Treatment Selection According to Skin Reaction to Cetuximab

This study is currently recruiting participants.
Verified December 2011 by Institute of Oncology Ljubljana
Sponsor:
Information provided by (Responsible Party):
Institute of Oncology Ljubljana
ClinicalTrials.gov Identifier:
NCT01472653
First received: October 23, 2011
Last updated: December 11, 2011
Last verified: December 2011
  Purpose

The therapy of patients with locally advanced head and neck cancer will be adjusted to the grade of skin rush as recorded after the first two cycles of Cetuximab and Cisplatin, i.e. either with radioimmunotherapy (radiotherapy and Cetuximab) or radiochemotherapy (radiotherapy and Cisplatin.


Condition Intervention Phase
Head and Neck Cancer
Drug: cisplatin
Radiation: radiotherapy
Drug: cetuximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Skin Reaction to Cetuximab as Criteria for Treatment Selection in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Phase 2 Study

Resource links provided by NLM:


Further study details as provided by Institute of Oncology Ljubljana:

Primary Outcome Measures:
  • locoregional complete response rate [ Time Frame: 12-14 weeks after therapy ] [ Designated as safety issue: No ]
    The primary objective of the study is to determine radiologically the complete response rate 12-14 weeks after therapy.


Secondary Outcome Measures:
  • feasibility (toxicity profile) of the proposed regimen [ Time Frame: participants will be followed for the duration of treatment (an expected average of 20 weeks) ] [ Designated as safety issue: Yes ]
    number of patients with adverse events graded according to the National Cancer Institute CTC v3.0 (as measure of safety and tolerability)

  • locoregional control [ Time Frame: at 2 years after thapy ] [ Designated as safety issue: No ]
    Locoregional control will be calculated from the first day of the therapy to the occurrence of the local and/or regional recurrence (whichever will occur first) or death from any cause other than distant metastasis.

  • progression-free survival [ Time Frame: 2 years after therapy ] [ Designated as safety issue: No ]
    Progression-free will be calculated from the first day of the therapy to the appearance of local or regional recurrence, distant metastases, secondary primary cancer or death from any cause.

  • overall survival [ Time Frame: 2 years after therapy ] [ Designated as safety issue: No ]
    Overall survival is defined as a time interval between the first day of therapy and death from any cause.

  • late toxicity including thyroid function [ Time Frame: up to 2 years post-therapy ] [ Designated as safety issue: Yes ]
    number of patients with adverse events graded according to the National Cancer Institute CTC v3.0 (as measure of safety and tolerability)


Estimated Enrollment: 120
Study Start Date: December 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: cisplatin
    cisplatin 30 mg/m2/week I.V. during radiotherapy
    Radiation: radiotherapy
    3-dimensional conformal radiotherapy planning and delivery, 35x2 Gy/day over 7 weeks
    Drug: cetuximab
    cetuximab 400 mg/m2 I.V. 1 week before the start of radiotherapy, cetuximab 250 mg2/week I.V. during radiotherapy
    Other Name: Erbitux
Detailed Description:

Background: According to literature, the treatment results in irradiated patients who develop intensive skin reaction after concomitant Cetuximab administration appear improved as compared to the results of standard combination of radiotherapy and Cisplatin. In other patients, no beneficial effect of Cetuximab is expected and the therapy with Cisplatin (concomitantly with irradiation) is more effective in this group.

In this proposed single-institution non-randomized phase II study on patients with locally advanced squamous cell carcinoma of the head and neck, the therapy will be adjusted to the grade of skin rush as recorded after the first two cycles of Cetuximab and Cisplatin, i.e. either with radioimmunotherapy (radiotherapy and Cetuximab) or radiochemotherapy (radiotherapy and Cisplatin).

Methods: In the patients with inoperable tumors, induction chemotherapy (Docetaxel 75 mg/m2, Cisplatin 75 mg/m2, 5-Fluorouracil 750 mg/m2 in continuous infusion days 1-5; repeated every 21 days for 4 cycles) will be administered. In the week before the first fraction of radiotherapy, all patients will receive a loading dose of Cetuximab (400 mg/m2) and combination of Cetuximab (250 mg/m2) and Cisplatin (30 mg/m2) during the first week of irradiation. After multidisciplinary assessment of the grade of skin rush, conducted at the end of the second week of irradiation, the patients will be grouped as follows: arm A - skin rush of CTCAE v3.0 grade <2 will proceed with radiochemotherapy with Cisplatin; arm B - skin rush of CTCAE v3.0 grade >=2 will proceed with radioimmunotherapy with Cetuximab.

The planned number of patients included in the study is 120 (arm A - 50, arm B - 70) and recruitment period is 3 years. The primary objective of the study is to determine radiologically the complete response rate 12-14 weeks after therapy. The secondary objectives are locoregional control, progression-free survival and overall survival at 2 years after therapy, acute and late toxicity.

Expected results: The expected complete response rate in patients treated with radiochemotherapy and those treated with radioimmunotherapy is 50% and 75%, respectively. We also expect the difference in an absolute survival gain between the groups to be 25%.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Squamous cell carcinoma, histologically proven (with HPV-status determined in patients with oropharyngeal primary)
  • Tumour site: oral cavity, oropharynx, hypopharynx or larynx.
  • Locally and/or regionally operable and inoperable tumors (UICC TNM stages III, IVa or IVb), without distant metastases (M0-stage)
  • Male or female ≥18 years of age
  • Expected survival >6 months
  • WHO performance status 0-2
  • Laboratory parameters:

hemoglobin ≥100 g/L; leukocyte count > 3.5x109/L, absolute neutrophil count ≥ 1.5x109/L; platelet count > 100x109/L; total bilirubin < 1.25x upper normal limit; transaminases (ALT, AST) < 5x upper normal limit; creatinine clearance (ECC) ≥ 60 ml/minute;

  • Presence of at least one bidimensionally measurable index lesion
  • Effective contraception for both male and female subjects if risk of conception exists
  • Signed written informed consent

Exclusion Criteria:

  • Other previous malignancy within 5 years, with exception of a history of a previously adequately treated basal cell carcinoma of the skin or pre- invasive carcinoma of the cervix
  • Chemotherapy ineligibility:

unstable cardiopulmonary, renal and liver disease likely to compromise the safe delivery of I.V. infusion (chemotherapy); haematologic diseases; clinically evident hearing impairment; pre-existing motor or sensory neurotoxicity grade ≥ 2 according to the CTCAE v3.0; previous administration of Cetuximab or Cisplatin;

  • Active, uncontrolled infection
  • Medical or psychological condition which in the opinion of the investigator precludes the safe administration of the planned radiotherapy or systemic therapy
  • Known drug abuse or severe alcohol abuse
  • Pregnancy or breast feeding
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01472653

Contacts
Contact: Primož Strojan, Prof. pstrojan@onko-i.si

Locations
Slovenia
Institute of Oncology Ljubljana Recruiting
Ljubljana, Slovenia, SI-1000
Contact: Primož Strojan, Prof.       pstrojan@onko-i.si   
Sub-Investigator: Marta Dremelj, MD, MSc         
Sub-Investigator: Igor Fajdiga, MD, PhD         
Sub-Investigator: Cvetka Kuhar Grašič, MD, PhD         
Sub-Investigator: Jančar Boris, MD, MSc         
Sub-Investigator: Simona Jereb, MD         
Sub-Investigator: Katarina Karner, MD, MSc         
Sub-Investigator: Barbara Žumer, MD         
Sponsors and Collaborators
Institute of Oncology Ljubljana
Investigators
Principal Investigator: Primož Strojan, Prof. Dept. of Radiation Oncology, Institute of Oncology Ljubljana, Slovenia
Principal Investigator: Branko Zakotnik, Prof. Dept. of Medical Oncology, Institute of Oncology Ljubljana, Slovenia
  More Information

No publications provided

Responsible Party: Institute of Oncology Ljubljana
ClinicalTrials.gov Identifier: NCT01472653     History of Changes
Other Study ID Numbers: ORL-01-11
Study First Received: October 23, 2011
Last Updated: December 11, 2011
Health Authority: Slovenia: Ethics Committee

Keywords provided by Institute of Oncology Ljubljana:
Head and neck Cancer
Radiochemotherapy
Radioimmunotherapy
Skin rush
locoregional control
Survival
Toxicity

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cetuximab
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 23, 2014