 |
| Est. completion date | August 2015 |
| Est. primary completion date | April 2015 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Histologically proven unresectable SCC of the oral cavity, oropharynx and hypopharynx (stage IVA & IVB) - Written and signed informed consent - Karnofsky PS > 70 % - Age = 18 years - Curative treatment intent - Adequate bone marrow, hepatic and renal functions as evidenced by the following: Hematology (Bone marrow): - Neutrophils > 2.0 109/L - Platelets > 100 x 109/L - Hemoglobin > 10 g/dL Hepatic function: - Total serum bilirubin < 1 time the UNL of the participating center - ASAT (SGOT) and ALAT (SGPT) < 2.5 x UNL - Alkaline phosphatase < 5 x UNL Renal function : - serum creatinine (SC) < 120 µmol/L (1.4 mg/dl); - if values are > 120 µmol/L, the creatinine clearance should be > 60 ml/min (actual or calculated by the Cockcroft-Gault method as follows : weight (kg) x (140 - age) --------------------------------- K x serum creatinine serum creatinine in mg/dL: K = 72 in man K = 85 in woman serum creatinine in µmol/L: K = 0.814 in man K = 0.96 in woman • If of childbearing potential, willingness to use effective contraceptive method for the study duration and 2 months post-dosing. All patients require: - dental examination and appropriate dental preservation if needed 1 week prior to the beginning of radiotherapy, - gastric feeding tube and Portal-catheter. Exclusion Criteria: - Other neoplasia within the past 5 years with the exception of a controlled skin cancer or "in situ" cervix cancer - Unknown primary (CUP), nasopharynx, laryngeal or salivary gland cancer - Distant metastatic disease (M1) - Serious co-morbidity, e.g. arteriosclerosis with apoplexy, recent myocardial infarction, high-grade carotid stenoses, unstable cardiac disease despite treatment, congestive heart failure NYHA grade 3 and 4, insulin-dependent diabetes mellitus, uncontrolled hypertension, liver cirrhosis (Quick < 75%, total protein <3.0 g/dl, bilirubin >2mg/ml) or kidney insufficiency (creatinine >1.4 mg/ml, the creatinine clearance should be > 60 ml/min) - patients with ASAT or ALAT > 2.5 UNL associated with alkaline phosphatase > 5 UNL are not eligible for the study - Known HIV-infection - Pregnancy or lactation - Women of child-bearing potential with unclear contraception - Previous treatment of the disease with chemotherapy, radiotherapy, EGFR-targeting agents or surgery exceeding biopsy in head and neck - Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study screening - Social situations that limit compliance with study requirements - Deficient dental preservation status or not accomplished wound healing - Legal incapacity - Prior accommodation in an institution under officially or judicially orders (§ 40 1 p. 3 No. 4 AMG) - Symptomatic peripheral neuropathy National Cancer Institute-Common Toxicity Criteria (NCI-CTC) grade 2 and/or ototoxicity grade 2, except if due to trauma or mechanical impairment due to tumor mass - Known allergic/hypersensitivity reaction to any of the components of the treatment |
| Country | Name | City | State |
|---|---|---|---|
| Germany | Charité Universitaetsmedizin Berlin, CVK, CBF | Berlin | |
| Germany | University Medical Center Hamburg - Eppendorf | Hamburg | |
| Germany | Medizinische Hochschule Hannover | Hannover | |
| Germany | Universitätsklinikum Gießen und Marburg | Marburg | |
| Germany | Universitätsklinikum Regensburg | Regensburg |
| Lead Sponsor | Collaborator |
|---|---|
| Charite University, Berlin, Germany |
Germany,
Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 random — View Citation
Haddad R, Colevas AD, Tishler R, Busse P, Goguen L, Sullivan C, Norris CM, Lake-Willcutt B, Case MA, Costello R, Posner M. Docetaxel, cisplatin, and 5-fluorouracil-based induction chemotherapy in patients with locally advanced squamous cell carcinoma of t — View Citation
Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, — View Citation
Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL; EORTC 24971/TAX 323 Study Group. Cisplatin, fl — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Feasibility of an experimental 'fractionated' TPF regimen compared to a current standard TPF regimen. | acute hematological toxicity | August 2010- December 2012 | |
| Secondary | Survival and late morbidity | All adequate items illustrating acute toxicity and late morbidity, in particular by hematological measures until one year after treatment (according to NCI-CTCAE v.4.02) Survival (progression-free, metastases-free, recurrence-free, Overall survival) after 1 year Response rates after TPF IC (RECIST1.1) Response rates after completion of multimodal treatment (see follow-up for scheduling RECIST1.1) Efficacy in relation to HPV status (p16 IHC) Quality of life according to EORTC QLC-30 & HN35 | 1 year |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Active, not recruiting |
NCT03323463 -
Major De-escalation to 30 Gy for Select Human Papillomavirus Associated Oropharyngeal Carcinoma
|
Phase 2 |