Induction Chemotherapy Followed by Chemoradiation With Cetuximab in Head and Neck Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Institute of Oncology Ljubljana
ClinicalTrials.gov Identifier:
NCT00868491
First received: March 24, 2009
Last updated: October 23, 2011
Last verified: October 2011
  Purpose

The purpose of this study is to determine the efficacy and toxicity of docetaxel/cisplatin/5-fluorouracil induction chemotherapy (4 cycles) followed by concomitant chemoradiation with cetuximab and weekly cisplatin in patients with inoperable squamous cell carcinoma of the head and neck.


Condition Intervention Phase
Head and Neck Cancer
Drug: docetaxel, cisplatin, 5-fluorouracil
Radiation: radiotherapy
Drug: cetuximab, cisplatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Induction Chemotherapy Followed by Chemoradiation With Cetuximab and Cisplatin for Inoperable Squamous Cell Carcinoma of the Head and Neck

Resource links provided by NLM:


Further study details as provided by Institute of Oncology Ljubljana:

Primary Outcome Measures:
  • locoregional control [ Time Frame: at 2 years post-therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • feasibility (toxicity profile) of the proposed regimen [ Time Frame: during therapy ] [ Designated as safety issue: Yes ]
  • complete response rate [ Time Frame: after induction ChT and 14-16 weeks after the therapy ] [ Designated as safety issue: No ]
  • disease free survival [ Time Frame: at 2 years post-therapy ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: at 2 years post-therapy ] [ Designated as safety issue: No ]
  • late toxicity including thyroid function [ Time Frame: up to 2 years post-therapy ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: March 2008
Study Completion Date: October 2011
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: docetaxel, cisplatin, 5-fluorouracil
    docetaxel 75 mg/m2 I.V. day 1, cisplatin 75 mg/m2 I.V. day 1, 5-fluorouracil 750 mg/m2 I.V. continuous infusion days 1-5 repeated every 21 days for 4 cycles
    Radiation: radiotherapy
    Three-dimensional conformal radiotherapy planning and delivery (35x2 Gy/day over 7 weeks - weeks 14 - 20 of the study protocol
    Drug: cetuximab, cisplatin
    • cetuximab 400 mg/m2 I.V. week 13, cetuximab 250 mg/m2 I.V. weeks 14-20
    • cisplatin 30 mg/m2 I.V. weeks 14-20 (concomitantly with radiothrapy)
    Other Name: Erbitux
Detailed Description:

The treatment results with radiotherapy in inoperable squamous cell carcinoma of the head and neck are poor.

In this proposed single-institution non-randomized, one-arm, open label phase II study, the authors will test the efficacy and toxicity of docetaxel/cisplatin/5-fluorouracil induction chemotherapy (4 cycles) followed by concomitant chemoradiation with cetuximab and weekly cisplatin in patients with inoperable squamous cell carcinoma of the head and neck.

Chemotherapy doses will be as follows: docetaxel 75 mg/m2 I.V. day 1, cisplatin 75 mg/m2 I.V. day 1, 5-fluorouracil 750 mg/m2 I.V. continuous infusion days 1-5 repeated every 21 days for 4 cycles followed by cetuximab 400 mg/m2 I.V. week 13, cetuximab 250 mg/m2 I.V. weeks 14-20, cisplatin 30 mg/m2 I.V. weeks 14-20. Three-dimensional conformal radiotherapy planning and delivery (35x2 Gy/day over 7 weeks {weeks 14 - 20}) will be used.

The planned number of patients to be included is 30 and anticipated enrolment period is 12 months.

The primary objective of the study is to determine locoregional control at 2 years post-therapy, whereas secondary objectives are to determine feasibility (toxicity profile) of the proposed regimen, to determine complete response rate after induction ChT as well as 14-16 weeks after the therapy, completion of ChRT to determine disease free survival at 2 years, overall survival at 2 years and late toxicity including thyroid function.

Given the preliminary nature of the study, no stopping rule is prospectively planned outside of observed toxicity, which will be assessed and graded according to Common Terminology Criteria for Adverse Events version 3.0.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Squamous cell carcinoma, histologically proven
  • Tumour site: oral cavity, oropharynx, hypopharynx or larynx.
  • Locally and/or regionally inoperable tumors (UICC TNM stages IVa or IVb) - - without distant metastases (M0-stage)
  • Male or female ≥18 years of age
  • Expected survival >6 months
  • Presence of at least one bidimensionally measurable index lesion
  • Effective contraception for both male and female subjects if risk of conception exists
  • 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 ≥ 55 mls/minute

  • Signed written informed consent

Exclusion Criteria:

  • Metastatic disease
  • Squamous cell carcinoma of the nasopharynx and nasal cavity and paranasal sinuses
  • ChT or XRT ineligibility:

Unstable cardiac disease or any other medical condition likely to compromise the safe delivery of ChT or XRT; Clinically evident hearing impairment; Pre-existing motor or sensory neurotoxicity grade ≥ 2 according to the CTCAE v3.0;

  • Any kind of previous therapy for SCCHN (excluding diagnostic biopsy)
  • Previous administration of EGFR pathway-targeting therapy
  • Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy which is not part of the study protocol
  • Participation in another clinical trial within 30 days prior to study entry
  • Pregnancy or breast feeding
  • History of severe acute pulmonary disease
  • Any investigational agent within past 30 days
  • 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
  • Known drug abuse / severe alcohol abuse
  • Legal incapacity or limited legal capacity
  • Medical or psychological condition which in the opinion of the investigator would not permit the subject to complete the study or sign meaningful informed consent
  • Active, uncontrolled infection
  • Other medical condition or other therapy that in the opinion of the investigator precludes the safe administration of the planned ChT and XRT
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00868491

Locations
Slovenia
Institute of Oncology Ljubljana
Ljubljana, Slovenia, SI-1000
Sponsors and Collaborators
Institute of Oncology Ljubljana
Investigators
Principal Investigator: Primož Strojan, MD Dept. of Radiation Oncology, Institute of Oncology Ljubljana, Slovenia
  More Information

No publications provided

Responsible Party: Institute of Oncology Ljubljana
ClinicalTrials.gov Identifier: NCT00868491     History of Changes
Other Study ID Numbers: EMR-62202-717
Study First Received: March 24, 2009
Last Updated: October 23, 2011
Health Authority: Slovenia: Ethics Committee

Keywords provided by Institute of Oncology Ljubljana:
head and neck cancer
inoperable
induction chemotherapy
concomitant radiochemotherapy
biological agent
efficacy
toxicity

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Docetaxel
Cetuximab
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014