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



Status:Active, not recruiting
Conditions:Cancer, Infectious Disease, Women's Studies
Therapuetic Areas:Immunology / Infectious Diseases, Oncology, Reproductive
Healthy:No
Age Range:18 - Any
Updated:8/3/2018
Start Date:August 2013
End Date:February 2023

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Phase II Randomized Trial of Transoral Surgical Resection Followed by Low-Dose or Standard-Dose IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer

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.

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.

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
We found this trial at
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529 West Markham Street
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1300 Jefferson Park Avenue
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1500 E Duarte Rd
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3300 Gallows Road
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4805 Northeast Glisan Street
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3181 Southwest Sam Jackson Park Road
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6701 N Charles St
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450 Brookline Ave
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10900 Euclid Ave
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2525 S Downing St
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1 Medical Center Dr
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Los Angeles, California 90095
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600 Highland Ave
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9200 W Wisconsin Ave
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Milwaukee, Wisconsin 53295
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New Haven, Connecticut 6520
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8303 Dodge Street
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111 S 11th St
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1235 E Cherokee St
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