Transoral Surgery Followed By Low-Dose or Standard-Dose Radiation Therapy With or Without Chemotherapy in Treating Patients With HPV Positive Stage III-IVA Oropharyngeal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Eastern Cooperative Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT01898494
First received: July 10, 2013
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

This randomized phase II trial studies how well transoral surgery followed by low-dose or standard-dose radiation therapy works in treating patients with human papilloma virus (HPV) positive stage III-IVA oropharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy with chemotherapy may kill any tumor cells that remain after surgery. It is not yet known how much extra treatment needs to be given after surgery.


Condition Intervention Phase
Human Papilloma Virus Infection
Stage III Squamous Cell Carcinoma of the Oropharynx
Stage IVA Squamous Cell Carcinoma of the Oropharynx
Stage IVB Squamous Cell Carcinoma of the Oropharynx
Procedure: therapeutic conventional surgery
Radiation: intensity-modulated radiation therapy
Drug: cisplatin
Drug: carboplatin
Other: laboratory biomarker analysis
Other: quality-of-life assessment
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Randomized Trial of Transoral Surgical Resection Followed by Low-Dose or Standard-Dose IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • PFS rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Defined as the proportion of patients alive and progression-free at 24 months. Kaplan-Meier estimates will be calculated. 90% exact binomial confidence intervals will be computed for each arm. The 2-year failure proportions that include second primary cancers from the head and neck region as event will also be reported.

  • Accrual rate [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Risk distribution [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
    A 90% binomial confidence interval will be estimated for the percentage of patients in each risk group.

  • Incidence of grade 3-4 bleeding events during surgery and positive margins after surgery, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 [ Time Frame: Up to 18 months ] [ Designated as safety issue: Yes ]
    The percentage will be deemed too high if 13 or more patients reported with grade 3-4 bleeding in the operating room or with positive margins, which corresponds to an empirical rate of 22%. A 90% binomial confidence interval will be estimated for these events.


Secondary Outcome Measures:
  • Incidence of adverse events evaluated by the CTCAE version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    The difference between arms will be evaluated using Fisher's exact test.

  • Overall survival [ Time Frame: Time from registration onto the study until death from any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates will be calculated, along with their corresponding 95% confidence intervals. The median, 1-year, and 2-year survival rates will be estimated.

  • Swallowing function before and after treatment, evaluated using the modified barium swallow (MBS) ratings, performance status scale for head and neck cancer (PSS-HN) normalcy of diet scale, and the MD Anderson Dysphagia Inventory (MDADI) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Descriptive statistics will be provided (by arm) for swallowing function, evaluated using the MBS ratings, PSS-HN normalcy of diet scale, and the validated survey MDADI instrument. Longitudinal analysis will be performed, by arm, on each of these measures.

  • Voice before and after treatment, evaluated using the Voice Handicap Index-10 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Longitudinal analysis will be performed, by arm, on each of these measures.

  • Change in patient reported quality of life (QOL) as measured by Functional Assessment of Cancer Therapy-Head and Neck [ Time Frame: Baseline up to 6 months post radiation therapy ] [ Designated as safety issue: No ]
    Patient QOL will be grouped as "improved" (change >= 7 points, 6 months post-radiation therapy vs. baseline), "worsened" (change =< -7 points) and "stable" (-6 =< change =< 6).


Estimated Enrollment: 377
Study Start Date: August 2013
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (TOS)
Patients undergo transoral surgical resection of the oropharyngeal tumor.
Procedure: therapeutic conventional surgery
Undergo transoral surgical resection
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm B (TOS, low-dose IMRT)
Patients undergo transoral surgical resection of the oropharyngeal tumor. Patients then undergo low-dose IMRT QD five days a week for 5 weeks.
Procedure: therapeutic conventional surgery
Undergo transoral surgical resection
Radiation: intensity-modulated radiation therapy
Undergo low-dose IMRT
Other Name: IMRT
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm C (TOS, standard-dose IMRT)
Patients undergo transoral surgical resection of the oropharyngeal tumor. Patients then undergo standard-dose IMRT QD five days a week for 6 weeks.
Procedure: therapeutic conventional surgery
Undergo transoral surgical resection
Radiation: intensity-modulated radiation therapy
Undergo standard-dose IMRT
Other Name: IMRT
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Experimental: Arm D (TOS, standard-dose IMRT, chemotherapy)
Patients undergo transoral surgical resection of the oropharyngeal tumor. Patients then undergo standard-dose IMRT QD five days a week for 6-7 weeks. Patients also receive cisplatin IV over 60 minutes or carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43 during radiation therapy.
Procedure: therapeutic conventional surgery
Undergo transoral surgical resection
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Radiation: intensity-modulated radiation therapy
Undergo standard-dose IMRT
Other Name: IMRT
Other: laboratory biomarker analysis
Correlative studies
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • REGISTRATION TO SURGERY (ARM S)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Patients must have newly diagnosed, histologically or cytologically confirmed squamous cell carcinoma or undifferentiated carcinoma of the oropharynx; patients must have been determined to have resectable oropharyngeal disease; patients with primary tumor or nodal metastasis fixed to the carotid artery, skull base or cervical spine are not eligible
  • Patients must have American Joint Committee on Cancer (AJCC) TNM tumor stage III, IV a, or IV b (with no evidence of distant metastases) as determined by imaging studies (performed < 4 weeks prior to pre-registration) and complete head and neck exam; the following imaging is required: computed tomography (CT) scan with IV contrast or magnetic resonance imaging (MRI)
  • Patients must have biopsy-proven cyclin-dependent kinase inhibitor 2A (p16)+ oropharynx cancer; the histologic evidence of invasive squamous cell carcinoma may have been obtained from the primary tumor or metastatic lymph node; it is required that patients have nodal stage N1-N2b confirmed by clinical or radiographic methods (clinically N0 patients are not eligible)
  • Carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory; using p16 antibody obtained from Roche mtm laboratories AG (CINtec, clone E6H4) is recommended
  • No prior radiation above the clavicles
  • Patients with a history of a curatively treated malignancy must be disease-free for at least two years except for carcinoma in situ of cervix and/or non-melanomatous skin cancer
  • Patients with the following within the last 6 months prior to pre-registration must be evaluated by a cardiologist and/or neurologist prior to entry into the study
  • Patients must not have evidence of extensive or "matted/fixed" pathologic adenopathy on preoperative imaging
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelets >= 100,000/mm^3
  • Total bilirubin =< the upper limit of normal (ULN)
  • Calculated creatinine clearance must be > 60 ml/min using the Cockcroft-Gault formula
  • Women must not be pregnant or breast-feeding due to the teratogenicity of chemotherapy; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Patient must not have an intercurrent illness likely to interfere with protocol therapy or prevent surgical resection
  • Patients must not have uncontrolled diabetes, uncontrolled infection despite antibiotics or uncontrolled hypertension within 30 days prior to pre-registration
  • REGISTRATION/RANDOMIZATION TO STEP 2 - ARMS A, B, C AND D AND REGISTRATION TO STEP 3
  • Histopathologic assessment of surgical pathology must include examination for perineural invasion (PNI) and lymphovascular invasion (LVI) and reported as absent or present; the absence or presence of extracapsular extension (ECE) requires gross and microscopic assessment and is defined to be:

    • Absent (negative or nodal metastasis with smooth/rounded leading edge confined to thickened capsule/pseudocapsule),
    • Present - minimal (tumor extends =< 1 mm beyond the lymph node capsule), or
    • Present - extensive (gross, tumor extends > 1 mm beyond the lymph node capsule (includes soft tissue metastasis)
  • Patients must have ECOG performance status 0 or 1
  • Patient must be registered/randomized within 5-7 weeks following surgery
  • Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01898494

Locations
United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Michael L. Hinni    507-538-7623      
Principal Investigator: Michael L. Hinni         
United States, California
University of California at Los Angeles (UCLA ) Recruiting
Los Angeles, California, United States, 90095
Contact: Abie H. Mendelsohn    888-798-0719      
Principal Investigator: Abie H. Mendelsohn         
Stanford University Hospitals and Clinics Recruiting
Stanford, California, United States, 94305
Contact: Floyd C. Holsinger    650-498-7061    ccto-office@stanford.edu   
Principal Investigator: Floyd C. Holsinger         
United States, Colorado
Porter Adventist Hospital Recruiting
Denver, Colorado, United States, 80210
Contact: Keren Sturtz    888-785-6789      
Principal Investigator: Keren Sturtz         
United States, Florida
University of Miami Miller School of Medicine-Sylvester Cancer Center Recruiting
Miami, Florida, United States, 33136
Contact: Giovana R. Thomas    866-574-5124    Sylvester@emergingmed.com   
Principal Investigator: Giovana R. Thomas         
Florida Hospital Recruiting
Orlando, Florida, United States, 32803
Contact: Lee M. Zehngebot    407-303-5623      
Principal Investigator: Lee M. Zehngebot         
United States, Kentucky
University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536
Contact: Thomas J. Gal    859-257-3379      
Principal Investigator: Thomas J. Gal         
United States, Maryland
Greater Baltimore Medical Center Recruiting
Baltimore, Maryland, United States, 21204
Contact: Marshall A. Levine    443-849-3706      
Principal Investigator: Marshall A. Levine         
Johns Hopkins University/Sidney Kimmel Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Jeremy D. Richmon    410-955-8804    jhcccro@jhmi.edu   
Principal Investigator: Jeremy D. Richmon         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Tom Thomas    617-724-5200      
Principal Investigator: Tom Thomas         
United States, Missouri
Mercy Hospital Springfield Recruiting
Springfield, Missouri, United States, 65804
Contact: Jay W. Carlson    800-821-7532    sherrijr@iora.org   
Principal Investigator: Jay W. Carlson         
United States, Nebraska
Nebraska Methodist Hospital Recruiting
Omaha, Nebraska, United States, 68114
Contact: Russell B. Smith    402-354-5144      
Principal Investigator: Russell B. Smith         
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: David J. Adelstein    866-223-8100      
Principal Investigator: David J. Adelstein         
Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Enver Ozer    866-627-7616    osu@emergingmed.com   
Principal Investigator: Enver Ozer         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Alison K. Conlin    503-215-6412      
Principal Investigator: Alison K. Conlin         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Miriam N. Lango    215-728-4790      
Principal Investigator: Miriam N. Lango         
University of Pennsylvania/Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Gregory S. Weinstein    800-474-9892      
Principal Investigator: Gregory S. Weinstein         
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Robert L. Ferris    412-647-8073      
Principal Investigator: Robert L. Ferris         
United States, Wisconsin
Froedtert and the Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Stuart J. Wong    414-805-4380      
Principal Investigator: Stuart J. Wong         
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Principal Investigator: Robert Ferris ECOG-ACRIN Cancer Research Group
  More Information

No publications provided

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT01898494     History of Changes
Other Study ID Numbers: E3311, NCI-2013-00814, ECOG-E3311, E3311, E3311, U10CA180820, U10CA021115
Study First Received: July 10, 2013
Last Updated: July 24, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Papilloma
Virus Diseases
Oropharyngeal Neoplasms
Papillomavirus Infections
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
DNA Virus Infections
Tumor Virus Infections
Cisplatin
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 28, 2014