Head and Neck CancerPhase 2NCT01084083
Induction Chemotherapy Followed By Cetuximab and Radiation in HPV-Associated Resectable Stage III/IV Oropharynx Cancer
A Phase 2 study testing cetuximab, intensity-modulated radiation therapy (IMRT) and Paclitaxel in people with Head and Neck Cancer and Precancerous Condition, run by Eastern Cooperative Oncology Group at 121 sites in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as paclitaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Precancerous Condition
- What is being tested?
- cetuximab, intensity-modulated radiation therapy (IMRT) and Paclitaxel
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 121 sitesUnited States
- Study dates
- 11 Aug 2010to Jan 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed squamous cell carcinoma of the oropharynx as determined by Hematoxylin and eosin (H\&E) staining
- Newly diagnosed disease
- Resectable disease OR disease that is expected to become resectable after study treatment
- Stage III, IVA, or IVB disease as determined by imaging studies (computed tomography (CT) scan with IV contrast or magnetic resonance imaging (MRI) required) and a complete head and neck exam
- Paraffin-embedded tumor specimen available for central confirmation of HPV-associated disease as determined by H\&E staining and in-situ hybridization (ISH) for HPV-16 and immunohistochemistry (IHC) for p16
- HPV-associated disease is defined as p16 IHC-positive and/or HPV-16 ISH-positive
Show all 24Show fewer
- Non-HPV-associated disease is defined as p16 IHC-negative
- NOTE: If there is limited tumor material, p16 IHC will be performed before HPV-16 ISH
- Measurable disease of the primary tumor or nodes by clinical and radiographic methods, defined as a lesion that is ≥ 2 cm in at least one dimension by clinical exam AND by radiographic exam with CT scan or MRI (or a lesion that is ≥ 1 cm in at least one dimension if the radiographic exam utilizes spiral CT scan)
- No primary tumor or nodal metastasis fixed to the carotid artery, skull base, or cervical spine
- No evidence of distant metastases
- Eastern Cooperative Oncology Group performance status 0-1
- Granulocytes ≥ 1,000/mm^3
- Platelet count ≥ 100,000/mm^3
- Total serum bilirubin ≤ 1.5 mg/dL
- Creatinine clearance ≥ 60 mL/min
- Negative pregnancy test
- Fertile patients must use effective contraception
- No history of another malignancy (except for carcinoma in situ of the cervix and/or nonmelanomatous skin cancer) unless it has been curatively treated and the patient has been disease-free for ≥ 2 years
- Patients with any of the following within the past 6 months are eligible provided they have been evaluated by a cardiologist and/or neurologist before study entry:
- New York Heart Association (NYHA) class III-IV congestive heart failure
- Cerebrovascular accident or transient ischemic attack
- Unstable angina
- Myocardial infarction (with or without ST elevation)
Who cannot join
- Prior chemotherapy
- Prior radiotherapy above the clavicles
- Prior surgery with curative intent for this disease (complete head and neck exam with biopsy allowed)
- Prior therapy specifically and directly targeting the EGFR pathway
- Prior severe infusion reaction to a monoclonal antibody
- Uncontrolled diabetes, uncontrolled infection despite antibiotics, or uncontrolled hypertension within the past 30 days
- Concurrent illness likely to interfere with study therapy or to prevent surgical resection
- Pregnant or nursing
Trial locations and contacts
121 sites in 1 country.
121 sites in 1 country
United States121 sites
Hickman Cancer Center at Bixby Medical Center
Adrian, Michigan, 49221
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87131-5636
Aurora Presbyterian Hospital
Aurora, Colorado, 80012
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231-2410
Mary Bird Perkins Cancer Center - Baton Rouge
Baton Rouge, Louisiana, 70809
UAB Comprehensive Cancer Center
Birmingham, Alabama, 35294
Boulder Community Hospital
Boulder, Colorado, 80301-9019
Wood County Oncology Center
Bowling Green, Ohio, 43402
Fairview Ridges Hospital
Burnsville, Minnesota, 55337
Butler Memorial Hospital
Butler, Pennsylvania, 16001
Cancer Center of Kansas, PA - Chanute
Chanute, Kansas, 66720
Medical Oncology and Hematology Associates - West Des Moines
Clive, Iowa, 50325
North Coast Cancer Care - Clyde
Clyde, Ohio, 43410
Penrose Cancer Center at Penrose Hospital
Colorado Springs, Colorado, 80933
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, 55433
St. Anthony Central Hospital
Denver, Colorado, 80204
Porter Adventist Hospital
Denver, Colorado, 80210
Presbyterian - St. Luke's Medical Center
Denver, Colorado, 80218
St. Joseph Hospital
Denver, Colorado, 80218
Rose Medical Center
Denver, Colorado, 80220
CCOP - Colorado Cancer Research Program
Denver, Colorado, 80224-2522
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, 50309
John Stoddard Cancer Center at Iowa Methodist Medical Center
Des Moines, Iowa, 50309
Medical Oncology and Hematology Associates at John Stoddard Cancer Center
Des Moines, Iowa, 50309
Medical Oncology and Hematology Associates at Mercy Cancer Center
Des Moines, Iowa, 50314
Mercy Cancer Center at Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314
John Stoddard Cancer Center at Iowa Lutheran Hospital
Des Moines, Iowa, 50316
Cancer Center of Kansas, PA - Dodge City
Dodge City, Kansas, 67801
Fairview Southdale Hospital
Edina, Minnesota, 55435
Cancer Center of Kansas, PA - El Dorado
El Dorado, Kansas, 67042
Union Hospital of Cecil County
Elkton, Maryland, 21921
Community Cancer Center
Elyria, Ohio, 44035
Hematology Oncology Center
Elyria, Ohio, 44035
Swedish Medical Center
Englewood, Colorado, 80110
Evanston Hospital
Evanston, Illinois, 60201-1781
CCOP - MeritCare Hospital
Fargo, North Dakota, 58122
Fergus Falls Medical Group, PA
Fergus Falls, Minnesota, 56537
Poudre Valley Hospital
Fort Collins, Colorado, 80524
Front Range Cancer Specialists
Fort Collins, Colorado, 80528
Vanderbilt-Ingram Cancer Center - Cool Springs
Franklin, Tennessee, 37067
Fredericksburg Oncology, Incorporated
Fredericksburg, Virginia, 22401
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, 55432
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
Grand Junction, Colorado, 81502
North Colorado Medical Center
Greeley, Colorado, 80631
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, 54307-3508
California Cancer Care, Incorporated - Greenbrae
Greenbrae, California, 94904
Hutchinson Area Health Care
Hutchinson, Minnesota, 55350
Borgess Medical Center
Kalamazoo, Michigan, 49001
West Michigan Cancer Center
Kalamazoo, Michigan, 49007-3731
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
Cancer Center of Kansas, PA - Kingman
Kingman, Kansas, 67068
Lawrence Memorial Hospital
Lawrence, Kansas, 66044
Tunnell Cancer Center at Beebe Medical Center
Lewes, Delaware, 19958
Cancer Center of Kansas, PA - Liberal
Liberal, Kansas, 67901
Lima Memorial Hospital
Lima, Ohio, 45804
Sky Ridge Medical Center
Lone Tree, Colorado, 80124
Hope Cancer Care Center at Longmont United Hospital
Longmont, Colorado, 80501
McKee Medical Center
Loveland, Colorado, 80539
Holy Family Memorial Medical Center Cancer Care Center
Manitowoc, Wisconsin, 54221-1450
HealthEast Cancer Care at St. John's Hospital
Maplewood, Minnesota, 55109
Minnesota Oncology Hematology, PA - Maplewood
Maplewood, Minnesota, 55109
Bay Area Cancer Care Center at Bay Area Medical Center
Marinette, Wisconsin, 54143
Northwest Ohio Oncology Center
Maumee, Ohio, 43537-1839
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, 55407
Hennepin County Medical Center - Minneapolis
Minneapolis, Minnesota, 55415
Community Cancer Center of Monroe
Monroe, Michigan, 48162
Mercy Memorial Hospital - Monroe
Monroe, Michigan, 48162
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838
George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus
New Britain, Connecticut, 06050
MBCCOP - LSU Health Sciences Center
New Orleans, Louisiana, 70112
Medical Center of Louisiana - New Orleans
New Orleans, Louisiana, 70112
CCOP - Christiana Care Health Services
Newark, Delaware, 19713
Cancer Center of Kansas, PA - Newton
Newton, Kansas, 67114
Fisher-Titus Medical Center
Norwalk, Ohio, 44857
Regional Cancer Center at Oconomowoc Memorial Hospital
Oconomowoc, Wisconsin, 53066
St. Charles Mercy Hospital
Oregon, Ohio, 43616
Toledo Clinic - Oregon
Oregon, Ohio, 43616
Veterans Affairs Medical Center - Palo Alto
Palo Alto, California, 94304
Cancer Center of Kansas, PA - Parsons
Parsons, Kansas, 67357
Fox Chase Cancer Center - Philadelphia
Philadelphia, Pennsylvania, 19111-2497
UPMC Cancer Centers
Pittsburgh, Pennsylvania, 15232
Cancer Center of Kansas, PA - Pratt
Pratt, Kansas, 67124
St. Mary - Corwin Regional Medical Center
Pueblo, Colorado, 81004
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
Robbinsdale, Minnesota, 55422-2900
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, 55416
Park Nicollet Cancer Center
Saint Louis Park, Minnesota, 55416
Regions Hospital Cancer Care Center
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
Cancer Center of Kansas, PA - Salina
Salina, Kansas, 67401
North Coast Cancer Care, Incorporated
Sandusky, Ohio, 44870
St. Francis Cancer Center at St. Francis Medical Center
Shakopee, Minnesota, 55379
St. Nicholas Hospital
Sheboygan, Wisconsin, 53081
Siouxland Hematology-Oncology Associates, LLP
Sioux City, Iowa, 51101
Mercy Medical Center - Sioux City
Sioux City, Iowa, 51104
St. Luke's Regional Medical Center
Sioux City, Iowa, 51104
Stanford Cancer Center
Stanford, California, 94305-5824
Stony Brook University Cancer Center
Stony Brook, New York, 11794-9446
Flower Hospital Cancer Center
Sylvania, Ohio, 43560
North Suburban Medical Center
Thornton, Colorado, 80229
Mercy Hospital of Tiffin
Tiffin, Ohio, 44883
Toledo Hospital
Toledo, Ohio, 43606
St. Vincent Mercy Medical Center
Toledo, Ohio, 43608
Medical University of Ohio Cancer Center
Toledo, Ohio, 43614
CCOP - Toledo Community Hospital
Toledo, Ohio, 43617
St. Anne Mercy Hospital
Toledo, Ohio, 43623
Toledo Clinic, Incorporated - Main Clinic
Toledo, Ohio, 43623
Natalie Warren Bryant Cancer Center at St. Francis Hospital
Tulsa, Oklahoma, 74136
Cancer Institute of New Jersey at Cooper - Voorhees
Voorhees Township, New Jersey, 08043
Ridgeview Medical Center
Waconia, Minnesota, 55387
Waukesha Memorial Hospital Regional Cancer Center
Waukesha, Wisconsin, 53188
Fulton County Health Center
Wauseon, Ohio, 43567
Cancer Center of Kansas, PA - Wellington
Wellington, Kansas, 67152
Exempla Lutheran Medical Center
Wheat Ridge, Colorado, 80033
Associates in Womens Health, PA - North Review
Wichita, Kansas, 67208
Cancer Center of Kansas, PA - Medical Arts Tower
Wichita, Kansas, 67208
Cancer Center of Kansas, PA - Wichita
Wichita, Kansas, 67214
CCOP - Wichita
Wichita, Kansas, 67214
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, 67214
Willmar Cancer Center at Rice Memorial Hospital
Willmar, Minnesota, 56201
Cancer Center of Kansas, PA - Winfield
Winfield, Kansas, 67156
Minnesota Oncology Hematology, PA - Woodbury
Woodbury, Minnesota, 55125
About this study
Official title: A Phase II Trial of Induction Chemotherapy Followed by Cetuximab (Erbitux) With Low Dose vs. Standard Dose IMRT in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx
RATIONALE: Drugs used in chemotherapy, such as paclitaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Radiation therapy uses high energy x-rays to kill tumor cells. Giving paclitaxel, cisplatin, and cetuximab together with radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying paclitaxel, cisplatin, and cetuximab to see how well they work when followed by cetuximab and two different doses of intensity-modulated radiation therapy in treating patients with HPV-associated stage III or stage IV cancer of the oropharynx that can be removed by surgery.
Read the detailed description
OBJECTIVES:
Primary
- To evaluate the efficacy of induction therapy comprising paclitaxel, cisplatin, and cetuximab followed by cetuximab in combination with low-dose or standard-dose intensity-modulated radiotherapy, as measured by 2-year progression-free survival (PFS), in patients with human papillomavirus(HPV)-associated resectable stage III-IVB squamous cell carcinoma of the oropharynx.
Secondary
- To assess overall survival.
- To evaluate the objective response, local control, and metastatic rate.
- To evaluate early and late toxicities of treatment.
Tertiary
- To evaluate quality of life and speech and swallowing function as measured by Functional Assessment of Cancer Therapy - General (FACT-G), Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN), and Vanderbilt Head and Neck Symptom Survey (VHNSS).
- To assess the effect of treatment-induced fatigue on general physical functioning in patients with head and neck cancer.
- To correlate functional decline with clinical, physical, and biologic correlatives.
- To evaluate radiation-resistance markers, including ERCC1 single nucleotide polymorphism and protein expression, and to correlate them with treatment efficacy.
- To demonstrate the usefulness of biomarkers, including ERCC1, epidermal growth factor receptor (EGFR), cytokine and chemokine markers, and plasma transforming growth factor alpha (TGFA) and transforming growth factor beta (TGFB) levels, in predicting progression-free survival (PFS) and other outcome parameters.
- To evaluate the correlation between the efficacy of cetuximab and polymorphisms in FcγR-receptors.
- To evaluate functional outcome and biological parameters, including telomere length, angiotensin-converting enzyme polymorphism, and C-reactive protein level.
OUTLINE: This is a multicenter study.
- Induction therapy: Patients receive cisplatin intravenously (IV) over 1 hour on day 1 and paclitaxel IV over 3 hours and cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for 3 courses. Patients then undergo evaluation of response to induction therapy. Patients with a clinical complete response (CR) at the primary tumor site proceed to group 1 of concurrent radiotherapy and cetuximab. Patients with a clinical partial response (PR) or stable disease (SD) at the primary tumor site or those with grossly positive disease at the primary tumor site proceed to group 2 of concurrent radiotherapy and cetuximab.
- Concurrent radiotherapy and cetuximab: Treatment begins 14-21 days after the last day of induction therapy.
- Group 1 (CR): Patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 5 weeks (27 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 6 weeks.
- Group 2 (PR, SD, or grossly positive disease): Patients undergo standard-dose IMRT 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 7 weeks.
Patients complete questionnaires assessing fatigue, physical function, weight loss, quality of life, head and neck symptom burden, and speech and swallowing function at baseline and at 1, 6, 12, and 24 months after completion of study treatment.
Tumor tissue and serum samples may be collected periodically for correlative laboratory studies.
After completion of study treatment, patients are followed up periodically for 3 years.
PROJECTED ACCRUAL: 83 patients
- Conditions
- Head and Neck Cancer, Precancerous Condition
- Being tested
- cetuximab, intensity-modulated radiation therapy (IMRT), Paclitaxel, Cisplatin
- Keywords
- human papilloma virus infection, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, tongue cancer
- Medical subject headings
- Head and Neck Neoplasms, Precancerous Conditions, Papillomavirus Infections, Squamous Cell Carcinoma of Head and Neck, Tongue Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cetuximabBiological
Given IV
intensity-modulated radiation therapy (IMRT)Radiation
Patients undergo low-dose OR standard dose IMRT based on their clinical response to induction therapy
PaclitaxelDrug
Also called Abraxane, Taxol
Given IV, 90 mg/m^2 on days 1, 8 and 15
CisplatinDrug
Also called Platinol
Given IV, 75 mg/m^2 on day 1
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | After induction therapy with Paclitaxel and Cisplatin, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 5 weeks (27 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 6 weeks. Receives: Biological: cetuximab; Radiation: intensity-modulated radiation therapy (IMRT); Drug: Paclitaxel; Drug: Cisplatin |
| Group 2 | Experimental | After induction therapy with Paclitaxel and Cisplatin, patients undergo standard-dose IMRT 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 7 weeks. Receives: Biological: cetuximab; Radiation: intensity-modulated radiation therapy (IMRT); Drug: Paclitaxel; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-month Progression-free Survival
24-month progression-free survival is defined as the proportion of patients who were alive and progression-free at 24 months post registration. The primary study population for this endpoint is patients who were confirmed post-induction clinical complete response (CR) at their primary sites and subsequently received 5400 cGy radiation therapy to their primary sites.
Measured: assessed within 14 days after delivery of the third cycle of induction therapy, and 8 weeks and 6 months after completion of concurrent therapy, then every 6 months until progression or until 3 years from study entry
Secondary outcomes (2)
24-months Overall Survival
OS was defined as the time from registration to death, or censored at last date known alive. Kaplan-Meier method was used to estimate the overall survival rate at 24 months.
Measured: assessed within 14 days after delivery of the third cycle of induction therapy, and 8 weeks and 6 months after completion of concurrent therapy, then every 6 months until progression or until 3 years from study entry
Primary Clinical Response Rate
Primary clinical response rate is defined as the proportion of patients with complete response or partial response at their primary sites after induction therapy. Response status for the primary site was classified by clinical examination using endoscopy. If, however, the clinical response status of the primary was unclear based on endoscopy, then the CT or MRI (required at the end of induction) was used to determine status of the primary. If clinical and radiological evaluation of the primary was unclear, a biopsy was considered at the discretion of the treating physician.
Measured: assessed within 14 days after delivery of the third cycle of induction therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2010 (estimated)
- Study start11 Aug 2010
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eastern Cooperative Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Shanthi Marur, MD, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01084083
- Sponsor's protocol ID
- CDR0000665170
- Other IDs
- ECOG-E1308, U10CA023318
- Status last verified
- Jun 2023
- First submitted
- 9 Mar 2010
- Last updated
- 28 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Marur S, Li S, Cmelak AJ, Gillison ML, Zhao WJ, Ferris RL, Westra WH, Gilbert J, Bauman JE, Wagner LI, Trevarthen DR, Balkrishna J, Murphy BA, Agrawal N, Colevas AD, Chung CH, Burtness B. E1308: Phase II Trial of Induction Chemotherapy Followed by Reduced-Dose Radiation and Weekly Cetuximab in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx- ECOG-ACRIN Cancer Research Group. J Clin Oncol. 2017 Feb 10;35(5):490-497. doi: 10.1200/JCO.2016.68.3300. Epub 2016 Dec 28.
PubMed 28029303Psyrri A, Rampias T, Vermorken JB. The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck. Ann Oncol. 2014 Nov;25(11):2101-2115. doi: 10.1093/annonc/mdu265. Epub 2014 Jul 23.
PubMed 25057165
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Induction Chemotherapy Followed by Cetuximab (Erbitux) With Low Dose vs. Standard Dose IMRT in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx
- ClinicalTrials.gov ID
- NCT01084083
- Acronym / sponsor ID
- CDR0000665170
- Conditions
- Head and Neck Cancer, Precancerous Condition
- Keywords
- human papilloma virus infection, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, tongue cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Eastern Cooperative Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 11 Aug 2010 (actual)
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 10 Mar 2010 (estimated)
- Results
- Posted 28 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as paclitaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Radiation therapy uses high energy x-rays to kill tumor cells. Giving paclitaxel, cisplatin, and cetuximab together with radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying paclitaxel, cisplatin, and cetuximab to see how well they work when followed by cetuximab and two different doses of intensity-modulated radiation therapy in treating patients with HPV-associated stage III or stage IV cancer of the oropharynx that can be removed by surgery.
Detailed description
OBJECTIVES:
Primary
- To evaluate the efficacy of induction therapy comprising paclitaxel, cisplatin, and cetuximab followed by cetuximab in combination with low-dose or standard-dose intensity-modulated radiotherapy, as measured by 2-year progression-free survival (PFS), in patients with human papillomavirus(HPV)-associated resectable stage III-IVB squamous cell carcinoma of the oropharynx.
Secondary
- To assess overall survival.
- To evaluate the objective response, local control, and metastatic rate.
- To evaluate early and late toxicities of treatment.
Tertiary
- To evaluate quality of life and speech and swallowing function as measured by Functional Assessment of Cancer Therapy - General (FACT-G), Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN), and Vanderbilt Head and Neck Symptom Survey (VHNSS).
- To assess the effect of treatment-induced fatigue on general physical functioning in patients with head and neck cancer.
- To correlate functional decline with clinical, physical, and biologic correlatives.
- To evaluate radiation-resistance markers, including ERCC1 single nucleotide polymorphism and protein expression, and to correlate them with treatment efficacy.
- To demonstrate the usefulness of biomarkers, including ERCC1, epidermal growth factor receptor (EGFR), cytokine and chemokine markers, and plasma transforming growth factor alpha (TGFA) and transforming growth factor beta (TGFB) levels, in predicting progression-free survival (PFS) and other outcome parameters.
- To evaluate the correlation between the efficacy of cetuximab and polymorphisms in FcγR-receptors.
- To evaluate functional outcome and biological parameters, including telomere length, angiotensin-converting enzyme polymorphism, and C-reactive protein level.
OUTLINE: This is a multicenter study.
- Induction therapy: Patients receive cisplatin intravenously (IV) over 1 hour on day 1 and paclitaxel IV over 3 hours and cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for 3 courses. Patients then undergo evaluation of response to induction therapy. Patients with a clinical complete response (CR) at the primary tumor site proceed to group 1 of concurrent radiotherapy and cetuximab. Patients with a clinical partial response (PR) or stable disease (SD) at the primary tumor site or those with grossly positive disease at the primary tumor site proceed to group 2 of concurrent radiotherapy and cetuximab.
- Concurrent radiotherapy and cetuximab: Treatment begins 14-21 days after the last day of induction therapy.
- Group 1 (CR): Patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 5 weeks (27 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 6 weeks.
- Group 2 (PR, SD, or grossly positive disease): Patients undergo standard-dose IMRT 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 7 weeks.
Patients complete questionnaires assessing fatigue, physical function, weight loss, quality of life, head and neck symptom burden, and speech and swallowing function at baseline and at 1, 6, 12, and 24 months after completion of study treatment.
Tumor tissue and serum samples may be collected periodically for correlative laboratory studies.
After completion of study treatment, patients are followed up periodically for 3 years.
PROJECTED ACCRUAL: 83 patients
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Biological: cetuximab, Radiation: intensity-modulated radiation therapy (IMRT), Drug: Paclitaxel, Drug: CisplatinAfter induction therapy with Paclitaxel and Cisplatin, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 5 weeks (27 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 6 weeks. |
| Group 2 | Experimental | Biological: cetuximab, Radiation: intensity-modulated radiation therapy (IMRT), Drug: Paclitaxel, Drug: CisplatinAfter induction therapy with Paclitaxel and Cisplatin, patients undergo standard-dose IMRT 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 7 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Histologically or cytologically confirmed squamous cell carcinoma of the oropharynx as determined by Hematoxylin and eosin (H\&E) staining
- Paraffin-embedded tumor specimen available for central confirmation of HPV-associated disease as determined by H\&E staining and in-situ hybridization (ISH) for HPV-16 and immunohistochemistry (IHC) for p16
- Measurable disease of the primary tumor or nodes by clinical and radiographic methods, defined as a lesion that is ≥ 2 cm in at least one dimension by clinical exam AND by radiographic exam with CT scan or MRI (or a lesion that is ≥ 1 cm in at least one dimension if the radiographic exam utilizes spiral CT scan)
- No primary tumor or nodal metastasis fixed to the carotid artery, skull base, or cervical spine
- No evidence of distant metastases
Key exclusion criteria (8 listed)
- Prior chemotherapy
- Prior radiotherapy above the clavicles
- Prior surgery with curative intent for this disease (complete head and neck exam with biopsy allowed)
- Prior therapy specifically and directly targeting the EGFR pathway
- Prior severe infusion reaction to a monoclonal antibody
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cetuximabGiven IV | Biological | Group 1, Group 2 |
| intensity-modulated radiation therapy (IMRT)Patients undergo low-dose OR standard dose IMRT based on their clinical response to induction therapy | Radiation | Group 1, Group 2 |
| PaclitaxelAlso: Abraxane, TaxolGiven IV, 90 mg/m^2 on days 1, 8 and 15 | Drug | Group 1, Group 2 |
| CisplatinAlso: PlatinolGiven IV, 75 mg/m^2 on day 1 | Drug | Group 1, Group 2 |
Primary outcome
24-month Progression-free Survival
Time frame: assessed within 14 days after delivery of the third cycle of induction therapy, and 8 weeks and 6 months after completion of concurrent therapy, then every 6 months until progression or until 3 years from study entry
24-month progression-free survival is defined as the proportion of patients who were alive and progression-free at 24 months post registration. The primary study population for this endpoint is patients who were confirmed post-induction clinical complete response (CR) at their primary sites and subsequently received 5400 cGy radiation therapy to their primary sites.
2 secondary outcomes
24-months Overall Survival
Time frame: assessed within 14 days after delivery of the third cycle of induction therapy, and 8 weeks and 6 months after completion of concurrent therapy, then every 6 months until progression or until 3 years from study entry
Primary Clinical Response Rate
Time frame: assessed within 14 days after delivery of the third cycle of induction therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28029303Marur S, Li S, Cmelak AJ, Gillison ML, Zhao WJ, Ferris RL, Westra WH, Gilbert J, Bauman JE, Wagner LI, Trevarthen DR, Balkrishna J, Murphy BA, Agrawal N, Colevas AD, Chung CH, Burtness B. E1308: Phase II Trial of Induction Chemotherapy Followed by Reduced-Dose Radiation and Weekly Cetuximab in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx- ECOG-ACRIN Cancer Research Group. J Clin Oncol. 2017 Feb 10;35(5):490-497. doi: 10.1200/JCO.2016.68.3300. Epub 2016 Dec 28.
- Derived from this study: PubMed 25057165Psyrri A, Rampias T, Vermorken JB. The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck. Ann Oncol. 2014 Nov;25(11):2101-2115. doi: 10.1093/annonc/mdu265. Epub 2014 Jul 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shanthi Marur, MD principal investigator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
121 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cetuximab, intensity-modulated radiation therapy (IMRT) and Paclitaxel in people with Head and Neck Cancer and Precancerous Condition, run by Eastern Cooperative Oncology Group at 121 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 121 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24-month Progression-free Survival (time frame: assessed within 14 days after delivery of the third cycle of induction therapy, and 8 weeks and 6 months after completion of concurrent therapy, then every 6 months until progression or until 3 years from study entry). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01084083, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2023.