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Randomised Phase II, Cetuximab in Combination With 5FU and Cisplatin or Carboplatin Versus Cetuximab in Combination With Paclitaxel and Carboplatin for Treatment of Patients With Metastatic Squamous Cell Carcinoma of the Head and Neck (CETMET)

Primary Purpose

Squamous Cell Carcinoma of the Head and Neck

Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Cetuximab
Sponsored by
Karolinska University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Squamous Cell Carcinoma of the Head and Neck

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria

  • >18 years
  • Histologically or cytologically confirmed SCCHN, relapsed and/or metastatic
  • Patient must have a life expectancy of at least 3 months allowing adequate follow-up toxicity evaluation.
  • Clinical examination
  • 1 unidimensional lesion according to RECIST 1.1.
  • PS WHO 0-1 at study entry
  • Adequate hematological function defined as WBC ≥3 x 109/litre and platelets ≥100 x 109/litre, ANC > 1.5 x 109/litre and Hb > 100 g/L
  • Adequate liver function; bilirubin < 1.5 x UNL, ALAT or ASAT<3.0 UNL, alkaline phosphates < 2.5 UNL.
  • Creatinine clearance > 50mL/min
  • Written informed consent must be obtained according to the local Ethics committee.

Exclusion Criteria:

  • > 75 years
  • Nasopharyngeal cancer and cancer of the paranasal sinuses
  • Inability to follow the treatment and evaluation schedule
  • Any other condition or therapy which in the investigator's opinion may pose a risk to the patient or interfere with the study objectives
  • Pregnant or nursing females or male or female of child-bearing potential not using adequate methods of birth-control
  • Patients with active infections or any other serious underlying medical condition, which would impair the ability of the patients to receive the protocol treatment
  • Known hypersensitivity to any of the components of the treatment
  • Legal incapacity
  • Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the last 12 months.
  • Patients with clinically relevant neuropathy
  • Previously treated for relapsed or metastatic SCCHN except radiotherapy for previously treated relapse if terminated > 3 months before start of treatment.
  • Previously treated with cetuximab, cisplatin/carboplatin, 5-FU or taxanes for locally advanced SCCHN within 3 months before study entry.

Sites / Locations

  • Lena SpechtRecruiting
  • Hedda HaugenRecruiting
  • Karolinska UniversityhospitalRecruiting
  • Karin SöderströmRecruiting
  • Akademiska Universityhospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm A: cetuximab with 5FU and carboplatin or cisplatin

Arm B: cetuximab paclitaxel and carboplatin

Arm Description

Arm A:Day 1 Cetuximab 400 mg/m2 iv 120 minutes Day 8 and 15 Cetuximab 250 mg/m2 iv 60 minutes Day 1 Cisplatin 100mg/m2 or Carboplatin AUC 5 day 1-4 5-Fluorouracil 1000 mg/m2 iv 24 h maintenance treatment thereafter with cetuximab 500 mg/m2 every second week until PD or toxicity

Arm B day 1 Cetuximab 400 mg/m2 iv 120 minutes Day 8 and 15 Cetuximab 250 mg/m2 iv 60 minutes day 1 Paclitaxel 175 mg/m2 day 1 Carboplatin AUC 5 treatment for 6 cycles thereafter maintenance treatment day 1 Cetuximab 500 mg/m2 every second week treatment until progress or unacceptable toxicity

Outcomes

Primary Outcome Measures

Progression free survival
To investigate in patients with relapsed or metastatic squamous cell carcinoma of the head and neck whether progression free survival (PFS) in the arm with cetuximab, paclitaxel and carboplatin based chemotherapy is not markedly worse than PFS in the arm with cetuximab and 5-FU, cisplatin or carboplatin based chemotherapy.

Secondary Outcome Measures

Best overall response
To compare in patients with relapsed or metastatic squamous cell carcinoma of the head and neck the following study variables between both treatment arms: Best overall response Duration of response Time to treatment failure Overall survival Safety

Full Information

First Posted
April 10, 2013
Last Updated
May 19, 2013
Sponsor
Karolinska University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01830556
Brief Title
Randomised Phase II, Cetuximab in Combination With 5FU and Cisplatin or Carboplatin Versus Cetuximab in Combination With Paclitaxel and Carboplatin for Treatment of Patients With Metastatic Squamous Cell Carcinoma of the Head and Neck
Acronym
CETMET
Official Title
Cetuximab 5-FU and Cisplatin or Carboplatin Versus Cetuximab With Paclitaxel and Carboplatin Treatment of Metastatic Squamous Cell Carcinoma of Head and Neck
Study Type
Interventional

2. Study Status

Record Verification Date
May 2013
Overall Recruitment Status
Unknown status
Study Start Date
November 2011 (undefined)
Primary Completion Date
November 2013 (Anticipated)
Study Completion Date
November 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Karolinska University Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Primary To investigate in patients with relapsed or metastatic squamous cell carcinoma of the head and neck whether progression free survival (PFS) in the arm with cetuximab, paclitaxel and carboplatin based chemotherapy is not markedly worse than PFS in the arm with cetuximab and 5-FU, cisplatin or carboplatin based chemotherapy. Secondary To compare in patients with relapsed or metastatic squamous cell carcinoma of the head and neck the following study variables between both treatment arms: Best overall response Duration of response Time to treatment failure Overall survival Safety
Detailed Description
Recurrent and/or metastatic SCCHN patients are, by definition patients with recurrent disease and/or with newly diagnosed distant metastases, although this group of patients has a very heterogeneous disease characteristic, they share a dismal prognosis that has changed little in the past 30 years. The median survival time remains around 6-8 months with a poor quality of life. Patients with resectable locoregionally recurrent SCCHN may benefit from surgery. Patients with recurrent SCCHN who are not suitable for curative salvage surgery or re-irradiation, and patients who have distant metastases, usually receive CT (Cohen EE et al.) A number of compounds demonstrate single-agent activity in recurrent and/or metastatic disease including cisplatin, carboplatin, methotrexate, 5-FU, bleomycin and the taxanes ( Scantz SP et al). Cisplatin is one of the most active agents identified for head and neck cancer, with carboplatin providing an alternative for patients unable to tolerate cisplatin. While carboplatin is associated with lower response rates than cisplatin, there appears to be no difference between the agents in terms of survival Cetuximab is a targeted therapeutic agent, a chimeric IgG1 monoclonal antibody that specifically binds to the EGFR with high affinity, internalising the receptor and preventing the ligands EGF and TGF-alfa from interacting with the receptors and thus effectively blocking ligand-induced EGFR phosphorylation. In addition, cetuximab has been found to potentiate the effects of chemotherapy and radiotherapy in experimental systems. The dose of cetuximab has been found to be generally safe and effective in several studies in major tumor types expressing the EGFR. These included colorectal cancer, squamous cell carcinoma of the head and neck and non-small cell lung cancer, with cetuximab given either in combination studies with chemotherapy and radiotherapy or as monotherapy. The main side effects of cetuximab monotherapy are hypersensitivity- and acne-like skin reactions.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Carcinoma of the Head and Neck

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Arm A: cetuximab with 5FU and carboplatin or cisplatin
Arm Type
Active Comparator
Arm Description
Arm A:Day 1 Cetuximab 400 mg/m2 iv 120 minutes Day 8 and 15 Cetuximab 250 mg/m2 iv 60 minutes Day 1 Cisplatin 100mg/m2 or Carboplatin AUC 5 day 1-4 5-Fluorouracil 1000 mg/m2 iv 24 h maintenance treatment thereafter with cetuximab 500 mg/m2 every second week until PD or toxicity
Arm Title
Arm B: cetuximab paclitaxel and carboplatin
Arm Type
Experimental
Arm Description
Arm B day 1 Cetuximab 400 mg/m2 iv 120 minutes Day 8 and 15 Cetuximab 250 mg/m2 iv 60 minutes day 1 Paclitaxel 175 mg/m2 day 1 Carboplatin AUC 5 treatment for 6 cycles thereafter maintenance treatment day 1 Cetuximab 500 mg/m2 every second week treatment until progress or unacceptable toxicity
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
Group A:Day 1 Cetuximab 400 mg/m2 iv 120 minutes Day 8 and 15 Cetuximab 250 mg/m2 iv 60 minutes Day 1 Cisplatin 100mg/m2 or Carboplatin AUC 5 day 1-4 5-Fluorouracil 1000 mg/m2 iv 24 h Group B day 1 Cetuximab 400 mg/m2 iv 120 minutes Day 8 and 15 Cetuximab 250 mg/m2 iv 60 minutes day 1 Paclitaxel 175 mg/m2 day 1 Carboplatin AUC 5 treatment for 6 cycles thereafter day 1 Cetuximab 500 mg/m2 every second week treatment until progress or unacceptable toxicity
Primary Outcome Measure Information:
Title
Progression free survival
Description
To investigate in patients with relapsed or metastatic squamous cell carcinoma of the head and neck whether progression free survival (PFS) in the arm with cetuximab, paclitaxel and carboplatin based chemotherapy is not markedly worse than PFS in the arm with cetuximab and 5-FU, cisplatin or carboplatin based chemotherapy.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Best overall response
Description
To compare in patients with relapsed or metastatic squamous cell carcinoma of the head and neck the following study variables between both treatment arms: Best overall response Duration of response Time to treatment failure Overall survival Safety
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria >18 years Histologically or cytologically confirmed SCCHN, relapsed and/or metastatic Patient must have a life expectancy of at least 3 months allowing adequate follow-up toxicity evaluation. Clinical examination 1 unidimensional lesion according to RECIST 1.1. PS WHO 0-1 at study entry Adequate hematological function defined as WBC ≥3 x 109/litre and platelets ≥100 x 109/litre, ANC > 1.5 x 109/litre and Hb > 100 g/L Adequate liver function; bilirubin < 1.5 x UNL, ALAT or ASAT<3.0 UNL, alkaline phosphates < 2.5 UNL. Creatinine clearance > 50mL/min Written informed consent must be obtained according to the local Ethics committee. Exclusion Criteria: > 75 years Nasopharyngeal cancer and cancer of the paranasal sinuses Inability to follow the treatment and evaluation schedule Any other condition or therapy which in the investigator's opinion may pose a risk to the patient or interfere with the study objectives Pregnant or nursing females or male or female of child-bearing potential not using adequate methods of birth-control Patients with active infections or any other serious underlying medical condition, which would impair the ability of the patients to receive the protocol treatment Known hypersensitivity to any of the components of the treatment Legal incapacity Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the last 12 months. Patients with clinically relevant neuropathy Previously treated for relapsed or metastatic SCCHN except radiotherapy for previously treated relapse if terminated > 3 months before start of treatment. Previously treated with cetuximab, cisplatin/carboplatin, 5-FU or taxanes for locally advanced SCCHN within 3 months before study entry.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Signe Friesland, MD Phd
Organizational Affiliation
Karolinska Universityhospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lena Specht
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lena Specht, MD DMSc Professor
Email
lena.specht@rh.regionh.dk
First Name & Middle Initial & Last Name & Degree
Lena Specht, MD DMSc Professor
Facility Name
Hedda Haugen
City
Göteborg
ZIP/Postal Code
413 45
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hedda Haugen, MD
Email
hedda.haugen@vgregion.se
First Name & Middle Initial & Last Name & Degree
Hedda Haugen, MD
Facility Name
Karolinska Universityhospital
City
Stockholm
ZIP/Postal Code
17176
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Teresa herlestam-calero-moreno, MD
Email
maria.herlestam-calero-moreno@karolinska.se
First Name & Middle Initial & Last Name & Degree
Teresa maria.herlestam-calero-moreno, MD
Facility Name
Karin Söderström
City
Umeå
ZIP/Postal Code
90189
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karin Söderström, D
Email
karin.soderstrom@onkologi.umu.se
First Name & Middle Initial & Last Name & Degree
Karin Söderström, MD
Facility Name
Akademiska Universityhospital
City
Uppsala
ZIP/Postal Code
751 85
Country
Sweden
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Silvia Johansson, MD
Email
silvia.johansson@onkologi.uu.se
First Name & Middle Initial & Last Name & Degree
Silvia Johansson, MD

12. IPD Sharing Statement

Learn more about this trial

Randomised Phase II, Cetuximab in Combination With 5FU and Cisplatin or Carboplatin Versus Cetuximab in Combination With Paclitaxel and Carboplatin for Treatment of Patients With Metastatic Squamous Cell Carcinoma of the Head and Neck

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