Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer

NCT01216020 | Terminated Phase 2 DMC

• 1 other identifier: eudract 2010-021552-26
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 7

Brief Summary

BACKGROUND: Concomitant radiotherapy and cisplatin (CDDP) based chemotherapy is the standard treatment for LA-NHSCC. This combined modality treatment is linked with considerable acute local and systemic toxicity.EGFR is overexpressed in 90-100% of the HNSCC cases and is considered an unfavourable prognostic marker. EGFR costitutive activation is linked with HNSCC pathogenesis. Cetuximab is a monoclonal anti-EGFR antibody blocking the activation of the receptor and signal transduction. Cetuximab combined with radiotherapy is superior to radiotherapy only in the treatment of LA-HNSCC and is characterized by an acceptable toxicity profile. RATIONALE: A direct comparison between concomitant chemoradiotherapy with Cisplatin and the concomitant treatment with radiotherapy associated to cetuximab does not exist. STUDY DESIGN: Arm A: Radical radiotherapy (doses and volumes) concomitant with chemotherapy with Cisplatin (40 mg/mq/week) Arm B: Radical radiotherapy (doses and volumes) concomitant with therapy with the monoclonal antibody Cetuximab (400 mg/m2 \["loading dose"\] and subsequently 250 mg /m2/week)

Conditions

Head and Neck Neoplasms; Laryngeal Neoplasms; Mouth Neoplasms; Pharyngeal Neoplasms

Keywords

Head and Neck Cancer; Radiotherapy; Cetuximab; Cisplatin

Outcome Measures

Primary Outcomes (1)

• Compliance

  Evaluation and comparison of the compliance of the two treatments arms

  weekly during treatment

Secondary Outcomes (5)

• event free survival

  bimonthly for two years, every 6 months thereafter

• acute toxicity

  Weekly during treatment.

• Local control

  bimonthly for two years after treatment, every six months thereafter

• cause specific survival

  bimonthly after treatment for two years, then every 6 months

• overall survival

  bimonthly after treatment for two years, then every 6 months

Study Arms (2)

cetuximab plus radiotherapy

EXPERIMENTAL

Cetuximab given one week before radiotherapy (loading dose, 400 mg/m2) plus weekly (250 mg/m2), concomitant with radiotherapy (7O Gy on clinically involved sites).

Drug: cetuximab

cisplatin plus radiotherapy

ACTIVE COMPARATOR

CDDP 40 mg/mq in a single weekly 1-hour infusion concomitant to radiotherapy: (70 Gy to clinically involved sites)

Drug: cisplatin (associated to radiotherapy)

Interventions

cetuximab DRUG

* Cetuximab is given according to the standard mode of administration: "loading dose" : 400 mg/m2 one week before the start of radiotherapy (week -1), followed by a weekly dose of 250 mg/m2 during the weeks of the treatment with radiotherapy. * Radiotherapy: Doses: Clinical sites of disease (T e N) : total dose of 70 Gy given with a fractional dose of 2 Gy/day; "prophylactic" nodal volume (N) : total dose of 50 Gy given with a fractional dose of 2 Gy/day ; Treatment technique: conformal 3D. Intensity modulated radiotherapy (IMRT), also with simultaneous boost (SIB), is allowed.

Also known as: Erbitux

cetuximab plus radiotherapy

cisplatin (associated to radiotherapy) DRUG

* CDDP dose: 40 mg/mq in a single weekly 1-hour infusion preceded by adequate hydration, diuretics e antiemetic premedication. * Radiotherapy: Doses: Clinical sites of disease (T e N) : total dose of 70 Gy given with a fractional dose of 2 Gy/day; "prophylactic" nodal volume (N) : total dose of 50 Gy given with a fractional dose of 2 Gy/day ; Treatment technique: conformal 3D. Intensity modulated radiotherapy (IMRT), also with simultaneous boost (SIB), is allowed.

Also known as: Cisplatin

cisplatin plus radiotherapy

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed squamous cell carcinoma (with biopsy on the primary and / or lymph node metastases) of the oral cavity, oropharynx, hypopharynx, larynx supraglottix;
• Locally advanced disease, defined by one of the following criteria: any T, N +, M0 (excluding T1, N1), T3-4, N0, M0;
• Not cancer nasopharynx or paranasal sinuses or salivary glands;
• General conditions and associated diseases which does not allow to perform chemotherapy or radiotherapy in a radical view;
• No other surgical treatments, chemotherapy or radiotherapy for cancer of head and neck or elsewhere, except non-melanoma skin cancer or in situ cervical cancer and other solid tumors for which radical treatment has been completed \> three years prior to enrollment in the study and for which the patient has remained continuously free of disease;
• Accessibility to follow-up;
• Signing of informed consent;
• Interval between examinations of local staging and randomization, maximum 3 weeks
• Interval between randomization and initiation of treatment, maximum 2 weeks

You may not qualify if:

• Age \<18 years
• ECOG performance status \> 0-1
• Hemoglobin \<9 g / dL
• Counts of granulocytes, total \<1.5 x 10 \^ 9 / L
• Platelet count \<100 x 10 \^ 9 / L
• Bilirubin\> 1.5 times upper limit of normal (ULN)
• AST or ALT\> 3 times ULN
• Creatinine clearance \> 50 mL/min
• Mg \> 0.5 mmol/L
• Pregnancy or lactation
• Presence of allergy to study drug or to the excipients used in their formulation
• Peripheral neuropathy ≥ grade 2 (CTCAE v3.0)
• Hearing loss / tinnitus ≥ grade 3 (CTCAE v3.0)
• One of the following conditions:
• Myocardial infarction within 12 months prior to randomization

Sponsors & Collaborators

• Azienda USL 4 Prato: lead
• Università degli Studi di Brescia: collaborator

Study Sites (7)

Radiotherapy Dept., Arezzo Hospital

Arezzo, Italy

Location

Radiotherapy Dept., Brescia University and Medical Oncology Dept., Brescia Hospital

Brescia, 25100, Italy

Location

Radiotherapy Dept., Florence University

Florence, 50100, Italy

Location

Radiotherapy Dept., Genoa University

Genoa, Italy

Location

Radiotherapy Dept., Azienda USL 4 Prato

Prato, 59100, Italy

Location

Radiotherapy Dept., Siena University

Siena, Italy

Location

Radiotherapy Dept., Turin University

Torino, Italy

Location

Related Publications (1)

• Buglione M, Maddalo M, Corvo R, Pirtoli L, Paiar F, Lastrucci L, Stefanacci M, Belgioia L, Crociani M, Vecchio S, Bonomo P, Bertocci S, Borghetti P, Pasinetti N, Triggiani L, Costa L, Tonoli S, Grisanti S, Magrini SM. Subgroup Analysis According to Human Papillomavirus Status and Tumor Site of a Randomized Phase II Trial Comparing Cetuximab and Cisplatin Combined With Radiation Therapy for Locally Advanced Head and Neck Cancer. Int J Radiat Oncol Biol Phys. 2017 Mar 1;97(3):462-472. doi: 10.1016/j.ijrobp.2016.10.011. Epub 2016 Oct 20.

  PMID: 27986347 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Laryngeal Neoplasms; Mouth Neoplasms; Pharyngeal Neoplasms

Interventions

Cetuximab; Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Otorhinolaryngologic Neoplasms; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Otorhinolaryngologic Diseases; Mouth Diseases; Stomatognathic Diseases; Pharyngeal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Stefano M Magrini, Prof

  Radiotherapy Dept., Brescia Hospital and Brescia University

  STUDY CHAIR

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

Study Record Dates

• First Submitted: October 6, 2010
• First Posted: October 7, 2010
• Study Start: October 1, 2010
• Primary Completion: May 20, 2015
• Study Completion: May 20, 2015
• Last Updated: January 17, 2018

Record last verified: 2018-01

Locations

IT (7)