Ph I Vorinostat in the Treatment of Advanced Staged Oropharyngeal Squamous Cell Carcinoma
RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells. Giving vorinostat together with chemotherapy and radiation therapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when given together with cisplatin and radiation therapy in treating patients with stage III or stage IVa squamous cell cancer of the oropharynx which is either unresectable or borderline resectable.
Stage III Squamous Cell Carcinoma of the Oropharynx
Stage IV Squamous Cell Carcinoma of the Oropharynx
Radiation: radiation therapy
Procedure: Correlative Studies
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial Of Vorinostat In The Treatment Of Advanced Laryngeal, Hypopharyngeal, Nasopharyngeal And Oropharyngeal Squamous Cell Carcinoma Of The Head And Neck.|
- Maximum tolerated dose of vorinostat in combination with concurrent chemoradiation therapy [ Time Frame: Weekly during treatment; Every 2 weeks for the first month after treatment completion; Then every 4 weeks until day 153 ] [ Designated as safety issue: Yes ]
- The toxic effects of the combination of vorinostat and cisplatin using NCI CTCAE v. 4.0 [ Time Frame: Weekly during treatment; Every 2 weeks for the first month after treatment completion; Then every 4 weeks until day 153 ] [ Designated as safety issue: Yes ]
- Tumor responses to vorinostat or vorinostat combined with chemoradiation. [ Time Frame: Days 35, 56 then after Day 153 every 12 weeks for 24 months ] [ Designated as safety issue: No ]
- Complete response rate [ Time Frame: Days 35, 56 then after Day 153 every 12 weeks for 24 months ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: Days 35, 56 then after Day 153 every 12 weeks for 24 months ] [ Designated as safety issue: No ]
- Progression free survival [ Time Frame: Days 35, 56 then after Day 153 every 12 weeks for 24 months ] [ Designated as safety issue: No ]
- Relationship between Vorinostat therapy and tumor suppressor genes product assessed by Fas and FasL protein expression level in tumor and the normal mucosa [ Time Frame: Before, post SAHA treatment, and post the concurrent chemoradiation /SAHA therapy ] [ Designated as safety issue: No ]
- HPV-specific T-cell in patients with HPV+ tumors [ Time Frame: After the run in period of vorinostat but before the start of RT; Day 35; 2 weeks after the completion of RT; Day 153 ] [ Designated as safety issue: No ]
|Study Start Date:||February 2010|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive oral vorinostat on days 0-2 and cisplatin IV on days 7, 21 and 35. Patients undergo radiation therapy 5 days a week beginning on day 7. Patients also receive concurrent oral vorinostat along with the radiotherapy to be given 3 days per week (Monday, Tuesday, and Wednesday). Optional repeat tumor and normal mucosal biopsies will be performed and blood will be drawn for correlative studies.
The first vorinostat dose level is 100mg, and the second dose will be 200mg, third dose will be 300mg. If the first vorinostat dose level is found to be excessively toxic, the patient will be reduced to -1 dosing level then if still too toxic reduced again to dose level -2. Dose escalation of vorinostat will continue in increments of 100 mg (i.e., 200 mg on dosing days, 300 mg on dosing days). Vorinostat will be given 3 consecutive days per week (e.g. Monday, Tuesday, Wednesday).
Other Names:Drug: cisplatin
Other Names:Radiation: radiation therapy
Standard chemoradiation therapy X 7 weeks (Days 7-56), concurrent with oral Vorinostat given three days per week (Mon, Tues, Wed)
Other Names:Procedure: Correlative Studies
Day 35, 2 weeks post radiation therapy completion optional tumor/normal muscosal biopsy and blood draw for correlative studies. At day 153 an optional tumor/normal tissue biopsy and blood draw for correlative studies.
I. To determine the maximally tolerated dose of Vorinostat in combination with concurrent chemoradiotherapy for the treatment of advance stage OPSCC.
l. To determine the complete response rate, overall survival and progression free survival using the maximally tolerated dose of Vorinostat.
I. To assess treatment related acute and late toxicities when combining Vorinostat with chemoradiation and correlate these toxicities to molecular markers of apoptosis in tumor and normal oral mucosa.
II. To evaluate the effect of Vorinostat on tumor immune surveillance, particularly in HPV positive patients.
III. To illustrate that Vorinostat alters the methylation status of commonly methylated genes in OPSCC.
OUTLINE: This is a dose-escalation study of vorinostat. Patients receive oral vorinostat on days 0-2 and cisplatin IV on days 7, 21, and 35. Patients undergo radiotherapy 5 days a week beginning on day 7. Patients also receive concurrent oral vorinostat along with the radiotherapy to be given 3 days per week (Monday, Tuesday, and Wednesday). Treatment continues for 7 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01064921
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Theodoros Teknos, MD||Ohio State University|