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Reduced-Dose Intensity-Modulated Radiation Therapy With or Without Cisplatin in Treating Patients With Advanced Oropharyngeal Cancer

NCT02254278

Description:

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.

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Reduced-Dose Intensity-Modulated Radiation Therapy With or Without <span class="go-doc-concept go-doc-intervention">Cisplatin</span> in Treating Patients With Advanced Oropharyngeal Cancer

Title

  • Brief Title: Reduced-Dose Intensity-Modulated Radiation Therapy With or Without Cisplatin in Treating Patients With Advanced Oropharyngeal Cancer
  • Official Title: A Randomized Phase II Trial for Patients With p16 Positive, Non-smoking Associated, Locoregionally Advanced Oropharyngeal Cancer
  • Clinical Trial IDs

    NCT ID: NCT02254278

    ORG ID: NRG-HN002

    NCI ID: NCI-2014-01279

    Trial Conditions

    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

    Trial Interventions

    Drug Synonyms Arms
    Cisplatin Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin Arm I (IMRT, cisplatin)

    Trial Purpose

    This randomized phase II trial studies 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.

    Detailed Description

    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.

    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.

    Trial Arms

    Name Type Description Interventions
    Arm I (IMRT, cisplatin) Experimental Patients undergo IMRT QD five days a week for 6 weeks to a total dose of 60 Gy and receive cisplatin IV over 30-60 minutes weekly during radiation therapy for 6 doses in the absence of disease progression or unacceptable toxicity. Cisplatin
    Arm II (IMRT) Experimental 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.

    Eligibility Criteria

    Inclusion Criteria:

    - 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; however,
    investigators are discouraged from enrolling patients with a history of very
    sustained use of non-cigarette tobacco products alone

    - While there are increased risks of head and neck cancer associated with
    sustained heavy cigar and pipe use, such sustained use of non-cigarette products
    is unusual and does not appear to convey added risk with synchronous cigarette
    smoking

    - 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)

    Exclusion Criteria:

    - 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

    - 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; this includes tonsillectomy,
    local excision of primary site, and nodal excision that removes all clinically and
    radiographically evident disease

    - Simultaneous primary cancers or separate bilateral primary tumor sites

    - 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    PFS

    Secondary Outcome Measures

    Distant metastasis

    Distant metastasis

    HPV DNA copy number

    HPV DNA rate decline

    Human papillomavirus (HPV) deoxyribonucleic acid (DNA) detection rate

    Incidence of acute toxicities (>= grade 3, Common Terminology Criteria for Adverse Events [CTCAE], version [v].4)

    Incidence of acute toxicities (>= grade 3, CTCAE, v.4)

    Incidence of acute toxicities (>= grade 3, CTCAE, v.4)

    Incidence of late toxicities (>= grade 3, CTCAE, v.4)

    Incidence of late toxicities (>= grade 3, CTCAE, v.4)

    Local-regional failure

    Local-regional failure

    Negative predictive value (NPV) of FDG-PET/CT

    Overall survival

    Overall survival

    Patient-reported swallowing outcomes as assessed by the mean individual change in total MDADI score

    Patient-reported swallowing outcomes as assessed by the mean individual change in total MDADI score

    Patient-reported swallowing outcomes as measured by the change in total MDADI score

    Variance for HPV DNA

    Trial Keywords