Treatment De-Intensification for Squamous Cell Carcinoma of the Oropharynx

NCT01088802 | Completed Phase 2 Results DMC

• 2 other identifiers: J0988NA_00026771
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This research is being done to try to reduce radiation side effects that happen with the standard radiation methods. Generally surgery, radiation therapy, and sometimes chemotherapy are standard treatment for people with squamous cell carcinoma of the oropharynx. The study will look at giving a slightly smaller dose of radiation (de-intensification) to see if regularly expected late toxicities (two years after receiving treatment) can be reduced. This study will also try to see if the smaller dose of radiation is equally effective at treating the cancer and to see if it improves quality of life. Along with this radiation treatment plan some participants in this study will have surgery on their tumor and or receive chemotherapy (cisplatin or carboplatin). The possible surgery and or chemotherapy will be up to the participant's doctor. Study participants will be tested for the Human Papillomavirus (HPV). This tissue test is required for this study. Some studies have suggested that HPV-related cancer is biologically and clinically different as compared to non-HPV-related cancer. Some studies have found that patients with HPV-related oropharynx cancer have a better response to treatment. This test will help researchers learn more about HPV-related cancer.

Conditions

Squamous Cell Carcinoma of Oropharynx

Keywords

Squamous Cell Carcinoma; Oropharynx

Outcome Measures

Primary Outcomes (6)

• Percentage of Patients Free of Grade 3+ Late Toxicity

  The goal is to achieve a prevalence of \< 15% grade 3+ late toxicity at 2 years; reported as percentage of patients who were free of grade 3+ adverse events (AEs) as measured by Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) between 6 months and 24 months. The outcome is reported as percentage of patients who were free of grade 3+ adverse events.

  2 years

• Percentage of Patients With Locoregional Tumor Control

  Locoregional tumor control \> 85 + or - 7% at 2 years; measured through progression-free survival (the time from assignment in a clinical trial to disease progression or death from any cause). Locoregional tumor control is reported as percentage of patients meeting this criteria.

  2 years

• Adverse Events and Their Cause

  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.

  Pretreatment, 3 months, then every 3 months for the first 2 years, then every 6 months for years 3-5

• Quality of Life Measured Through Patient-reported Outcome Measures on Assessments: M.D. Anderson Dysphagia Inventory (MDADI)

  Determine quality of life of surviving patients measured by patient reported outcomes: -MDADI-Self-administered assessment on patient swallowing ability. There are 19 questions specific to swallowing that study patients completed. Composite score is the average of the 19 questions. The scale is 20 (extremely low functioning) to 100 (high functioning). Composite score is reported.

  Baseline, 6-8 weeks, 6 months, 1 year, 2 years, 3 years, 4-5 year visit

• Quality of Life Measured Through Patient-reported Outcome Measures on Assessments: MD Anderson Symptom Inventory-head and Neck Cancer (MDASI-HN)

  Determine quality of life of surviving patients measured by patient reported outcomes: MDASI-HN-Self-reported assessment. Measures symptom severity in previous day. Study patients answered 9 specific questions specific to head and neck cancer. Symptom severity scores, from 0 (not present) to 10 (worst possible). Composite score calculated average of individual scores. Mean module (head and neck) symptom severity is reported.

  Baseline, 6-8 weeks, 1 year, 2 years, 3 years, 4-5 year visit

• Quality of Life Measured Through Patient-reported Outcome Measures on Assessments: Xerostomia Questionnaire (XQ)

  Determine quality of life of surviving patients measured by patient reported outcomes: XQ measures severity of radiation-induced xerostomia and patient reported quality of life. 8 question total:4 on dryness while eating/chewing, 4 on dryness when not eating/chewing. 0-10 (higher scores=severe dryness/discomfort). Composite Scores range from 0 (no xerostomia) -100 (highest level of xerostomia).

  Baseline, 6-8 weeks, 1 year, 2 years, 3 years, 4-5 year visit

Study Arms (1)

Dose de-escalating radiation therapy with chemotherapy

EXPERIMENTAL

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

Radiation: IMRT; Drug: Cisplatin; Drug: Carboplatin

Interventions

IMRT RADIATION

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)

Dose de-escalating radiation therapy with chemotherapy

Cisplatin DRUG

Cisplatin will be administered weekly for the first 3 weeks and the last 3 weeks of radiation. Patients will not receive chemotherapy during week 4 of treatment.

Dose de-escalating radiation therapy with chemotherapy

Carboplatin DRUG

Carboplatin will be administered weekly during the 7 weeks of radiation. Carboplatin may be given as a substitution for cisplatin when cisplatin-related toxicities occur or when patients present with greater than grade 2 sensory or motor neuropathy, greater than 2 hearing loss, or less than 60 ml/min creatinine clearance.

Dose de-escalating radiation therapy with chemotherapy

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy-proven SCC of the oropharynx (tonsil, base of tongue, pharyngeal wall or palate).
• Tumor positive for infection with human papilloma virus (HPV) virus.
• T stage: 1, 2 or T3. 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; pretreatment 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-myelomatous 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.

You may not qualify if:

• Evidence of distant metastases.
• Absence of macroscopic disease after upfront surgery
• 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.
• Patients with greater than 1- pack years of smoking history and/or currently a smoker at the time of treatment

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell

Interventions

Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Harry Quon, MD
• Organization: Johns Hopkins Medicine

hquon2@jhmi.edu

410-502-3877

Study Officials

• Quon Harry, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Arlene Forastiere, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2009
• First Posted: March 17, 2010
• Study Start: March 1, 2010
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: November 8, 2022
• Results First Posted: November 8, 2022

Record last verified: 2022-10

Locations

US (1)