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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

NCT01898494

Description:

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.

Related Conditions:
  • Oropharyngeal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Transoral Surgery Followed By Low-Dose or Standard-Dose <span class="go-doc-concept go-doc-intervention">Radiation</span> Therapy With or Without <span class="go-doc-concept go-doc-intervention">Chemotherapy</span> in Treating Patients With HPV Positive Stage III-IVA Oropharyngeal Cancer

Title

  • Brief Title: 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
  • 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
  • Clinical Trial IDs

    NCT ID: NCT01898494

    ORG ID: E3311

    NCI ID: NCI-2013-00814

    Trial Conditions

    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

    Trial Interventions

    Drug Synonyms Arms
    cisplatin CACP, CDDP, CPDD, DDP Arm D (TOS, standard-dose IMRT, chemotherapy)
    carboplatin Carboplat, CBDCA, JM-8, Paraplat, Paraplatin Arm D (TOS, standard-dose IMRT, chemotherapy)

    Trial 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.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. Accrual, risk distribution, and surgical quality will be used to determine the
    feasibility of a prospective multi-institutional study of transoral surgery for HPV positive
    (+) oropharynx cancer followed by risk-adjusted adjuvant therapy.

    II. To assess the oncologic efficacy following transoral resection and adjuvant therapy in
    patients determined to be at "intermediate risk" after surgical excision, the 2-year
    progression free survival (PFS) rate will be examined.

    SECONDARY OBJECTIVES:

    I. To estimate the patient distribution with various histologic risk features. II. To assess
    and compare early and late toxicities associated with transoral surgery (TOS) and the
    different doses of adjuvant postoperative radiotherapy (PORT).

    III. To evaluate swallowing function before and after TOS and risk-adjusted adjuvant
    therapy.

    IV. To evaluate quality of life (QOL), swallowing perception and performance, voice
    outcomes, and head and neck symptoms.

    TERTIARY OBJECTIVES:

    I. To correlate tumor TP53 mutation and other associated mutation profile with pathologic
    findings, with PFS and other outcome parameters in patients with resectable HPV-associated
    oropharyngeal squamous cell carcinoma (OPSCC) after the above treatments.

    II. To evaluate radiation resistance markers, including excision repair cross complementing
    1 (ERCC1) single nucleotide polymorphism and protein expression, and correlate them with
    treatment efficacy.

    III. To investigate the usefulness of biomarkers in predicting progression-free survival and
    biomarkers, including tumor ERCC1, epidermal growth factor receptor (EGFR), plasma
    cytokine/chemokines, cellular immunity to HPV, and oral HPV deoxyribonucleic acid (DNA).

    OUTLINE: Patients are classified by risk status (low risk, intermediate risk, or high risk)
    and assigned to the appropriate treatment group. Patients classified as intermediate risk
    are randomized to 1 or 2 treatment arms.

    ARM A (low risk): Patients undergo transoral surgical resection of the oropharyngeal tumor.

    ARM B (intermediate risk): Patients undergo transoral surgical resection of the
    oropharyngeal tumor. Patients then undergo low-dose intensity modulated radiation therapy
    (IMRT) once daily (QD) five days a week for 5 weeks.

    ARM C (intermediate risk): Patients undergo transoral surgical resection of the
    oropharyngeal tumor. Patients then undergo standard-dose IMRT QD five days a week for 6
    weeks.

    ARM D (high risk): 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 intravenously (IV) over 60 minutes or carboplatin IV over 30 minutes on
    days 1, 8, 15, 22, 29, 36, and 43 during radiation therapy.

    After completion of study treatment, patients are followed up every 3 months for 2 years and
    then every 6 months for 1 year.

    Trial Arms

    Name Type Description Interventions
    Arm A (TOS) Experimental Patients undergo transoral surgical resection of the oropharyngeal tumor.
    Arm B (TOS, low-dose IMRT) Experimental Patients undergo transoral surgical resection of the oropharyngeal tumor. Patients then undergo low-dose IMRT QD five days a week for 5 weeks.
    Arm C (TOS, standard-dose IMRT) Experimental Patients undergo transoral surgical resection of the oropharyngeal tumor. Patients then undergo standard-dose IMRT QD five days a week for 6 weeks.
    Arm D (TOS, standard-dose IMRT, chemotherapy) Experimental 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. cisplatin, carboplatin

    Eligibility 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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    PFS rate

    Accrual rate

    Risk distribution

    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

    Secondary Outcome Measures

    Incidence of adverse events evaluated by the CTCAE version 4.0

    Overall survival

    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)

    Voice before and after treatment, evaluated using the Voice Handicap Index-10

    Change in patient reported quality of life (QOL) as measured by Functional Assessment of Cancer Therapy-Head and Neck

    Trial Keywords