Overview
InductionChemo-Radio-Antibody-Treatment
Status:
Completed
Completed
Trial end date:
2015-08-01
2015-08-01
Target enrollment:
0
0
Participant gender:
All
All
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.Phase:
Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Charite University, Berlin, GermanyTreatments:
Antibodies
Cetuximab
Cisplatin
Docetaxel
Immunoglobulins
Criteria
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