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

NCT ID: NCT01216020

Last Updated: 2018-01-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2015-05-20

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)

Detailed Description

PRIMARY OBJECTIVES:

Evaluation and comparison of the compliance of the two treatments;

SECONDARY OBJECTIVES:

Evaluation and comparison of the grade and incidence of acute toxicity; Evaluation and comparison of local control; Evaluation and comparison of event free survival (both local control and distant metastases); Evaluation and comparison of cause specific and overall survival.

INCLUSION/EXCLUSION CRITERIA

• Histologically confirmed squamous cell carcinoma (biopsy obtained from the tumor and/or from its lymphnodal metastases) originating from oral cavity, oropharynx, hypopharinx, supraglottic larynx;
• Locally advanced disease, defined by one of the following criteria: every T, N+, M0 ( T1, N1 cases excluded); T3-4, N0, M0;
• Not a nasopharynx, paranasal sinuses, salivary glands tumor;
• General conditions and concomitant diseases not considered a contraindication for chemotherapy or curative radiotherapy;
• No other surgical, chemotherapeutic or radiotherapic treatments for ENT region tumors or for tumors of other anatomical sites (with the exception of non-melanoma cutaneous tumors and of the carcinoma in situ of the uterine cervix and of other solid tumors whose primary treatment has been completed more than 3 years before the accrual in this study and never relapsed since primary treatment (the patient having been since then continuously disease- free);
• Availability for follow-up;
• Signed informed consent;
• An interval of maximum 3 weeks between staging procedures for local disease and randomization
• An interval of maximum 2 weeks between randomization and the onset of the treatment

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

cetuximab plus radiotherapy

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).

Group Type: EXPERIMENTAL

cetuximab

Intervention Type: 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.

cisplatin plus radiotherapy

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

Group Type: ACTIVE_COMPARATOR

cisplatin (associated to radiotherapy)

Intervention Type: 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.

Interventions

cetuximab

• 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.

Intervention Type: DRUG

cisplatin (associated to radiotherapy)

• 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.

Intervention Type: DRUG

Other Intervention Names

Erbitux; Cisplatin

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Severe congestive heart failure
• Unstable angina
• Cardiomyopathy in act
• Ventricular arrhythmia
• uncontrolled hypertension
• Severe psychotic disorders in act
• Severe infection in act
• Any other serious illness that could interfere with the administration of the therapy provided by the protocol

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Università degli Studi di Brescia

OTHER

Sponsor Role: collaborator

Azienda USL 4 Prato

OTHER

Sponsor Role: lead

Responsible Party

STEFANO M. MAGRINI, PROF

PROF

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stefano M Magrini, Prof

Role: STUDY_CHAIR

Radiotherapy Dept., Brescia Hospital and Brescia University

Locations

Radiotherapy Dept., Arezzo Hospital

Arezzo, , Italy

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

Brescia, , Italy

Radiotherapy Dept., Florence University

Florence, , Italy

Radiotherapy Dept., Genoa University

Genoa, , Italy

Radiotherapy Dept., Azienda USL 4 Prato

Prato, , Italy

Radiotherapy Dept., Siena University

Siena, , Italy

Radiotherapy Dept., Turin University

Torino, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 27986347 (View on PubMed)

Other Identifiers

eudract 2010-021552-26

Identifier Type: -

Identifier Source: org_study_id