InductionChemo-Radio-Antibody-Treatment (ICRAT)

Charité University Medicine Berlin

Status and phase: Completed; Phase 2

Conditions: Squamous Cell Carcinoma of the Neck; Squamous Cell Carcinoma of the Head

Treatments: Drug: TPF experimental; Drug: TPF induction chemotherapy; Radiation: Standard Radiochemotherapy (HART)

Study type: Interventional

Funder types: Other

Identifiers

NCT01181401

EudraCT No. 2010-019347-18

Details and patient eligibility

About

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.

Enrollment: 94 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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94 participants in 3 patient groups

TPF standard

Active Comparator group

Description:

TPF version 1 (standard) 1. 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

Treatment:

Drug: TPF induction chemotherapy

TPF experimental

Experimental group

Description:

TPF version 2 (experimental) 1. 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

Treatment:

Drug: TPF experimental

Standard RCT

Active Comparator group

Description:

Standard RCT: 1. HART (72 Gy), IMRT or 3D-conformal techniques 2. 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

Treatment:

Radiation: Standard Radiochemotherapy (HART)