- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01472653
Treatment Selection According to Skin Reaction to Cetuximab
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
Study Overview
Status
Conditions
Intervention / Treatment
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%.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Primož Strojan, Prof.
- Email: pstrojan@onko-i.si
Study Locations
-
-
-
Ljubljana, Slovenia, SI-1000
- Recruiting
- Institute of Oncology Ljubljana
-
Contact:
- Primož Strojan, Prof.
- Email: 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
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
locoregional complete response rate
Time Frame: 12-14 weeks after therapy
|
The primary objective of the study is to determine radiologically the complete response rate 12-14 weeks after therapy.
|
12-14 weeks after therapy
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
feasibility (toxicity profile) of the proposed regimen
Time Frame: participants will be followed for the duration of treatment (an expected average of 20 weeks)
|
number of patients with adverse events graded according to the National Cancer Institute CTC v3.0 (as measure of safety and tolerability)
|
participants will be followed for the duration of treatment (an expected average of 20 weeks)
|
locoregional control
Time Frame: at 2 years after thapy
|
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.
|
at 2 years after thapy
|
progression-free survival
Time Frame: 2 years after therapy
|
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.
|
2 years after therapy
|
overall survival
Time Frame: 2 years after therapy
|
Overall survival is defined as a time interval between the first day of therapy and death from any cause.
|
2 years after therapy
|
late toxicity including thyroid function
Time Frame: up to 2 years post-therapy
|
number of patients with adverse events graded according to the National Cancer Institute CTC v3.0 (as measure of safety and tolerability)
|
up to 2 years post-therapy
|
Collaborators and Investigators
Sponsor
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
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ORL-01-11
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Head and Neck Cancer
-
Robert FerrisAmgenCompletedHead and Neck Cancer | Cancer of Head and Neck | Head Cancer | Neck Cancer | Neoplasms, Head and Neck | Cancer of the Head and Neck | Cancer of Neck | Upper Aerodigestive Tract Neoplasms | Neck Neoplasms | Cancer of the Head | Cancer of the Neck | UADT Neoplasms | Cancer of Head | Head Neoplasms | Head, Neck Neoplasms | Neoplasms, Head and other conditionsUnited States
-
Assiut UniversityRecruitingHead and Neck Cancer | Head and Neck Neoplasms | Cancer of Head and Neck | Neoplasms, Head and Neck | Cancer of the Head and NeckEgypt
-
Mayo ClinicRecruitingCancer Head Neck | Cancer Neck | Cancer, HeadUnited States
-
IRCCS Policlinico S. MatteoNestlé Health Science Spain; Akern SrlCompletedHead-neck CancerItaly
-
University of California, San FranciscoCompleted
-
Chinook Therapeutics, Inc. (formerly Aduro)TerminatedRecurrent Head and Neck Cancer | Metastatic Head and Neck CancerUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)TerminatedHead And Neck CancerUnited States
-
National Cancer Institute (NCI)TerminatedRecurrent Head and Neck Cancer | Metastatic Head and Neck CancerUnited States
-
Centre Oscar LambretUnknownEpidermoid Head and Neck CancerFrance
-
Radboud University Medical CenterUnknown
Clinical Trials on cisplatin
-
Insmed IncorporatedCompletedOsteosarcoma MetastaticUnited States
-
West China Second University HospitalRecruitingNeoadjuvant Chemotherapy | Epithelial Carcinoma, OvarianChina
-
Privo TechnologiesNational Cancer Institute (NCI)CompletedOral Squamous Cell CarcinomaUnited States
-
Samsung Medical CenterUnknownNasophayngeal Carcinoma Between Stage II and IVbKorea, Republic of
-
Cedars-Sinai Medical CenterRecruitingHPV Positive Oropharyngeal Squamous Cell CarcinomaUnited States
-
Korea Cancer Center HospitalCompletedCervical CancersKorea, Republic of
-
Taiho Oncology, Inc.Quintiles, Inc.Completed
-
Sun Yat-sen UniversityActive, not recruitingNasopharyngeal CarcinomaChina
-
Lawson Health Research InstituteRecruitingLocally Advanced Head and Neck Squamous Cell CarcinomaCanada
-
Sun Yat-sen UniversityFirst Affiliated Hospital, Sun Yat-Sen University; Guangdong Provincial People... and other collaboratorsActive, not recruitingNasopharyngeal Carcinoma | Nasopharyngeal Neoplasms | Nasopharyngeal Diseases | Head and Neck NeoplasmChina