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Summary

for people ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started

Description

Summary

This randomized phase II trial studies the side effects and how well modestly reduced-dose intensity-modulated radiation therapy (IMRT) with or without cisplatin works in treating patients with oropharyngeal cancer that has spread to other places in the body (advanced). Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether IMRT is more effective with or without cisplatin in treating patients with oropharyngeal cancer.

Official Title

A Randomized Phase II Trial for Patients With p16 Positive, Non-Smoking Associated, Locoregionally Advanced Oropharyngeal Cancer

Details

PRIMARY OBJECTIVES:

I. To select the arm(s) achieving a 2-year progression-free survival rate of>= 85% without unacceptable swallowing toxicity at 1 year.

SECONDARY OBJECTIVES:

I. To determine patterns of failure (locoregional relapse versus distant) and survival (overall and progression-free) at 6 months and 2 years.

II. To determine acute toxicity profiles at the end of radiation therapy and at 1 and 6 months.

III. To determine late toxicity profiles at 1 and 2 years. IV. To determine patient-reported swallowing outcomes at 6 months and 1 and 2 years.

V. To determine the predictive value of 12-14 week, post-treatment fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) for locoregional control and progression free survival (PFS) at 2 years.

VI. To determine the predictive value of blood and tissue biomarkers for disease outcomes at 2 years.

VII. To determine swallowing recovery per videofluoroscopy imaging at 2 years.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo IMRT once daily (QD) five days a week for 6 weeks to a total dose of 60 Gy and receive cisplatin intravenously (IV) over 30-60 minutes weekly during radiation therapy for 6 doses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo IMRT five days a week for 5 weeks to a total dose of 60 Gy in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Keywords

Stage III Oropharyngeal Squamous Cell Carcinoma Stage IVA Oropharyngeal Squamous Cell Carcinoma Stage IVB Oropharyngeal Squamous Cell Carcinoma Stage IVC Oropharyngeal Squamous Cell Carcinoma Tongue Carcinoma Cisplatin

Eligibility

You can join if…

Open to people ages 18 years and up

  • STEP 1: REGISTRATION
  • Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma) of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls); cytologic diagnosis from a cervical lymph node is sufficient in the presence of clinical evidence of a primary tumor in the oropharynx;clinical evidence should be documented, may consist of palpation, imaging, or endoscopic evaluation, and should be sufficient to estimate the size of the primary(for T stage)
  • Patients must have clinically or radiographically evident measurable disease at the primary site or at nodal stations; tonsillectomy or local excision of the primary without removal of nodal disease is permitted, as is excision removing gross nodal disease but with intact primary site; limited neck dissections retrieving =< 4 nodes are permitted and considered as non-therapeutic nodal excisions
  • Immunohistochemical staining for p16 must be performed on tissue, and this tissue must be submitted for central review; fine needle aspiration (FNA) biopsy specimens may be used as the sole diagnostic tissue if formalin-fixed paraffin-embedded cell block material is available for p16 immunohistochemistry; FNA specimens prepared with adequate p16 testing in this manner are acceptable to submit for central review; if the p16 preparation is not adequate, additional specimens will be required to establish p16 status; centers are encouraged to contact the pathology chairs for clarification
  • Clinical stage T1-T2, N1-N2b or T3, N0-N2b (American Joint Committee on Cancer [AJCC],7th edition [ed.]) including no distant metastases based on the following diagnostic workup:
  • General history and physical examination within 56 days prior to registration
  • Fiberoptic exam with laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) within 70 days prior to registration
  • One of the following combinations of imaging is required within 56 days prior to registration:
  • A CT scan of the neck (with contrast) and a chest CT scan (with or without contrast)
  • Or a magnetic resonance imaging (MRI) of the neck (with contrast) and a chest CT scan (with or without contrast)
  • Or a CT scan of neck (with contrast) and a PET/CT of neck and chest (with or without contrast)
  • Or an MRI of the neck (with contrast) and a PET/CT of neck and chest (with or without contrast)
  • Note: a CT scan of neck and/or a PET/CT performed for the purpose of radiation planning may serve as both staging and planning tools
  • Patients must provide their personal smoking history prior to registration; the lifetime cumulative history cannot exceed 10 pack-years; the following formula is used to calculate the pack-years during the periods of smoking in the patient's life; the cumulative total of the number of pack-years during each period of active smoking is the lifetime cumulative history
  • Number of pack-years = (frequency of smoking [number of cigarettes per day] x duration of cigarette smoking [years])/20
  • Note: twenty cigarettes is considered equivalent to one pack; the effect of non-cigarette tobacco products on the survival of patients with p16-positive oropharyngeal cancers is undefined; cigar and pipe tobacco consumption is therefore not included in calculating the lifetime pack-years; marijuana consumption is likewise not considered in this calculation; there is no clear scientific evidence regarding the role of chewing tobacco-containing products in this disease; investigators are discouraged from enrolling patients with a history of very sustained use (such as several years or more) of non-cigarette tobacco products alone
  • Zubrod performance status of 0-1 within 56 days prior to registration
  • Absolute neutrophil count (ANC)>= 1,500 cells/mm^3
  • Platelets>= 100,000 cells/mm^3
  • Hemoglobin>= 8.0 g/dl; Note: the use of transfusion or other intervention to achieve hemoglobin (Hgb)>= 8.0 g/dl is acceptable
  • Serum creatinine =< 1.5 mg/dl or creatinine clearance (CC)>= 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula
  • Bilirubin =< 2 mg/dl
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x the upper limit of normal
  • Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential
  • Patients who are human immunodeficiency virus (HIV) positive but have no prior acquired immune deficiency syndrome (AIDS)-defining illness and have cluster of differentiation (CD)4 cells of at least 350/mm^3 are eligible; HIV-positive patients must not have multi-drug resistant HIV infection or other concurrent AIDS-defining conditions; patients must not be seropositive for hepatitis B (hepatitis B surface antigen positive or anti-hepatitis B core antigen positive) or seropositive for hepatitis C (anti-hepatitis C antibody positive); however, patients who are immune to hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B)
  • The patient must provide study-specific informed consent prior to study entry,including consent for mandatory submission of tissue for required, central p16 review
  • Patients who speak English (or read one of the languages for which a translation is available must consent to complete the mandatory dysphagia-related patient reported instrument (MDADI); if the patient cannot understand spoken English and reads only languages not available in the MDADI translations, the patient can still participate in the trial, as this has been factored into the trial statistics; for all other patients, the MDADI is mandatory as it is included in the primary endpoint to be studied
  • STEP 2: RANDOMIZATION
  • p16 positive by immunohistochemistry (defined as greater than 70% strong nuclear or nuclear and cytoplasmic staining of tumor cells, confirmed by central pathology review)

You CAN'T join if...

  • STEP 1 (REGISTRATION)
  • Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16 positive, or histologies of adenosquamous, verrucous, or spindle cell carcinomas
  • Carcinoma of the neck of unknown primary site origin (even if p16 positive)
  • Radiographically matted nodes, defined as 3 abutting nodes with loss of the intervening fat plane
  • Supraclavicular nodes, defined as nodes visualized on the same axial imaging slice as the clavicle
  • Definitive clinical or radiologic evidence of metastatic disease or adenopathy below the clavicles
  • Gross total excision of both primary and nodal disease with curative intent; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease; in other words, to participate in this protocol, the patient must have clinically or radiographically evident gross disease for which disease response can be assessed
  • Patients with simultaneous primary cancers or separate bilateral primary tumor sites are excluded with the exception of patients with bilateral tonsil cancers
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast,oral cavity, or cervix are all permissible)
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
  • Severe, active co-morbidity defined as follows:
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol other than those requested
  • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients
  • Pregnancy
  • Prior allergic reaction to cisplatin

Locations

  • Kaiser Permanente Cancer Treatment Center
    South San Francisco, California, 94080, United States
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley, California, 94704, United States
  • Marin General Hospital
    Greenbrae, California, 94904, United States
  • Mills - Peninsula Hospitals
    Burlingame, California, 94010, United States
  • Kaiser Permanente Oakland-Broadway
    Oakland, California, 94611, United States
  • John Muir Medical Center-Walnut Creek
    Walnut Creek, California, 94598, United States
  • Palo Alto Medical Foundation Health Care
    Palo Alto, California, 94301, United States
  • Stanford Cancer Institute
    Palo Alto, California, 94304, United States
  • Palo Alto Medical Foundation-Sunnyvale
    Sunnyvale, California, 94086, United States
  • Kaiser Permanente Medical Center - Santa Clara
    Santa Clara, California, 95051, United States
  • Rohnert Park Cancer Center
    Rohnert Park, California, 94928, United States
  • Stanford Cancer Center South Bay
    San Jose, California, 95124, United States
  • Saint Helena Hospital
    Saint Helena, California, 94574, United States
  • South Sacramento Cancer Center
    Sacramento, California, 95823, United States
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California, 95817, United States
  • Sutter General Hospital
    Sacramento, California, 95816, United States
  • Memorial Medical Center
    Modesto, California, 95355, United States
  • Kaiser Permanente-Rancho Cordova Cancer Center
    Rancho Cordova, California, 95670, United States
  • The Permanente Medical Group-Roseville Radiation Oncology
    Roseville, California, 95678, United States
  • Sutter Cancer Centers Radiation Oncology Services-Roseville
    Roseville, California, 95661, United States
  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    Cameron Park, California, 95682, United States
  • Tahoe Forest Cancer Center
    Truckee, California, 96161, United States
  • Saint Mary's Regional Medical Center
    Reno, Nevada, 89503, United States
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California, 90027, United States
  • City of Hope South Pasadena
    South Pasadena, California, 91030, United States
  • City of Hope Comprehensive Cancer Center
    Duarte, California, 91010, United States
  • UC Irvine Health/Chao Family Comprehensive Cancer Center
    Orange, California, 92868, United States
  • Radiation Oncology Centers of Nevada Central
    Las Vegas, Nevada, 89106, United States

Details

Status
in progress, not accepting new patients
Start Date
Sponsor
NRG Oncology
ID
NCT02254278
Phase
Phase 2
Lead Scientist
Sue Yom
Study Type
Interventional
Last Updated
March 1, 2017