InductionChemo-Radio-Antibody-Treatment (ICRAT)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2010 by Charite University, Berlin, Germany.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT01181401
First received: August 12, 2010
Last updated: August 26, 2010
Last verified: August 2010
  Purpose

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.


Condition Intervention Phase
Squamous Cell Carcinoma of the Head
Squamous Cell Carcinoma of the Neck
Drug: TPF induction chemotherapy
Drug: TPF experimental
Radiation: Standard Radiochemotherapy (HART)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:
  • Feasibility of an experimental 'fractionated' TPF regimen compared to a current standard TPF regimen. [ Time Frame: August 2010- December 2012 ] [ Designated as safety issue: Yes ]
    acute hematological toxicity


Secondary Outcome Measures:
  • Survival and late morbidity [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 90
Study Start Date: August 2010
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: TPF standard

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
Drug: TPF 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 Cetuximab loading dose of 400 mg/m2 1 week prior to RTX, and 250 mg/m2 weekly x 6 concurrent to RTX
Other Names:
  • Docetaxel (Taxotere)
  • Cisplatin
  • 5-Flurouracil
  • Cetuximab (Erbitux)
Experimental: TPF experimental

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
Drug: TPF experimental
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
Other Names:
  • Docetaxel (Taxotere)
  • Cisplatin
  • 5-Flurouracil
  • Certuximab
Active Comparator: Standard RCT

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
Radiation: Standard Radiochemotherapy (HART)
Hyperfractionated accelerated radiotherapy with concurrent Cisplatin and 5-Fluorouracil chemotherapy
Other Names:
  • Cis-platinum
  • 5-FU

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01181401

Contacts
Contact: Carmen Stromberger, MD 0049 (0) 30 450 ext 657105 carmen.stromberger@charite.de
Contact: Sylvia Blass 0049 (0) 30 450 527 318 sylvia.blass@charite.de

Locations
Germany
Charité Universitaetsmedizin Berlin, CVK, CBF Recruiting
Berlin, Germany, 13353
Contact: Carmen Stromberger, MD    0049 (0) 30 450 ext 657105    carmen.stromberger@charite.de   
Sub-Investigator: Carmen Stromberger, MD         
Sub-Investigator: Jan-Dirk Raguse, MD         
Sub-Investigator: Eva-Tessina Becker, MD         
Sub-Investigator: Ulrich Keilholz, MD, PhD         
Sub-Investigator: Lutz Moser, MD         
Sub-Investigator: Heidi Olze, MD, PD         
University Medical Center Hamburg - Eppendorf Not yet recruiting
Hamburg, Germany, 20246
Contact: Rainald Knecht, MD, PhD    0049 (0) 40 / 74105 ext 2360    r.knecht@uke.de   
Sub-Investigator: Philippe Schafhausen, MD         
Sub-Investigator: Cordula Petersen, MD, PD         
Medizinische Hochschule Hannover Not yet recruiting
Hannover, Germany, 30625
Contact: Viktor Grünwald Grünwald, MD, PD    0049 (0) 511 5324077 / 9196    Gruenwald.Viktor@mh-hannover.de   
Sub-Investigator: Viktor Grünwald, MD, PD         
Universitätsklinikum Gießen und Marburg Not yet recruiting
Marburg, Germany, 35043
Contact: Rita Engenhart-Cabillic, MD, PD    0049 (0) 6421 58-66434    engenhar@med.uni-marburg.de   
Sub-Investigator: Rita Engenhart-Cabillic, MD, PD         
Universitätsklinikum Regensburg Not yet recruiting
Regensburg, Germany, 93053
Contact: Oliver Koelbel, MD, PD    0049 (0941) 944 9410    oliver.koelbl@klinik.uni-regensburg.de   
Sub-Investigator: Oliver Koelbl, MD, PD         
Sub-Investigator: Hermann Hilber, MD         
Sponsors and Collaborators
Charite University, Berlin, Germany
Investigators
Principal Investigator: Volker Budach, MD, PhD Charité Universitaetsmedizin Berlin
  More Information

Publications:

Responsible Party: Volker Budach, Principal Investigator, Charité Universitaetsmedizin Berlin
ClinicalTrials.gov Identifier: NCT01181401     History of Changes
Other Study ID Numbers: EudraCT No. 2010-019347-18
Study First Received: August 12, 2010
Last Updated: August 26, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Charite University, Berlin, Germany:
induction chemotherapy
radiotherapy
locally advanced head neck tumor
toxicity
LA SCCHN
Unresectable squamous cell cancer of the head and neck,
Stage IV (UICC)

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Antibodies
Fluorouracil
Docetaxel
Cetuximab
Cisplatin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Radiation-Sensitizing Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents

ClinicalTrials.gov processed this record on July 28, 2014