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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 94
- Locations
- 5
- Primary Endpoint
- Feasibility of an experimental 'fractionated' TPF regimen compared to a current standard TPF regimen.
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
TPF standard
TPF version 1 (standard)
- Induction chemotherapy:
Docetaxel 75 mg/m2 d 1 Cis-platinum 75 mg/m2 d 1 5-FU 750 mg/m2/d c.i. d 1-4 every 21 days for 3 cycles 2. Antibody therapy with:
cetuximab loading dose of 400 mg/m2 1 week prior to RTX, and 250 mg/m2 weekly x 6 concurrent to RTX 3. RTX: HART (72 Gy), IMRT or 3D-conformal techniques
Intervention: TPF induction chemotherapy (Drug)
TPF experimental
TPF version 2 (experimental)
- Induction chemotherapy:
Docetaxel 40 mg/m2 d 1+8 Cis-platinum 40 mg/m2 d 1+8 5-FU 1500 mg/m2/24h c.i. d 1+8 every 21 day for 3 cycles 2. Antibody therapy with:
cetuximab loading dose of 400 mg/m2 1 week prior to RTX, and 250 mg/m2 weekly x 6 concurrent to RTX 3. RTX: HART (72 Gy), IMRT or 3D-conformal techniques
Intervention: TPF experimental (Drug)
Standard RCT
Standard RCT:
- HART (72 Gy), IMRT or 3D-conformal techniques
- with concurrent chemotherapy: Cis-platinum 30 mg/m2 once weekly d 1, 8, 15, 22, 29, 36 5-FU 600mg/m² /24h c.i. d 1-5
Intervention: Standard Radiochemotherapy (HART) (Radiation)
Outcomes
Primary Outcomes
Feasibility of an experimental 'fractionated' TPF regimen compared to a current standard TPF regimen.
Time Frame: August 2010- December 2012
acute hematological toxicity
Secondary Outcomes
- Survival and late morbidity(1 year)
Investigators
Carmen Stromberger
Prof. Dr. Volker Budach
Charite University, Berlin, Germany