Recurrent or Metastatic Disease, Squamous Cell Head and Neck Carcinoma
Conditions
Keywords
Squamous cell carcinoma of the head and neck, recurrent or metastatic, first line chemotherapy, cetuximab, docetaxel, cisplatin, antineoplastic agents, First Line Palliative Treatment
Brief summary
PURPOSE: Cetuximab with platinum and 5FU is now the standard combination as first-line treatment in patients with metastatic or recurrent Head and Neck squamous cell carcinomas. Cetuximab and taxane combinations have demonstrated promising activity in Head and Neck cancer. This phase II trial is studying new cetuximab, docetaxel and cisplatin combination named TPEx as first-line treatment in this setting.
Detailed description
OBJECTIVES: Primary * To determine the efficacy of TPEx combination in patients with head and neck cancer in term of objective response rate (RECIST, see statistical consideration) Secondary * To assess toxicities of TPEx combination * Determine the efficacy of TPEx combination in patients with head and neck cancer: Best Overall Response , progression-free survival and survival. * Translational research objective:To better understand the mechanisms of chemoresistance and to identify biomarkers by the analysis of the tumor biopsies (RNA, gene expression profile) and protein profile (plasma samples). Exploratory analyses. OUTLINE: This is an open-label phase II, multicenter study. Patients receive four cycles of chemotherapy comprising cetuximab IV plus docetaxel IV over 1 hour and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of the fourth cycle of chemotherapy, patients receive a maintenance therapy with cetuximab every 2 weeks. Treatment will be continued until disease progression or unacceptable toxicities according to the patient or the investigator. Tumor check-up will be performed every 6 weeks. This study will allow translational research with blood sample and biopsies at baseline before any treatment, during the treatment with TPEx combination (week 6).,After completion of study treatment, patients are followed every 2 months.
Interventions
BIOLOGICALcetuximab IV
* Cetuximab 400 mg/m² over 120 minutes on day 1 of cycle 1 only. * Cetuximab dose will be 250 mg/m² IV over 60 minutes weekly on subsequent administrations during the four cycles of chemotherapy. * Cetuximab dose will be 500mg/m2 IV every 2 weeks during the maintenance therapy. Drug: Cisplatin IV : 75 mg/m2 intravenous every 3 weeks for 4 cycles Drug: Docetaxel IV : 75 mg/m2 intravenous every 3 weeks for 4 cycles G-CSF support with lenograstim 150 microg./m2/day is delivered after each cycle of chemotherapy.
OTHERBiopsies
No intervention, only biopsy for translational project.
Sponsors
Gustave Roussy, Cancer Campus, Grand Paris
Groupe Oncologie Radiotherapie Tete et Cou
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Histologically proven squamous cell carcinoma of the oral cavity, larynx, oropharynx or hypopharynx * Recurrent disease, incurable disease as determined by surgery or radiation, or metastatic disease * Measurable or evaluable disease * Age \> 18 years and \<= 70 years * WHO performance status 0 or 1 * Absolute neutrophil count \> 1,500/mm3 * Platelets \> 150,000/mm3 * Total Bilirubin \<= institutional upper limit of normal * Aspartate aminotransferase \< 1.5 X institutional upper limit of normal * Alanine aminotransferase \< 1.5 X institutional upper limit of normal * Alkaline phosphatase \< 2.5 X institutional upper limit of normal * creatinine clearance \> 60 mL/min * Signed informed consent * Women of child-bearing potential and men must be willing and able practice adequate contraception prior to study entry and for the duration of study treatment
Exclusion criteria
* Previous chemotherapy. Chemotherapy given as part of initial curative therapy and completed more than 6 months before inclusion is allowed * Previous treatment with total doses of cisplatin \> 300 mg/ m2 * Patients must not have any co-existing disease that would preclude cisplatin administration, such as peripheral neuropathy or renal failure * Surgery (excluding biopsy) or radiotherapy within 4 weeks prior to study entry * Nasopharyngeal carcinoma, or cancer of sinusal cavities * Active infection including tuberculosis or HIV positive patient * Other malignancy within last 5 years except for non-melanoma skin cancer * No other investigational agent within 30 days prior to study entry * No other concurrent chemotherapy, immunotherapy, antitumor hormonal therapy (excluding contraceptives and replacement steroids), radiotherapy, or experimental medications * No prior anti EGFR therapy * No known brain metastases * Uncontrolled intercurrent illness that would prevent delivery of protocol therapy * Patients with a prior history of basal cell carcinoma of the skin or in situ carcinoma of the cervix must have been curatively treated and must have remained disease free for 5 years post diagnosis * No history of hypersensitivity reaction to drugs on study * No unstable angina or myocardial infarction within the past 12 months * No symptomatic congestive heart failure or New York Heart Association (NYHA) class II-IV heart disease * No serious uncontrolled cardiac arrhythmia * No other prior or concomitant squamous cell carcinoma * No other prior or concomitant cancer, except curatively treated basal carcinoma of the skin or in situ cervical cancer, for which the patient has been curatively treated and remains disease-free for the past 5 years * Patient is pregnant or lactating * Patients must not have any co-existing condition that would preclude full compliance with the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Tumor Response Rate | 12 weeks (after completion of the 4th cycle of chemotherapy) | The objective tumor response rate is evaluated every 6 weeks according to RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT-scan or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biomarkers | two years | — |
| Grade 1 to 5 Toxicity | 24 weeks (average) | All grade 1 to 5 toxicity are registered during treatment. Patients have weekly clinical and biological examination. |
| Best Overall Response | 12 weeks | Tumor response is evaluated every 6 weeks according to RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions, Stable Disease (SD); Best overall Response = CR + PR + SD. |
| Progression-free Survival | 1 year | — |
| Overall Survival | 1 year | — |
Countries
Belgium, France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab Patients receive four cycles of chemotherapy comprising cetuximab IV plus docetaxel IV over 1 hour and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of the fourth cycle of chemotherapy, patients receive a maintenance therapy with cetuximab every 2 weeks. Treatment will be continued until disease progression or unacceptable toxicities according cetuximab IV: - 400 mg/m² over 120 minutes on day 1 of cycle 1 only.
* 250 mg/m² IV over 60 minutes weekly on subsequent administrations during the four cycles of chemotherapy.
* 500mg/m2 IV every 2 weeks during the maintenance therapy.
Drug: Cisplatin IV : 75 mg/m2 every 3 weeks for 4 cycles Drug: Docetaxel IV : 75 mg/m2 every 3 weeks for 4 cycles
G-CSF support with lenograstim 150 microg./m2/day is delivered after each cycle of chemotherapy.
Biopsies: No intervention, only biopsy for translational project. | 54 |
| Total | 54 |
Baseline characteristics
| Characteristic | Cetuximab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants |
| Age, Continuous | 57.8 years |
| Region of Enrollment Belgium | 8 participants |
| Region of Enrollment France | 46 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 35 / 54 |
| serious Total, serious adverse events | 15 / 54 |
Outcome results
Primary
Objective Tumor Response Rate
The objective tumor response rate is evaluated every 6 weeks according to RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT-scan or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.
Time frame: 12 weeks (after completion of the 4th cycle of chemotherapy)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab | Objective Tumor Response Rate | 44 percentage of participants |
Secondary
Best Overall Response
Tumor response is evaluated every 6 weeks according to RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions, Stable Disease (SD); Best overall Response = CR + PR + SD.
Time frame: 12 weeks
Population: 2 patients not assessable for response at 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab | Best Overall Response | 53.7 percentage of Best overall ORR |
Secondary
Biomarkers
Time frame: two years
Secondary
Grade 1 to 5 Toxicity
All grade 1 to 5 toxicity are registered during treatment. Patients have weekly clinical and biological examination.
Time frame: 24 weeks (average)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab | Grade 1 to 5 Toxicity | 50 percentage of events |
Secondary
Overall Survival
Time frame: 1 year
Secondary
Progression-free Survival
Time frame: 1 year