Treatment Selection According to Skin Reaction to Cetuximab

Head and Neck Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01472653
• Other study ID #: ORL-01-11
• Status: Recruiting
• Phase: Phase 2
• First received: October 23, 2011
• Last updated: December 11, 2011
• Start date: December 2011
• Est. completion date: December 2016

Study information

• Verified date: December 2011
• Source: Institute of Oncology Ljubljana
• Contact: Primož Strojan, Prof.
• Email: pstrojan[@]onko-i.si
• Is FDA regulated: No
• Health authority: Slovenia: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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%.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 2016
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

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

Locations

Country	Name	City	State
Slovenia	Institute of Oncology Ljubljana	Ljubljana

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Oncology Ljubljana

Country where clinical trial is conducted

Slovenia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	locoregional complete response rate	The primary objective of the study is to determine radiologically the complete response rate 12-14 weeks after therapy.	12-14 weeks after therapy	No
Secondary	feasibility (toxicity profile) of the proposed regimen	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)	Yes
Secondary	locoregional control	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	No
Secondary	progression-free survival	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	No
Secondary	overall survival	Overall survival is defined as a time interval between the first day of therapy and death from any cause.	2 years after therapy	No
Secondary	late toxicity including thyroid function	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	Yes