Phase I-/II-study of Hyperfractionated-Accelerated Radiation Therapy plus Cetuximab plus Cisplatin chemotherapy in locally advanced inoperable squamous cell cancers of head and neck

ISRCTN	ISRCTN47339346
DOI	https://doi.org/10.1186/ISRCTN47339346
Secondary identifying numbers	Final 01/15.02.05

Submission date: 13/09/2005
Registration date: 22/08/2006
Last edited: 01/06/2009

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Kuhnt Thomas
Scientific

Universitätsklinikum Rostock AöR
Zentrum für Radiologie
Klinik und Poliklinik für Strahlentherapie
Südring 75
Rostock
18059
Germany

Study information

Study design	Open-label, non-randomised phase I/II study
Primary study design	Interventional
Secondary study design	Non randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title
Study acronym	HART-CIS-CET
Study objectives	An improvement of loco-regional disease control by addition of cetuximab (CET) to hyperfractionated-accelerated radiation therapy (HART) and cisplatin (CIS) is expected. As of 01/06/2009 this record has been updated. All updates can be found in the relevant fields under the above update date. At this time, the anticipated end date of this trial was extended from 31/12/2007 to 31/12/2012, and the initial target number of participants was 67.
Ethics approval(s)	Ethics commission of the Medical Faculty of the Martin-Luther-University Halle-Wittenberg gave approval on the 10th June 2005.
Health condition(s) or problem(s) studied	Squamous cell carcinoma (SCC)
Intervention	Phase I: 1. HART: 30/2 Gy once daily, then twice daily 1/4 Gy to a total dose of 70/6 Gy 2. Chemotherapy: cisplatin - escalating doses (20, 30, 35, 40 mg/sqm), once weekly (typically on Monday), week one to six intravenous (iv) over a one hour infusion on days 1, 8, 15, 22, 29, 36 3. Antibody: cetuximab - loading dose 400 mg/sqm iv over a 120-min infusion on day 7 followed by subsequent weekly doses of 250 mg/sqm weeks one to six iv over a one hour infusion on days 1, 8, 15, 22, 29, 36 Phase II: 1. HART: see phase I 2. Chemotherapy: cisplatin at the recommended dose level defined in phase I 3. Antibody: see phase I
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase I/II
Drug / device / biological / vaccine name(s)	Cetuximab, cisplatin
Primary outcome measure	Phase I: Definition of maximum tolerated dose (MTD) of cisplatin in HART-CIS-CET Phase II: Determination of the two year progression-free survival (PFS)
Secondary outcome measures	Phase I: 1. Evaluation of toxicity (according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0) 2. Determination of objective tumour response rate (ORR) (according to Response Evaluation Criteria In Solid Tumors [RECIST]) 3. Determination of one, two and five year PFS, loco-regional progression-free survival (LPFS) and overall survival (OS) Phase II: 1. Determination of one and five year-PFS 2. Determination of one, two and five year LPFS and OS 3. Determination of ORR (according to RECIST) 4. Evaluation of toxicity (according to CTCAE version 3.0)
Overall study start date	10/06/2005
Completion date	31/12/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Added 01/06/2009: Phase I: 18, Phase II: 74
Key inclusion criteria	1. Patients with histologically confirmed unresectable squamous cell carcinoma (SCC) of the oral cavity (no lip), oropharynx, hypopharynx or larynx (stage III/IVa or b) 2. Unidimensionally measurable lesion 3. Signed informed consent 4. Karnofsky Performance Status more than or equal to 70% 5. Aged between 18 and 70 years 6. Curative treatment intent 7. Negative serum or urine pregnancy test (women of childbearing potential) 8. Adequate bone marrow, hepatic and renal function All patients should have a dental examination and appropriate, dental therapy if required prior to the beginning of radiotherapy. A percutaneous gastrostomy (PEG) is required.
Key exclusion criteria	1. Unknown primary cancer, nasopharynx cancer or salivary gland cancer 2. Metastatic disease 3. Another cancer within five years of study entry 4. Serious concomitant disease or medical condition 5. Pregnancy or lactation 6. Women of child-bearing potential with unclear contraception 7. Previous treatment with chemotherapy, radiotherapy or surgery in head and neck 8. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study screening 9. Life expectancy less than three months 10. Contraindications to receive cisplatin or cetuximab 11. Previous exposure to monoclonal antibodies and/or epidermal growth factor receptor (EGFR)-targeted therapy 12. Social situations that limit the compliance with study requirements
Date of first enrolment	10/06/2005
Date of final enrolment	31/12/2012

Locations

Countries of recruitment

Germany
Netherlands

Study participating centre

Universitätsklinikum Rostock AöR

Rostock
18059
Germany

Sponsor information

Martin-Luther-University Halle-Wittenberg (Germany)
University/education

Medical Faculty
Magdeburger Strasse 27
Halle/Saale
06120
Germany

Website	http://www.kks-halle.de
"ROR"	https://ror.org/05gqaka33

Funders

Funder type

Industry

Merck Pharma GmbH Darmstadt (Germany)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan