Clinical Trials Search

Title   Phase II Randomized Trial of Transoral Surgical Resection Followed by Low-dose or Standard-dose IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer
Study Number   E3311
Trial Type   Oncology-Head and Neck
Condition   Oropharynx
Trial Status   Open to Accrual
Principal Investigator   Marshall Levine¬ł MD
Contact¬†Name   Brendan Costello
Phone   (443) 849-3122
Description  

 

BRIEF SUMMARY:

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 positive stage III-IVA oral 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 OBJECTIVE:

I. Accrual, risk distribution, and surgical quality will be used to determine the feasability of a prospective multi-institutional study of transoral surgery for human papilloma virus positive (HPV+) 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.

INTERVENTION:

- Procedure: therapeutic conventional surgery

  Undergo transoral surgical resection

- Radiation: intensity-modulated radiation therapy

  Undergo low-dose IMRT (Other Name: IMRT)

- 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

- Procedure: quality-of-life assessment, Ancillary studies

  Other Name: quality of life assessment

 

STUDY ARMS:

- Experimental: Arm A (TOS)

Patients undergo transoral surgical resection of the oropharyngeal tumor.

Interventions: Procedure: therapeutic conventional surgery

Other: laboratory biomarker analysis

Procedure: 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.

Interventions: Procedure: therapeutic conventional surgery

Radiation: intensity-modulated radiation therapy

Other: laboratory biomarker analysis

Procedure: 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.

Interventions: Procedure: therapeutic conventional surgery

Radiation: intensity-modulated radiation therapy

Other: laboratory biomarker analysis

Procedure: 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 30 minutes or carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43 during radiation therapy.

Interventions: Procedure: therapeutic conventional surgery

Drug: cisplatin

Drug: carboplatin

Radiation: intensity-modulated radiation therapy

Other: laboratory biomarker analysis

Procedure: quality-of-life assessment

 

 

 

Inclusion/Notes  

 

INCLUSION CRITERIA

-  REGISTRATION TO SURGERY (ARM S)

-  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

-  Must be 18 years or older

-  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)

-  Primary: patients must have measurable disease of the primary by both clinical and radiographic methods; to meet this criteria, a lesion must be > 2 cm in at least one dimension by clinical exam AND by radiographic exam with CT or MRI; if radiographic exam utilizes spiral CT, lesion must be > 1cm in at least one dimension; Nodes: although it is required that patients must have nodal stage beyond N0 confirmed by clinical or radiographic methods, measurable nodal disease is not required

-  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: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) 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 spread (ECS) 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

 

 

Greater Baltimore Medical Center | 6701 North Charles Street | Baltimore, MD 21204 | (443) 849-2000 | TTY (800) 735-2258
© 2014  GBMC. This website is for informational purposes only and not intended as medical advice or a substitute for a consultation with a professional healthcare provider.