ECHO-07: Cetuximab and Combination Chemotherapy in Patients With Stage III-IV Resectable Oropharynx Cancer
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Detailed Description
OBJECTIVES:
Primary
- To determine the complete clinical response rate at 3 months in patients with stage III or IV nonmetastatic squamous cell carcinoma of the oropharynx treated with cetuximab, docetaxel, cisplatin, and fluorouracil.
Secondary
-
To determine the rate of tumor response.
-
To determine progression-free and overall survival.
-
To determine the rate of complete pathological response.
-
To assess the tolerability of this regimen in these patients.
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: cetuximab Cetuximab by intravenous (IV) infusion over 1-2 h on day |
Drug: cisplatin
75 mg/m², day 1. 3 cycles
Drug: docetaxel
75 mg/m² Day 1. 3 cycles
Drug: fluorouracil
750 mg/m² day 1 to day 5. 3 cycles
Drug: Cetuximab
400 mg/m² Day 1, 250 mg/m² Day 8 and Day 15. 3 cycles.
|
Outcome Measures
Primary Outcome Measures
- Clinical and Radiological Complete Clinical Response (crCR) Rate at 3 Months [at 3 months after ETPF combination]
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
Secondary Outcome Measures
- Complete Clinical Response (cCR) [at 3 months]
Clinical complete response (cCR) is defined by: Disappearance of all clinical evidence of visible tumor, Disappearance of all palpable residual infiltration, Disappearance of all evidence of residual visible tumor on CT scan in pharynx and parapharyngeal space, Complete symmetric remobilization of the tongue and amygdala. Disappearance of pre-existing trismus. Negative control biopsy. 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
- The 2-year Estimated Overall Survival (OS) Rate [2 years]
2-year OS measured survival at 2 years from randomization.
- Pathologic Response [after surgery of the primary tumor]
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.
- The 2-year Estimated Progression-free Survival (PFS) [2 years]
2-year PFS measured survival at 2 years from randomization.
- Complete Radiological Response (rCR) [At 3 months after the end of 3 cycles of the ETPF combination]
Radiological response is defined according to RECIST 1.0 criteria: Complete response (CR): disappearance of all target lesions Partial response (PR): at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter, Progressive disease (PD): at least a 20% increase in the sum of the longest diameter of target the appearance of one or more new lesions, Stable disease (SD): neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started
Other Outcome Measures
- 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]
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
-
Histologically confirmed squamous cell carcinoma of the oropharynx
-
Stage III (T3 or T1-2, N1-2, M0) or nonmetastatic stage IV (T4 or T1-3, N3, M0) disease
-
Resectable disease
-
Measurable or evaluable disease
-
Tumor tissue available
PATIENT CHARACTERISTICS:
Inclusion criteria:
-
WHO performance status 0-1
-
ANC ≥ 1,500/mm3
-
Platelet count ≥ 100,000/mm3
-
Hemoglobin ≥ 9 g/dL
-
Creatinine < 1.5 times upper limit of normal (ULN)
-
Creatinine clearance ≥ 60 mL/min
-
AST and ALT < 5 times ULN
-
Bilirubin < 1.5 times ULN
-
Not pregnant or nursing
-
Fertile patients must use effective contraception
-
Affiliated with social security (including CMU)
Exclusion criteria:
-
Cardiovascular accident (myocardial infarction, cerebral vascular accident) within the past 6 months
-
Serious and/or uncontrolled cardiac or respiratory disease (pulmonary fibrosis, interstitial pneumopathy)
-
Other cancer within the past 5 years except for resected skin cancer, localized cutaneous or totally resected melanoma, or resected carcinoma in situ of the cervix
-
Auditory condition precluding the use of cisplatin
-
Contraindication due to psychological, social, or geographical reasons that may impede proper monitoring of treatment
-
Persons under guardianship or trusteeship, or prisoners of law
PRIOR CONCURRENT THERAPY:
-
No prior treatment, including chemotherapy or radiotherapy
-
No concurrent phenytoin, live attenuated vaccines, or parenteral aminoglycosides
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Hôpital Simone Veil | Montmorency | France | 95160 | |
2 | Hôpital Privé St Joseph | Paris | France | 75014 | |
3 | Hopital Europeen Georges Pompidou | Paris | France | 75015 | |
4 | Hopital Bichat - Claude Bernard | Paris | France | 75018 | |
5 | Hopital Tenon | Paris | France | 75970 | |
6 | centre Hospitalier Lyon Sud | Pierre Benite | France | 69495 | |
7 | Centre René Huguenin | Saint Cloud | France | 92100 | |
8 | Hopital Foch | Suresnes | France | 92151 |
Sponsors and Collaborators
- GERCOR - Multidisciplinary Oncology Cooperative Group
Investigators
- Principal Investigator: Jean Lacau Saint Guily, MD, Hopital Tenon
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- CDR0000593027
- GERCOR-ECHO-07-1
- 2007-002116-25
- EU-20838
- MERCK-GERCOR-ECHO-07-1
Study Results
Participant Flow
Recruitment Details | 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. |
---|---|
Pre-assignment Detail | 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 |
Arm/Group Title | ETPF Adminstration |
---|---|
Arm/Group Description | 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. |
Period Title: Overall Study | |
STARTED | 42 |
COMPLETED | 41 |
NOT COMPLETED | 1 |
Baseline Characteristics
Arm/Group Title | Cetuximab |
---|---|
Arm/Group Description | 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. |
Overall Participants | 42 |
Age (years) [Mean (Standard Deviation) ] | |
Mean (Standard Deviation) [years] |
56.1
(6.8)
|
Sex: Female, Male (Count of Participants) | |
Female |
8
19%
|
Male |
34
81%
|
Region of Enrollment (participants) [Number] | |
France |
42
100%
|
Grade of differentiation (participants) [Number] | |
Well |
17
40.5%
|
Moderate |
18
42.9%
|
Poor or undifferentiated |
4
9.5%
|
Missing |
3
7.1%
|
Primary tumor localization (participants) [Number] | |
Anterior |
3
7.1%
|
Lateral (tonsillar area) |
37
88.1%
|
Posterior |
1
2.4%
|
Superior |
1
2.4%
|
T-stage (participants) [Number] | |
T2 |
13
31%
|
T3 |
24
57.1%
|
T4 |
5
11.9%
|
N-stage (participants) [Number] | |
N0 |
5
11.9%
|
N1 |
9
21.4%
|
N2 |
27
64.3%
|
N3 |
1
2.4%
|
Cancer Staging at the inclusion (participants) [Number] | |
III |
32
76.2%
|
IV |
10
23.8%
|
Lip mobility (participants) [Number] | |
Normal |
40
95.2%
|
Decreased |
2
4.8%
|
Trismus (participants) [Number] | |
Yes |
5
11.9%
|
No |
37
88.1%
|
Creatinine clearance (mL/min) (participants) [Number] | |
< 60 |
1
2.4%
|
60 -120 |
31
73.8%
|
> 120 |
8
19%
|
Missing |
2
4.8%
|
Albuminemia (g/L) (participants) [Number] | |
< 40 |
8
19%
|
≥ 60 |
14
33.3%
|
Missing |
20
47.6%
|
Life style risk factors (participants) [Number] | |
Alcohol |
3
7.1%
|
Tobacco |
8
19%
|
Alcohol + Tobacco |
25
59.5%
|
None |
6
14.3%
|
HPV 16 status (participants) [Number] | |
Positive |
17
40.5%
|
Negative |
25
59.5%
|
ECOG performance status (participants) [Number] | |
ECOG - PS=0 |
33
78.6%
|
ECOG - PS=1 |
8
19%
|
Missing |
1
2.4%
|
Outcome Measures
Title | Clinical and Radiological Complete Clinical Response (crCR) Rate at 3 Months |
---|---|
Description | 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 |
Time Frame | at 3 months after ETPF combination |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | ETPF Administration |
---|---|
Arm/Group Description | 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. |
Measure Participants | 41 |
Tumor response Rate - Tumor |
9
21.4%
|
Tumor response rate - node |
8
19%
|
Tumor response rate - Tumor and node |
4
9.5%
|
Title | Complete Clinical Response (cCR) |
---|---|
Description | Clinical complete response (cCR) is defined by: Disappearance of all clinical evidence of visible tumor, Disappearance of all palpable residual infiltration, Disappearance of all evidence of residual visible tumor on CT scan in pharynx and parapharyngeal space, Complete symmetric remobilization of the tongue and amygdala. Disappearance of pre-existing trismus. Negative control biopsy. 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 |
Time Frame | at 3 months |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | ETPF Administration |
---|---|
Arm/Group Description | 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. |
Measure Participants | 41 |
Tumor response rate - tumor |
17
40.5%
|
Tumor response rate - node |
15
35.7%
|
Tumor response rate - Tumor and node |
13
31%
|
Title | The 2-year Estimated Overall Survival (OS) Rate |
---|---|
Description | 2-year OS measured survival at 2 years from randomization. |
Time Frame | 2 years |
Outcome Measure Data
Analysis Population Description |
---|
Median OS was not achieved. The 2-year estimated rate is given. |
Arm/Group Title | ETPF Administration |
---|---|
Arm/Group Description | 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. |
Measure Participants | 41 |
Number [percentage of participants] |
82
195.2%
|
Title | Pathologic Response |
---|---|
Description | 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. |
Time Frame | after surgery of the primary tumor |
Outcome Measure Data
Analysis Population Description |
---|
Pathological response is evaluable in patients with tumor surgical resection only |
Arm/Group Title | ETPF Administration |
---|---|
Arm/Group Description | 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. |
Measure Participants | 22 |
Number [participants] |
9
21.4%
|
Title | The 2-year Estimated Progression-free Survival (PFS) |
---|---|
Description | 2-year PFS measured survival at 2 years from randomization. |
Time Frame | 2 years |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | ETPF Administration |
---|---|
Arm/Group Description | 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. |
Measure Participants | 41 |
Number [percentage of participants] |
64
152.4%
|
Title | Complete Radiological Response (rCR) |
---|---|
Description | Radiological response is defined according to RECIST 1.0 criteria: Complete response (CR): disappearance of all target lesions Partial response (PR): at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter, Progressive disease (PD): at least a 20% increase in the sum of the longest diameter of target the appearance of one or more new lesions, Stable disease (SD): neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started |
Time Frame | At 3 months after the end of 3 cycles of the ETPF combination |
Outcome Measure Data
Analysis Population Description |
---|
Patients in the mITT population who received ETPF |
Arm/Group Title | ETPF Administration |
---|---|
Arm/Group Description | Treatment consisted of cetuximab by intravenous (IV) infusion over 1-2 h on days 1, 8, and 15 (loading dose of 400 mg/m2 on day 1, then 250 mg/m2 weekly) followed the same day by docetaxel and cisplatin both given as a 1h IV infusion (at a 75 mg/m2 dose) and by 5-FU IV infusion on days 1-5 (at a 750 mg/m2 dose per day). Treatment was given every 3 weeks for a maximum of three cycles. |
Measure Participants | 41 |
Tumor response rate - Tumor |
14
33.3%
|
Tumor response rate - Node |
8
19%
|
Tumor response rate - Tumor and node |
4
9.5%
|
Title | Biomarkers Analysis - HPV Genotyping |
---|---|
Description | |
Time Frame | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | ETPF Administration |
---|---|
Arm/Group Description | 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. |
Measure Participants | 42 |
HPV16 - Positive |
17
40.5%
|
HPV16 - Negative |
25
59.5%
|
Adverse Events
Time Frame | Until 1 month after the last administration | |
---|---|---|
Adverse Event Reporting Description | 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) | |
Arm/Group Title | ETPF Administration | |
Arm/Group Description | 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. | |
All Cause Mortality |
||
ETPF Administration | ||
Affected / at Risk (%) | # Events | |
Total | / (NaN) | |
Serious Adverse Events |
||
ETPF Administration | ||
Affected / at Risk (%) | # Events | |
Total | 13/41 (31.7%) | |
Cardiac disorders | ||
Orthostatic hypotension | 1/41 (2.4%) | |
Cardiac arrest | 1/41 (2.4%) | 1 |
Gastrointestinal disorders | ||
Vomiting | 2/41 (4.9%) | |
Diarrhoea | 3/41 (7.3%) | |
Hepatobiliary disorders | ||
Acute pancreatitis | 1/41 (2.4%) | |
Infections and infestations | ||
Febrile aplasia | 2/41 (4.9%) | |
sepsis | 1/41 (2.4%) | |
Febrile neutropenia | 1/41 (2.4%) | |
Infection at the portacath site | 2/41 (4.9%) | |
Renal and urinary disorders | ||
Renal failure | 1/41 (2.4%) | |
Vascular disorders | ||
Hypovolaemia | 1/41 (2.4%) | |
Other (Not Including Serious) Adverse Events |
||
ETPF Administration | ||
Affected / at Risk (%) | # Events | |
Total | 41/41 (100%) | |
Blood and lymphatic system disorders | ||
Neutropenia | 18/41 (43.9%) | |
Anemia | 33/41 (80.5%) | |
Thrombocytopenia | 9/41 (22%) | |
Creatinine | 9/41 (22%) | |
Gastrointestinal disorders | ||
Nausea | 16/41 (39%) | |
Vomiting | 13/41 (31.7%) | |
Stomatitis | 14/41 (34.1%) | |
Diarrhoea | 27/41 (65.9%) | |
Infections and infestations | ||
Febrile neutropenia | 8/41 (19.5%) | |
Nervous system disorders | ||
Neuropathy peripheral | 4/41 (9.8%) | |
Skin and subcutaneous tissue disorders | ||
Acne | 18/41 (43.9%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Regulatory Affairs |
---|---|
Organization | GERCOR |
Phone | +33 (0)1 40 29 85 00 |
regulatory.affairs@gercor.com.fr |
- CDR0000593027
- GERCOR-ECHO-07-1
- 2007-002116-25
- EU-20838
- MERCK-GERCOR-ECHO-07-1