ECHO-07: Cetuximab and Combination Chemotherapy in Patients With Stage III-IV Resectable Oropharynx Cancer

Sponsor
GERCOR - Multidisciplinary Oncology Cooperative Group (Other)
Overall Status
Completed
CT.gov ID
NCT00665392
Collaborator
(none)
42
8
1
53
5.3
0.1

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

Study Type:
Interventional
Actual Enrollment :
42 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Induction Chemotherapy With Cetuximab, Docetaxel, Cisplatin, and Fluorouracil (ETPF) in Patient With Resectable Stage III-IV Squamous Cell Carcinoma of the Oropharynx
Study Start Date :
Feb 1, 2008
Actual Primary Completion Date :
Jul 1, 2012
Actual Study Completion Date :
Jul 1, 2012

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

  1. 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

  1. 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

  2. The 2-year Estimated Overall Survival (OS) Rate [2 years]

    2-year OS measured survival at 2 years from randomization.

  3. 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.

  4. The 2-year Estimated Progression-free Survival (PFS) [2 years]

    2-year PFS measured survival at 2 years from randomization.

  5. 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

  1. 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

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Responsible Party:
GERCOR - Multidisciplinary Oncology Cooperative Group
ClinicalTrials.gov Identifier:
NCT00665392
Other Study ID Numbers:
  • CDR0000593027
  • GERCOR-ECHO-07-1
  • 2007-002116-25
  • EU-20838
  • MERCK-GERCOR-ECHO-07-1
First Posted:
Apr 23, 2008
Last Update Posted:
Jun 25, 2021
Last Verified:
Aug 1, 2012
Keywords provided by GERCOR - Multidisciplinary Oncology Cooperative Group
Additional relevant MeSH terms:

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

1. Primary Outcome
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%
2. Secondary Outcome
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%
3. Secondary Outcome
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%
4. Secondary Outcome
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%
5. Secondary Outcome
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%
6. Secondary Outcome
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%
7. Other Pre-specified Outcome
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

[Not Specified]

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
Email regulatory.affairs@gercor.com.fr
Responsible Party:
GERCOR - Multidisciplinary Oncology Cooperative Group
ClinicalTrials.gov Identifier:
NCT00665392
Other Study ID Numbers:
  • CDR0000593027
  • GERCOR-ECHO-07-1
  • 2007-002116-25
  • EU-20838
  • MERCK-GERCOR-ECHO-07-1
First Posted:
Apr 23, 2008
Last Update Posted:
Jun 25, 2021
Last Verified:
Aug 1, 2012