InductionChemo-Radio-Antibody-Treatment

• Status: Completed
• Trial end date: 2015-08-01
• Target enrollment: 0
• Participant gender: 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 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Charite University, Berlin, Germany
• Treatments: 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