InductionChemo-Radio-Antibody-Treatment

NCT01181401 | Completed Phase 2 DMC

• 1 other identifier: EudraCT No. 2010-019347-18
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 5

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.

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)

Outcome Measures

Primary Outcomes (1)

• Feasibility of an experimental 'fractionated' TPF regimen compared to a current standard TPF regimen.

  acute hematological toxicity

  August 2010- December 2012

Secondary Outcomes (1)

• Survival and late morbidity

  1 year

Study Arms (3)

TPF standard

ACTIVE COMPARATOR

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

TPF experimental

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

Standard RCT

ACTIVE COMPARATOR

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)

Interventions

TPF induction chemotherapy DRUG

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

Also known as: Docetaxel (Taxotere), Cisplatin, 5-Flurouracil, Cetuximab (Erbitux)

TPF standard

TPF experimental DRUG

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

Also known as: Docetaxel (Taxotere), Cisplatin, 5-Flurouracil, Certuximab

TPF experimental

Standard Radiochemotherapy (HART) RADIATION

Hyperfractionated accelerated radiotherapy with concurrent Cisplatin and 5-Fluorouracil chemotherapy

Also known as: Cis-platinum, 5-FU

Standard RCT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 :

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (5)

Charité Universitaetsmedizin Berlin, CVK, CBF

Berlin, 13353, Germany

Location

University Medical Center Hamburg - Eppendorf

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinikum Gießen und Marburg

Marburg, 35043, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

Related Publications (4)

• 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.

  PMID: 17960012 RESULT

• 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.

  PMID: 17960013 RESULT

• 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.

  PMID: 12518365 RESULT

• 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.

  PMID: 19897418 RESULT

MeSH Terms

Interventions

Docetaxel; Cisplatin; Cetuximab; Fluorouracil

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Volker Budach, MD, PhD

  Charité Universitaetsmedizin Berlin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Volker Budach

Study Record Dates

• First Submitted: August 12, 2010
• First Posted: August 13, 2010
• Study Start: August 1, 2010
• Primary Completion: April 1, 2015
• Study Completion: August 1, 2015
• Last Updated: January 31, 2019

Record last verified: 2019-01

Locations

DE (5)