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| ID | Type | Description | Link |
|---|---|---|---|
| GERCOR-ECHO-07-1 | Other Identifier | GERCOR | |
| 2007-002116-25 | EudraCT Number | ||
| EU-20838 | Registry Identifier | EU Clinical Trials Register | |
| MERCK-GERCOR-ECHO-07-1 | Other Identifier | GERCOR |
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RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as docetaxel, cisplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with cetuximab may kill more tumor cells.
PURPOSE: This phase II clinical trial is studying how well cetuximab given together with combination chemotherapy works in treating patients with stage III or stage IV oropharynx cancer that can be removed by surgery.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study.
Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15; docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1; and fluorouracil IV continuously on days 1-5. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed every 2 months for 1 year and every 3 months for 2 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| cetuximab | Experimental | Cetuximab by intravenous (IV) infusion over 1-2 h on day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cisplatin | Drug | 75 mg/m², day 1. 3 cycles |
| |
| docetaxel |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical and Radiological Complete Clinical Response (crCR) Rate at 3 Months | The evaluation of tumor response rate was assessed by computed tomography scan of the neck and chest at Baseline, then at 3 months from inclusion using RECIST1.0 criteria and clinical examination | at 3 months after ETPF combination |
| Measure | Description | Time Frame |
|---|---|---|
| Complete Clinical Response (cCR) | Clinical complete response (cCR) is defined by:
The evaluation of tumor response rate was assessed by computed tomography scan of the neck and chest at Baseline, then at 3 months from inclusion using RECIST1.0 criteria and clinical examination |
| Measure | Description | Time Frame |
|---|---|---|
| Biomarkers Analysis - HPV Genotyping | correlative studies investigating HPV status in tumor and blood samples obtained prior to and after induction therapy were done for exploratory purposes as planned in the protocol |
DISEASE CHARACTERISTICS:
Histologically confirmed squamous cell carcinoma of the oropharynx
Measurable or evaluable disease
Tumor tissue available
PATIENT CHARACTERISTICS:
Inclusion criteria:
Exclusion criteria:
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Jean Lacau Saint Guily, MD | Hopital Tenon | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Simone Veil | Montmorency | 95160 | France | |||
| Hôpital Privé St Joseph |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25684313 | Result | Chibaudel B, Lacave R, Lefevre M, Soussan P, Antoine M, Perie S, Belloc JB, Banal A, Albert S, Chabolle F, Ceruse P, Baril P, Gatineau M, Housset M, Moukoko R, Benetkiewicz M, de Gramont A, Bonnetain F, Lacau St Guily J. Induction therapy with cetuximab plus docetaxel, cisplatin, and 5-fluorouracil (ETPF) in patients with resectable nonmetastatic stage III or IV squamous cell carcinoma of the oropharynx. A GERCOR phase II ECHO-07 study. Cancer Med. 2015 May;4(5):721-31. doi: 10.1002/cam4.408. Epub 2015 Feb 14. |
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The main inclusion criteria: Previously untreated, resectable stage III (T3 or T1 - 2N1 - 2M0) to IVB (T4 or T1 -3N3M0) SCCHN of the oropharynx, measurable or evaluable disease, WHO performance status ≤ 1, adequate hematologic, renal and liver functions.
The main exclusion criteria: uncontrolled cardiac or other disease, hearing impairment
From July 2008 to April 2013, 42 patients were enrolled. This study was conducted in France, in 9 active centers: Hospital Tenon, HEGP, Hospital Bichat, GH St Joseph Paris, Hospital Foch Suresnes, CH Lyon Sud, Hospital Delafontaine St Denis, Centre René Huguenin St Cloud et Hospital Simone Veil Montmorency.
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| ID | Title | Description |
|---|---|---|
| FG000 | ETPF Adminstration | cisplatin: 75 mg/m², day 1. 3 cycles docetaxel: 75 mg/m² Day 1. 3 cycles fluorouracil: 750 mg/m² day 1 to day 5. 3 cycles Cetuximab: 400 mg/m² Day 1, 250 mg/m² Day 8 and Day 15. 3 cycles. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Drug |
75 mg/m² Day 1. 3 cycles |
|
| fluorouracil | Drug | 750 mg/m² day 1 to day 5. 3 cycles |
|
| Cetuximab | Drug | 400 mg/m² Day 1, 250 mg/m² Day 8 and Day 15. 3 cycles. |
|
| at 3 months |
| The 2-year Estimated Overall Survival (OS) Rate | 2-year OS measured survival at 2 years from randomization. | 2 years |
| Pathologic Response | On primary tumor resected : measure of persistence or not of tumoral lesion, histological type, size and quality of the excision piece A pathological complete response is defined as no viable tumour cells detected on histological examination post surgery. | after surgery of the primary tumor |
| The 2-year Estimated Progression-free Survival (PFS) | 2-year PFS measured survival at 2 years from randomization. | 2 years |
| Complete Radiological Response (rCR) | Radiological response is defined according to RECIST 1.0 criteria:
| At 3 months after the end of 3 cycles of the ETPF combination |
| Paris |
| 75014 |
| France |
| Hopital Europeen Georges Pompidou | Paris | 75015 | France |
| Hopital Bichat - Claude Bernard | Paris | 75018 | France |
| Hopital Tenon | Paris | 75970 | France |
| centre Hospitalier Lyon Sud | Pierre-Bénite | 69495 | France |
| Centre René Huguenin | Saint-Cloud | 92100 | France |
| Hopital Foch | Suresnes | 92151 | France |
| COMPLETED |
|
| NOT COMPLETED |
|
|
42 patients enrolled and 41 treated. Forty-one patients (mITT population) started induction therapy. One patient did not receive an intended treatment due to investigator decision to replace cisplatin by carboplatin and not to administer cetuximab.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cetuximab | cisplatin: 75 mg/m², day 1. 3 cycles docetaxel: 75 mg/m² Day 1. 3 cycles fluorouracil: 750 mg/m² day 1 to day 5. 3 cycles Cetuximab: 400 mg/m² Day 1, 250 mg/m² Day 8 and Day 15. 3 cycles. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Region of Enrollment | Number | participants |
| |||||||||||||||||||||||
| Grade of differentiation | Number | participants |
| |||||||||||||||||||||||
| Primary tumor localization | Number | participants |
| |||||||||||||||||||||||
| T-stage | Classification for Oropharyngeal - T for Primary tumor TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ T1 Tumor ≤2 cm in greatest dimension T2 Tumor >2 cm but not more than 4cm in greatest dimension T3 Tumor >4 cm in greatest dimension or extension to lingual surface of the epiglottis T4a Moderately advanced, local disease T4b Very advanced, local disease | Number | participants |
| ||||||||||||||||||||||
| N-stage | N for Regional lymph nodes N0 No regional lymph node metastasis N1 Metastasis in a single ipsilateral lymph node ≤3 cm in greatest dimension N2 Metastasis in a single ipsilateral lymph node >3 cm but not more than 6cm in greatest dimension; or in multiple ipsilateral lymph nodes, none >6cm in greatest dimension; or in bilateral or contralateral lymph nodes, none >6cm in greatest dimension N3 Metastasis in a lymph node >6cm in greatest dimension | Number | participants |
| ||||||||||||||||||||||
| Cancer Staging at the inclusion | Patient with resectable stade III (T3 or T1 - 2N1 - 2M0) to IVB (T4 or T1- 3N 3M0). Anatomic stage/prognostic groups at the inclusion. Stade III is the best pronostic than stade IV. | Number | participants |
| ||||||||||||||||||||||
| Lip mobility | Number | participants |
| |||||||||||||||||||||||
| Trismus | Number | participants |
| |||||||||||||||||||||||
| Creatinine clearance (mL/min) | Number | participants |
| |||||||||||||||||||||||
| Albuminemia (g/L) | Number | participants |
| |||||||||||||||||||||||
| Life style risk factors | Number | participants |
| |||||||||||||||||||||||
| HPV 16 status | human papillomavirus type 16 status | Number | participants |
| ||||||||||||||||||||||
| ECOG performance status | The ECOG Performance Status is a method to assess the functional status of a patient.
| Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Clinical and Radiological Complete Clinical Response (crCR) Rate at 3 Months | The evaluation of tumor response rate was assessed by computed tomography scan of the neck and chest at Baseline, then at 3 months from inclusion using RECIST1.0 criteria and clinical examination | Posted | Number | participants | at 3 months after ETPF combination |
|
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Complete Clinical Response (cCR) | Clinical complete response (cCR) is defined by:
The evaluation of tumor response rate was assessed by computed tomography scan of the neck and chest at Baseline, then at 3 months from inclusion using RECIST1.0 criteria and clinical examination | Posted | Number | participants | at 3 months |
|
| ||||||||||||||||||||||||||||||||||||||
| Secondary | The 2-year Estimated Overall Survival (OS) Rate | 2-year OS measured survival at 2 years from randomization. | Median OS was not achieved. The 2-year estimated rate is given. | Posted | Number | percentage of participants | 2 years |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Pathologic Response | On primary tumor resected : measure of persistence or not of tumoral lesion, histological type, size and quality of the excision piece A pathological complete response is defined as no viable tumour cells detected on histological examination post surgery. | Pathological response is evaluable in patients with tumor surgical resection only | Posted | Number | participants | after surgery of the primary tumor |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | The 2-year Estimated Progression-free Survival (PFS) | 2-year PFS measured survival at 2 years from randomization. | Posted | Number | percentage of participants | 2 years |
|
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Complete Radiological Response (rCR) | Radiological response is defined according to RECIST 1.0 criteria:
| Patients in the mITT population who received ETPF | Posted | Number | participants | At 3 months after the end of 3 cycles of the ETPF combination |
|
| |||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Biomarkers Analysis - HPV Genotyping | Posted | Number | participants | correlative studies investigating HPV status in tumor and blood samples obtained prior to and after induction therapy were done for exploratory purposes as planned in the protocol |
|
|
Until 1 month after the last administration
Adverse events (AE) were collected during induction treatment and follow-up visit (1 month).Toxicity evaluation was carried out according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v3.0)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ETPF Administration | cisplatin: 75 mg/m², day 1. 3 cycles docetaxel: 75 mg/m² Day 1. 3 cycles fluorouracil: 750 mg/m² day 1 to day 5. 3 cycles Cetuximab: 400 mg/m² Day 1, 250 mg/m² Day 8 and Day 15. 3 cycles. | 13 | 41 | 41 | 41 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypovolaemia | Vascular disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Orthostatic hypotension | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment | grade 3 |
|
| Acute pancreatitis | Hepatobiliary disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Febrile aplasia | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
| |
| sepsis | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
| |
| Febrile neutropenia | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
| |
| Infection at the portacath site | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Creatinine | Blood and lymphatic system disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA (Unspecified) | Systematic Assessment |
| |
| Febrile neutropenia | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Regulatory Affairs | GERCOR | +33 (0)1 40 29 85 00 | regulatory.affairs@gercor.com.fr |
| ID | Term |
|---|---|
| D006258 | Head and Neck Neoplasms |
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| D014062 | Tongue Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009062 | Mouth Neoplasms |
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
| D014060 | Tongue Diseases |
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| ID | Term |
|---|---|
| D002945 | Cisplatin |
| D000077143 | Docetaxel |
| D005472 | Fluorouracil |
| D000068818 | Cetuximab |
| ID | Term |
|---|---|
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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| Poor or undifferentiated |
|
| Missing |
|
| Posterior |
|
| Superior |
|
|
| T4 |
|
|
| N2 |
|
| N3 |
|
| > 120 |
|
| Missing |
|
| Missing |
|
| Alcohol + Tobacco |
|
| None |
|
| Missing |
|
| Title | Measurements |
|---|---|
|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
|
| Title | Denominators | Categories |
|---|
|
|
| Title | Denominators | Categories |
|---|
| HPV16 - Positive |
| |||||
| HPV16 - Negative |
|