Treatment De-Intensification for Squamous Cell Carcinoma of the Oropharynx - Full Text View

Purpose

The purpose of this study is to examine disease control of contemporary oropharyngeal cancer.

As for many other primary subsites of the head and neck district, two main options have been traditionally employed for the treatment of squamous cell carcinoma of the oropharynx (ORO-SCC), surgery and radiotherapy (RT). The latter has been shown to be less 'invasive' and morbid than radical surgery and therefore has gained consensus as first line option in ORO-SCC at many Institutions across the country.

Surveillance Epidemiology and End Results (SEER) data from 1975 to 2002 show an approximate 5% to 8% improvement in 5-year overall survival for squamous head and neck cancer. Most of this improvement occurred in oropharyngeal carcinoma. Table 1 summarizes results from contemporary series using non-surgical-based approach for ORO-SCC. They consistently show that long-term locoregional control rates are in the order of 80-95%.

Condition	Intervention	Phase
Squamous Cell Carcinoma of Oropharynx	Radiation: IMRT Drug: Cisplatin Drug: Carboplatin	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	A Phase I/II Study on Treatment De-Intensification in Favorable Squamous Cell Carcinoma of the Oropharynx

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Cisplatin Carboplatin

U.S. FDA Resources

Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:

Grade 3+ late toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
To achieve prevalence of grade 3+ late toxicity at 2 years < 15% while maintaining a locoregional tumor control > 85 + or - 7% at the same time interval (toxicity is scored at 5.11 and 9.5 and locoregional and locoregional control at 9.4).
Quality of Life [ Time Frame: Pretreatment, 8 weeks, 3 months, then every 3 months fo rthe first 2 years, then every 6 months for years 3-5 and finally annually ] [ Designated as safety issue: No ]
To determine the quality of life of surviving patients (5.11 and 9.5)
Adverse events and their cause [ Time Frame: Pretreatment, 3 months, then every 3 months for the first 2 years, then every 6 months for years 3-5 and finally annually ] [ Designated as safety issue: Yes ]
To determine the nature and prevalence of side effects at different time intervals and describe their relationship to pretreatment function and local dose and treated volume.

Estimated Enrollment:	60
Study Start Date:	January 2010
Estimated Study Completion Date:	February 2015
Estimated Primary Completion Date:	February 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Dose de-escalating radiation therapy with chemotherapy This protocol combines selective radiation therapy dose de-escalation (from 70 Gy to 63 Gy and from 58.1 Gy to 50.75 Gy, same number of fractions (N=35) in 7 weeks) in patients with HPV-associated cancers of the oropharynx receiving standard of care treatment based on clinical stage.	Radiation: IMRT 70 Gy, 63 Gy and 58.1 Gy to primary tumor and whole neck (PTV1-3) in 35 fractions. The Px to each PTV is reported in table 6. Now we have 4 dose levels, 70, 63, 58.1 and 50.75 Gy. In cases after primary tumor surgery where there is no residual macroscopic disease left, the total dose to PTV1 can be reduced from 70 Gy to 68.25 Gy. In this case PTV68.25 is treated as PTV70 regarding overlap with the various OAR's. Drug: Cisplatin The first dose of cisplatin 40mg/m2 IV will be administered within the first 3 days of the start of RT and repeated weekly for the duration of RT. If RT is held, cisplatin will also be held. Drug: Carboplatin 6.2.4 Switch to Carboplatin: In case of any of the followings, cisplatin will be substituted to carboplatin: serum creatinine above the upper limit of normal and creatinine clearance < 60; refractory magnesium and electrolyte wasting; ototoxicity; peripheral neuropathy grade 2. Weekly carboplatin dosing would be at AUC = 2; q 3wk dosing at AUC = 5.

Arms

Assigned Interventions

Experimental: Dose de-escalating radiation therapy with chemotherapy

This protocol combines selective radiation therapy dose de-escalation (from 70 Gy to 63 Gy and from 58.1 Gy to 50.75 Gy, same number of fractions (N=35) in 7 weeks) in patients with HPV-associated cancers of the oropharynx receiving standard of care treatment based on clinical stage.

Radiation: IMRT

70 Gy, 63 Gy and 58.1 Gy to primary tumor and whole neck (PTV1-3) in 35 fractions. The Px to each PTV is reported in table 6. Now we have 4 dose levels, 70, 63, 58.1 and 50.75 Gy. In cases after primary tumor surgery where there is no residual macroscopic disease left, the total dose to PTV1 can be reduced from 70 Gy to 68.25 Gy. In this case PTV68.25 is treated as PTV70 regarding overlap with the various OAR's.

Drug: Cisplatin

The first dose of cisplatin 40mg/m2 IV will be administered within the first 3 days of the start of RT and repeated weekly for the duration of RT. If RT is held, cisplatin will also be held.

Drug: Carboplatin

6.2.4 Switch to Carboplatin: In case of any of the followings, cisplatin will be substituted to carboplatin: serum creatinine above the upper limit of normal and creatinine clearance < 60; refractory magnesium and electrolyte wasting; ototoxicity; peripheral neuropathy grade 2. Weekly carboplatin dosing would be at AUC = 2; q 3wk dosing at AUC = 5.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Biopsy-proven SCC of the oropharynx (tonsil, base of tongue, pharyngeal wall or palate).
Tumor positive for infection with HPV virus type 16 or other types (section 8.0).
T stage: 1, 2. T3 tumors are allowed if the tumor is arising from the tonsillar fossa and/or is exophytic based on both clinical exam and CT; Surgery of the primary tumor is limited to incisional or excisional biopsies (i.e tonsillectomy) even without macroscopic disease left. Positive resection margins and/or gross residual disease at the primary site are allowed.
Any N stage, but resectable; lymph nodes in both sides of the neck are at risk of metastatic disease, according to clinical judgment, and require irradiation; pre-treatment surgery in the neck in the forms of incisional/excisional biopsy or a multilevel neck dissection is allowed only if there is gross tumor left at the primary site.
No other malignancy except for non-melomatous skin cancer, early stage prostate cancer (T<2a and PSA<10 and GLS<7) or a carcinoma not of head and neck origin disease free for > 5 yrs.
Cannot have distant metastasis (M0)
ECOG performance status 0-1.
Patient's nutritional and general physical condition must be considered compatible with the proposed radiotherapeutic treatment.
Patient is judged to be mentally reliable to follow instructions and to keep appointments.
Patient is on no other treatment for head and neck cancer.
Signed study-specific informed consent prior to registration.

Exclusion Criteria:

Evidence of distant metastases.
Absence of macroscopic disease after upfront surgery, i.e., TxNx and TxN0. TxN+ and T1-3Nx are eligible if the T/N stage categories meet the criteria of 3.1.1.
Previous irradiation for head and neck tumor; concurrent chemotherapy other than the treatment per protocol; previous chemotherapy ≤ 3 months from start of RT.
Active untreated infection.
Major medical or psychiatric illness, which in the investigators' opinions would interfere with either completion of therapy and follow-up or with full and complete understanding of the risks and potential complications of the therapy.
Prophylactic use of amifostine or pilocarpine is not allowed.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01088802

Contacts

Contact: Harry Quon, M.D.	410-502-3877	hquon2@jhmi.edu
Contact: Kelly Szajna	410-502-2942	kszajna1@jhmi.edu

Locations

United States, Maryland
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Recruiting
Baltimore, Maryland, United States, 21231
Principal Investigator: Quon Harry, M.D.
Principal Investigator: Arlene Forastiere, M.D.
Sub-Investigator: Ralph Tufano, M.D.
Sub-Investigator: Christine Gourin, M.D.
Sub-Investigator: Jeremy Richmon, M.D.
Sub-Investigator: Wayne Koch, M.D.
Sub-Investigator: Nafi Aygun, M.D.
Sub-Investigator: William Westra, M.D.
Sub-Investigator: Heather Starmer, MA, CCC-SLP
Sub-Investigator: Kim Webster, MA,MS, CCC-SLP
Sub-Investigator: Donna Tippett, MPH,MA,CCC-SLP
Sub-Investigator: Todd McNutt, PhD
Sub-Investigator: Amanda Blackford, Sc.M.
Sub-Investigator: Mary Griffith, RN
Sub-Investigator: Shirl DiPasquale, RN
Sub-Investigator: Giuseppe Sanguineti, M.D.
Sub-Investigator: Nishant Agrawal, M.D.
Sub-Investigator: Christine Chung, M.D.
Sub-Investigator: Shanthi Marur, M.D.
Sub-Investigator: Moody Wharam, M.D.

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center

Investigators

Principal Investigator:	Quon Harry, M.D.	The Johns Hopkins University School of Medicine
Principal Investigator:	Arlene Forastiere, M.D.	The Johns Hopkins University School of Medicine

More Information

No publications provided

Responsible Party:	Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT01088802 History of Changes
Other Study ID Numbers:	J0988, NA_00026771, NA_00026771
Study First Received:	August 4, 2009
Last Updated:	March 1, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:

Squamous Cell Carcinoma
Oropharynx

Additional relevant MeSH terms:

Carcinoma
Carcinoma, Squamous Cell
Oropharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site

Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Cisplatin
Carboplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 18, 2013