Zalutumumab in Combination With Radiotherapy in Head and Neck Cancer Patients Ineligible for Platinum Based Chemotherapy

This study has been terminated.
(The decision is based on company re-evaluation of indications to be pursued within SCCHN)
Sponsor:
Information provided by (Responsible Party):
Genmab
ClinicalTrials.gov Identifier:
NCT00707655
First received: June 27, 2008
Last updated: November 21, 2011
Last verified: November 2011
  Purpose

The purpose of this study is to investigate the safety of zalutumumab in combination with radiotherapy as the treatment of patients with head and neck cancer who are not eligible for platinum based chemotherapy.


Condition Intervention Phase
Head and Neck Cancer
Squamous Cell Carcinoma
Drug: Zalutumumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, International, Multi-Center, Phase I/II, Dose-escalation Trial Investigating the Safety of Zalutumumab, a Human Monoclonal Epidermal Growth Factor Receptor Antibody in Combination With Radiotherapy, in Patients With Stage III, IVa or IVb Locally Advanced Squamous Cell Carcinoma of the Head and Neck Ineligible for Platinum Based Chemotherapy

Resource links provided by NLM:


Further study details as provided by Genmab:

Primary Outcome Measures:
  • Adverse Events [ Time Frame: Overall study ] [ Designated as safety issue: Yes ]
    Number of participants with at least one adverse event. All adverse events are collected during 12 weeks and all serious adverse events are collected during 2 years.


Secondary Outcome Measures:
  • Best Overall Tumour Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Best overall tumor response according to RECIST criteria J Natl Cancer Inst 2000;92:205-16 assessed by CT/MRI. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the longest diameter of target lesions; Overall Response (OR), CR+PR

  • Tumor Response Rate/ Complete or Partial Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: September 2008
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zalutumumab 4 mg/kg
Zalutumumab in combination with radiotherapy for 8 weeks. The treatment period of 8 weeks is followed by a 3 week follow-up period where all adverse events are collected and then additionally a 2 year follow-up period where only serious adverse events are collected.
Drug: Zalutumumab
Eight weekly infusions
Experimental: Zalutumumab 8 mg/kg
Zalutumumab in combination with radiotherapy for 8 weeks. The treatment period of 8 weeks is followed by a 3 week follow-up period where all adverse events are collected and then additionally a 2 year follow-up period where only serious adverse events are collected.
Drug: Zalutumumab
Eight weekly infusions

Detailed Description:

This is an open label, multi-center, phase I/II dose-escalation clinical trial investigating the safety of zalutumumab in combination with radiotherapy. The safety of zalutumumab doses in combination with radiotherapy (RT) will be investigated using 3 patient cohorts in a dose-escalation / de-escalation design based on Dose Limiting Toxicity (DLT). The dose-escalation starts at 8 mg/kg zalutumumab in combination with RT. Initially, three patients will be treated at a dose level and observed for DLTs. If none of the three patients experience a DLT, then the next cohort of three patients is treated at the next higher dose of zalutumumab. If one of three patients treated at a dose level experience a DLT, then three more patients are treated at the same dose level. If two or more of the three patients experience DLTs, then the next cohort of three patients should be treated at the next lower dose of zalutumumab, unless at least six patients on that dose have already been dosed. Furthermore, if 1 or fewer DLTs are observed among six patients at a given dose level, then the next cohort of three patients is treated at the next higher dose of zalutumumab. The maximum tolerated dose will be decided by Genmab based on the recommendations made by the IDMC on the basis of their review of the aggregated safety data.

  Eligibility

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

Inclusion Criteria:

  1. Patients with histologically or cytologically confirmed diagnosis of locally advanced squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx stage III, IVa or IVb
  2. Measurable disease defined as one or more target lesions according to RECIST based onCT scan or MRI and clinical evaluation
  3. Eligible for intended curative radiotherapy
  4. Patients considered ineligible for platinum based chemotherapy based on investigator's judgment
  5. Age > 18 years
  6. Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out

Exclusion Criteria:

  1. Prior radiotherapy to the head and neck area
  2. Prior chemotherapy administered for cancer in the head and neck area
  3. Prior targeted therapy (e.g. EGFR antibodies or EGFR inhibitors)
  4. Received the following treatments within 4 weeks prior to Visit 2:

    1. Retinoic acid
    2. Other immunosuppressive drugs (e.g. drugs interfering with the functions of T cells, IL-2 or equivalent)
    3. Any non-marketed drug substance
  5. Past or current malignancy other than SCCHN, except for:

    • Cervical carcinoma Stage 1B or less
    • Non-invasive basal cell skin carcinoma
    • Squamous cell skin carcinoma
    • Stage 1 or 2 treated prostate cancer with PSA in the normal range for >2 years post treatment
    • Malignant melanoma with a complete response duration of > 10 years
    • Other cancer diagnoses with a complete response duration of > 5 years
  6. Metastatic SCCHN disease
  7. Chronic or current infectious disease such as, but not limited to, chronic renal infection and tuberculosis
  8. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months before Visit 1, congestive heart failure, and arrhythmia requiring anti-arrhythmic therapy, with the exception of extra systoles or minor conduction abnormalities
  9. Significant concurrent, uncontrolled medical condition including, but not limited to,hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease considered to preclude trial treatment and/or compliance according to the Investigator's opinion, or any other condition preventing therapy according to the Investigator's opinion
  10. Known HIV positive
  11. Known active hepatitis B and/or hepatitis C
  12. Screening laboratory values:

    • Neutrophils < 1.5 x 109/L
    • Platelets < 100 x109/L
    • Hemoglobin < 6 mmol/L
  13. Current participation in any other interventional clinical study
  14. Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency, or psychological disorder)
  15. Known or suspected hypersensitivity to components of the investigational medicinal Product
  16. Breast feeding women or women with a positive pregnancy test at screening blood Sample
  17. Males not willing to use adequate contraception during study and for 12 months after last dose of zalutumumab or women of childbearing potential not willing to use adequate contraception as hormonal birth control or intrauterine device during study and for 12 months after last dose of zalutumumab
  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: NCT00707655

Locations
Belgium
St-Luc University Hospital
Brussels, Belgium
France
Centre Georges-Francois Leclerc Hospital
Dijon, France
Medical Oncology, Outpatient Clinic
Nantes, France
Institut Claudius Regaud Toulouse
Toulouse, France
United Kingdom
St James's Institute of Oncology
Leeds, United Kingdom, LS9 7TF
The Royal Marsden NHS Foundation Trust
London, United Kingdom
Christie Hospital NHS Foundation Trust
Manchester, United Kingdom
Sheffield Teaching Hospitals NHS Foundation Trust
Sheffield, United Kingdom
Sponsors and Collaborators
Genmab
Investigators
Principal Investigator: Philippe MAIGON Centre Georges-François Leclerc
  More Information

No publications provided

Responsible Party: Genmab
ClinicalTrials.gov Identifier: NCT00707655     History of Changes
Other Study ID Numbers: GEN207
Study First Received: June 27, 2008
Results First Received: October 7, 2011
Last Updated: November 21, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Belgium: Federal Agency for Medicines and Health Products, FAMHP
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014