Clinical trial NCT01181401: InductionChemo-Radio-Antibody-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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of the Head
Squamous Cell Carcinoma of the Neck
Keywords: induction chemotherapy
radiotherapy
locally advanced head neck tumor
toxicity
LA SCCHN
Unresectable squamous cell cancer of the head and neck,
Stage IV (UICC)
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2010-08-13
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Feasibility of an experimental 'fractionated' TPF regimen compared to a current standard TPF regimen.
timeFrame: August 2010- December 2012
Secondary outcomes:
measure: Survival and late morbidity
timeFrame: 1 year
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Universitaetsmedizin Berlin, CVK, CBF
city: Hamburg
country: Germany
facility: University Medical Center Hamburg - Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Marburg
country: Germany
facility: Universitätsklinikum Gießen und Marburg
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
Study officials:
affiliation: Charité Universitaetsmedizin Berlin
name: Volker Budach, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL; EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1695-704. doi: 10.1056/NEJMoa071028.
citation: Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, Cmelak A, Markoe AM, Read PW, Steinbrenner L, Colevas AD, Norris CM Jr, Haddad RI; TAX 324 Study Group. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1705-15. doi: 10.1056/NEJMoa070956.
citation: Haddad R, Colevas AD, Tishler R, Busse P, Goguen L, Sullivan C, Norris CM, Lake-Willcutt B, Case MA, Costello R, Posner M. Docetaxel, cisplatin, and 5-fluorouracil-based induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck: the Dana Farber Cancer Institute experience. Cancer. 2003 Jan 15;97(2):412-8. doi: 10.1002/cncr.11063.
citation: Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010 Jan;11(1):21-8. doi: 10.1016/S1470-2045(09)70311-0. Epub 2009 Nov 10.