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

NCT ID: NCT01830556

Last Updated: 2013-05-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2015-11-30

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.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Study Design

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

Study Groups

Arm A: cetuximab with 5FU and carboplatin or cisplatin

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

Group Type: ACTIVE_COMPARATOR

Cetuximab

Intervention Type: DRUG

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

Arm B: cetuximab paclitaxel and carboplatin

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

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: DRUG

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

Interventions

Cetuximab

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

Intervention Type: DRUG

Other Intervention Names

Erbitux

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karolinska University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Signe Friesland

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Signe Friesland, MD Phd

Role: PRINCIPAL_INVESTIGATOR

Karolinska Universityhospital

Locations

Lena Specht

Copenhagen, , Denmark

Site Status: RECRUITING

Karolinska Universityhospital

Stockholm, Stockholm County, Sweden

Site Status: RECRUITING

Hedda Haugen

Gothenburg, , Sweden

Site Status: RECRUITING

Karin Söderström

Umeå, , Sweden

Site Status: RECRUITING

Akademiska Universityhospital

Uppsala, , Sweden

Site Status: NOT_YET_RECRUITING

Countries

Denmark; Sweden

Facility Contacts

Lena Specht, MD DMSc Professor

Role: primary

lena.specht@rh.regionh.dk

Teresa herlestam-calero-moreno, MD

Role: primary

maria.herlestam-calero-moreno@karolinska.se

Hedda Haugen, MD

Role: primary

hedda.haugen@vgregion.se

Karin Söderström, D

Role: primary

karin.soderstrom@onkologi.umu.se

Silvia Johansson, MD

Role: primary

silvia.johansson@onkologi.uu.se

Other Identifiers

CETMET study

Identifier Type: -

Identifier Source: org_study_id