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Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer (CTXMAB+RT)

Primary Purpose

Head and Neck Neoplasms, Laryngeal Neoplasms, Mouth Neoplasms

Status
Terminated
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
cetuximab
cisplatin (associated to radiotherapy)
Sponsored by
Azienda USL 4 Prato
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Neoplasms focused on measuring Head and Neck Cancer, Radiotherapy, Cetuximab, Cisplatin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Radiotherapy Dept., Arezzo Hospital
  • Radiotherapy Dept., Brescia University and Medical Oncology Dept., Brescia Hospital
  • Radiotherapy Dept., Florence University
  • Radiotherapy Dept., Genoa University
  • Radiotherapy Dept., Azienda USL 4 Prato
  • Radiotherapy Dept., Siena University
  • Radiotherapy Dept., Turin University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

cetuximab plus radiotherapy

cisplatin plus radiotherapy

Arm Description

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).

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

Outcomes

Primary Outcome Measures

Compliance
Evaluation and comparison of the compliance of the two treatments arms

Secondary Outcome Measures

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

Full Information

First Posted
October 6, 2010
Last Updated
January 16, 2018
Sponsor
Azienda USL 4 Prato
Collaborators
Università degli Studi di Brescia
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1. Study Identification

Unique Protocol Identification Number
NCT01216020
Brief Title
Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer
Acronym
CTXMAB+RT
Official Title
Multiinstitutional Open Label Randomized Phase II Study Comparing Cetuximab and Radiotherapy Versus Cisplatin and Radiotherapy as Firstline Treatment for Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LA-NHSCC)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Terminated
Why Stopped
insufficient recruitment
Study Start Date
October 2010 (undefined)
Primary Completion Date
May 20, 2015 (Actual)
Study Completion Date
May 20, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Azienda USL 4 Prato
Collaborators
Università degli Studi di Brescia

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Neoplasms, Laryngeal Neoplasms, Mouth Neoplasms, Pharyngeal Neoplasms
Keywords
Head and Neck Cancer, Radiotherapy, Cetuximab, Cisplatin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
cetuximab plus radiotherapy
Arm Type
Experimental
Arm Description
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).
Arm Title
cisplatin plus radiotherapy
Arm Type
Active Comparator
Arm Description
CDDP 40 mg/mq in a single weekly 1-hour infusion concomitant to radiotherapy: (70 Gy to clinically involved sites)
Intervention Type
Drug
Intervention Name(s)
cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
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
Intervention Name(s)
cisplatin (associated to radiotherapy)
Other Intervention Name(s)
Cisplatin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Compliance
Description
Evaluation and comparison of the compliance of the two treatments arms
Time Frame
weekly during treatment
Secondary Outcome Measure Information:
Title
event free survival
Description
Evaluation and comparison of the event free survival (both local control and distant metastases)
Time Frame
bimonthly for two years, every 6 months thereafter
Title
acute toxicity
Description
Evaluation and comparison of the grade and incidence of acute toxicity.
Time Frame
Weekly during treatment.
Title
Local control
Description
Evaluation and comparison of local control
Time Frame
bimonthly for two years after treatment, every six months thereafter
Title
cause specific survival
Description
Evualation and comparison of cause specific survival
Time Frame
bimonthly after treatment for two years, then every 6 months
Title
overall survival
Description
evaluation and comperison of overall survival
Time Frame
bimonthly after treatment for two years, then every 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stefano M Magrini, Prof
Organizational Affiliation
Radiotherapy Dept., Brescia Hospital and Brescia University
Official's Role
Study Chair
Facility Information:
Facility Name
Radiotherapy Dept., Arezzo Hospital
City
Arezzo
Country
Italy
Facility Name
Radiotherapy Dept., Brescia University and Medical Oncology Dept., Brescia Hospital
City
Brescia
ZIP/Postal Code
25100
Country
Italy
Facility Name
Radiotherapy Dept., Florence University
City
Firenze
ZIP/Postal Code
50100
Country
Italy
Facility Name
Radiotherapy Dept., Genoa University
City
Genoa
Country
Italy
Facility Name
Radiotherapy Dept., Azienda USL 4 Prato
City
Prato
ZIP/Postal Code
59100
Country
Italy
Facility Name
Radiotherapy Dept., Siena University
City
Siena
Country
Italy
Facility Name
Radiotherapy Dept., Turin University
City
Torino
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
27986347
Citation
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.
Results Reference
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Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally Advanced Head and Neck Cancer

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