A Phase II Study In Patients With Advanced Head And Neck Cancer Of Standard Chemoradiation And Add-On Cetuximab
Primary Purpose
Oropharyngeal Cancer, Hypopharyngeal Cancer, Laryngeal Cancer
Status
Completed
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
Cetuximab
Sponsored by
About this trial
This is an interventional treatment trial for Oropharyngeal Cancer
Eligibility Criteria
Inclusion criteria:
- T3-4 Nx M0; Tx N2b-3 M0 (N2b only if ≥ 3 ipsilateral nodes involved) and/or total GTV > 70 cc (any T, any N, M0)
- biopsy proven squamous cell cancer
- primary tumor location in oral cavity, oropharynx, hypopharynx or larynx
- Patients with CUP (cancer of unknown primary) syndrome in case they have advanced lymph node metastases (Tx N2b-3 M0 (N2b only if ≥ 3 ipsilateral nodes involved).- Indication for chemoradiation (RT + Cisplatin)
- curative treatment intent
- Start of chemoradiation within the recruitment time frame
- Performance Status WHO/ECOG: 0-1
- Age between 18 and 75 years
- No previous chemotherapy or RT for cancer of the head and neck
- Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study (until at least 60 days following the last study treatment
- Patient must sign informed consent prior to study entry.
Exclusion criteria:
- Cancer of the nasopharynx
- Any neoadjuvant chemotherapy prior to screening
- Treatment with other investigational drugs within 4 weeks
- History of malignancy other than basal cell skin cancer unless disease free for a minimum of 3 years.
- Uncontrolled claudication, bleeding, or thromboembolic disorders at screening
- Patients receiving heparin, warfarin or phenprocoumon therapy are ineligible- Uncontrolled and severe hypertension at screening according to the judgement of the investigator.
- Current uncontrolled cardiac disease: Unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, history of myocardial infarction within 12 months, significant arrhythmias
- Left ventricular function < 45 % (determination of left ventricular function required when history of cardiac disease)
- History of stroke within 6 months
- Major surgical procedure, or significant traumatic injury within 28 days prior to screening; anticipation of need for major surgical procedure during the course of the study.
- Acute bacterial or fungal infection requiring intravenous antibiotics at screening
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at screening
- Pregnant (positive pregnancy test) or lactating
- Previous organ transplantation
- Any immune suppressive therapy
- Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition because study treatment might be immuno-suppressive (Note: HIV testing only required if clinically indicated)
- Any uncontrolled condition, which in the opinion of the investigator, would interfere with the safe and timely completion of study procedures.
- Preexisting renal insufficiency with impaired creatinine clearance (<60ml/min) and/or increased plasma creatinine (>106 µmol/l) at screening
- History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 6 months prior to screening
- Serious, non-healing wound, ulcer, or bone fracture
- AST, ALT, or bilirubin > 1.5 x normal
- Preexisting absolute neutrophil count (ANC) < 1,800 cells/mm3
- Platelets < 100,000 103/µl at screening
- PTT > 1.5 x normal
- WBC < 4000 103/µl
- Hb < 11 g/dl at screening (Note: The use of transfusion or other intervention to achieve Hb > 11 g/dl is possible)
- Contraindication to CDDP
- Known allergy to cetuximab
Sites / Locations
- University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm A
Arm B
Arm Description
Patients will be treated with chemoradiation in combination with concurrent cetuximab. Two weeks after end of chemoradiation the consolidation phase will start and patients will receive biweekly consolidation cetuximab, maximally 6 infusions over 12 weeks.
Patients will be treated with chemoradiation in combination with concurrent cetuximab.
Outcomes
Primary Outcome Measures
Locoregional tumor control
Secondary Outcome Measures
Progression free survival (PFS)
Overall survival (OS)
Metastasis rate
Metastasis free survival (MFS)
Biological surrogate markers
Safety and tolerability
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01435252
Brief Title
A Phase II Study In Patients With Advanced Head And Neck Cancer Of Standard Chemoradiation And Add-On Cetuximab
Official Title
A Phase II, Randomized, Open-Label, Single Center Study In Patients With Advanced Head And Neck Cancer To Investigate Efficacy And Safety Of Standard Chemoradiation And Add-On Concurrent Cetuximab ± Consolidation Cetuximab
Study Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
September 19, 2011 (Actual)
Primary Completion Date
October 25, 2017 (Actual)
Study Completion Date
October 25, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Zurich
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Sixty patients with advanced squamous cell carcinomas of the head and neck will be enrolled in this study. Patients are treated with standard chemoradiation in combination with concurrent add-on cetuximab. Subsequently patients are randomized to cetuximab consolidation therapy (three months, Arm A) versus no consolidation therapy (Arm B). The aim of this study is to investigate if cetuximab consolidation therapy improves the 2-year locoregional control rate.
Trial with medicinal product
Trial with radiotherapy
Detailed Description
This clinical study translates our preclinical findings that concurrent and consolidation cetuximab improves efficacy of RT into the clinic. It is a phase II, randomized, open-label, single center study in patients with locoregionally advanced stage III-IV and/or total gross tumor volume (tGTV) > 70cc head and neck cancer. This study population is at high risk for locoregional recurrence after chemoradiation alone. Tumor stages to be included are T3-4 Nx, Tx N2b-N3 (N2b only if ≥ 3 ipsilateral nodes involved) M0 and/or tGTV >70 cc (any T, any N, M0) squamous cell cancers of the head and neck (HNSCC). All patients will receive in, the so called 'Induction Phase' standard chemoradiation (RT up to 70 Gy in combination with weekly CDDP 40 mg/m2) and add-on concurrent cetuximab (loading Dose 400 mg/m2, concurrent dose 250 mg/m2 weekly). The patients are randomized to either add-on consolidation cetuximab (500 mg/m2 biweekly x 6 over 12 weeks) (Arm A) or no further treatment (Arm B). Randomization will take place after Induction Phase. The total number of patients to be included into the study is 60 (30 patients per arm). Up to 6 patients may be replaced in case of early drop out to reach that aim.
The sample size of 60 patients is considered to be sufficient to collect first information on clinical efficacy and the possible impact of various biomarkers on clinical endpoints. If the results of this study will demonstrate that the novel treatment regimen is safe and efficacious, a randomized multicenter phase III study will follow.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oropharyngeal Cancer, Hypopharyngeal Cancer, Laryngeal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
68 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Experimental
Arm Description
Patients will be treated with chemoradiation in combination with concurrent cetuximab. Two weeks after end of chemoradiation the consolidation phase will start and patients will receive biweekly consolidation cetuximab, maximally 6 infusions over 12 weeks.
Arm Title
Arm B
Arm Type
Experimental
Arm Description
Patients will be treated with chemoradiation in combination with concurrent cetuximab.
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux®
Intervention Description
Arm A: chemoradiation in combination with concurrent cetuximab Arm B: chemoradiation in combination with concurrent and consolidation cetuximab
Primary Outcome Measure Information:
Title
Locoregional tumor control
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Progression free survival (PFS)
Time Frame
2 years
Title
Overall survival (OS)
Time Frame
2 years
Title
Metastasis rate
Time Frame
2 years
Title
Metastasis free survival (MFS)
Time Frame
2 years
Title
Biological surrogate markers
Time Frame
2 years
Title
Safety and tolerability
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
T3-4 Nx M0; Tx N2b-3 M0 (N2b only if ≥ 3 ipsilateral nodes involved) and/or total GTV > 70 cc (any T, any N, M0)
biopsy proven squamous cell cancer
primary tumor location in oral cavity, oropharynx, hypopharynx or larynx
Patients with CUP (cancer of unknown primary) syndrome in case they have advanced lymph node metastases (Tx N2b-3 M0 (N2b only if ≥ 3 ipsilateral nodes involved).- Indication for chemoradiation (RT + Cisplatin)
curative treatment intent
Start of chemoradiation within the recruitment time frame
Performance Status WHO/ECOG: 0-1
Age between 18 and 75 years
No previous chemotherapy or RT for cancer of the head and neck
Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study (until at least 60 days following the last study treatment
Patient must sign informed consent prior to study entry.
Exclusion criteria:
Cancer of the nasopharynx
Any neoadjuvant chemotherapy prior to screening
Treatment with other investigational drugs within 4 weeks
History of malignancy other than basal cell skin cancer unless disease free for a minimum of 3 years.
Uncontrolled claudication, bleeding, or thromboembolic disorders at screening
Patients receiving heparin, warfarin or phenprocoumon therapy are ineligible- Uncontrolled and severe hypertension at screening according to the judgement of the investigator.
Current uncontrolled cardiac disease: Unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure, history of myocardial infarction within 12 months, significant arrhythmias
Left ventricular function < 45 % (determination of left ventricular function required when history of cardiac disease)
History of stroke within 6 months
Major surgical procedure, or significant traumatic injury within 28 days prior to screening; anticipation of need for major surgical procedure during the course of the study.
Acute bacterial or fungal infection requiring intravenous antibiotics at screening
Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at screening
Pregnant (positive pregnancy test) or lactating
Previous organ transplantation
Any immune suppressive therapy
Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition because study treatment might be immuno-suppressive (Note: HIV testing only required if clinically indicated)
Any uncontrolled condition, which in the opinion of the investigator, would interfere with the safe and timely completion of study procedures.
Preexisting renal insufficiency with impaired creatinine clearance (<60ml/min) and/or increased plasma creatinine (>106 µmol/l) at screening
History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 6 months prior to screening
Serious, non-healing wound, ulcer, or bone fracture
AST, ALT, or bilirubin > 1.5 x normal
Preexisting absolute neutrophil count (ANC) < 1,800 cells/mm3
Platelets < 100,000 103/µl at screening
PTT > 1.5 x normal
WBC < 4000 103/µl
Hb < 11 g/dl at screening (Note: The use of transfusion or other intervention to achieve Hb > 11 g/dl is possible)
Contraindication to CDDP
Known allergy to cetuximab
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Oliver Riesterer, Leitender Arzt
Organizational Affiliation
University Hospital Zurich, Division of Radiation Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital
City
Zurich
Country
Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
31705729
Citation
de Galiza Barbosa F, Riesterer O, Tanadini-Lang S, Stieb S, Studer G, Pruschy M, Huber GF, Huellner MW, Stolzmann P, Veit-Haibach P. Evaluation of 18F-FDG PET/CT as an early imaging biomarker for response monitoring after radiochemotherapy using cetuximab in head and heck squamous cell carcinoma. Head Neck. 2020 Feb;42(2):163-170. doi: 10.1002/hed.25975. Epub 2019 Nov 9.
Results Reference
derived
Learn more about this trial
A Phase II Study In Patients With Advanced Head And Neck Cancer Of Standard Chemoradiation And Add-On Cetuximab
We'll reach out to this number within 24 hrs