HYHOPE: De-intensified Hypofractionated Radiation Therapy for HPV-associated Oropharynx Cancer

• ClinicalTrials.gov Identifier: NCT04580446
• Recruitment Status: Recruiting
• First Posted: October 8, 2020
• Last Update Posted: January 5, 2022
• Sponsor: University of Texas Southwestern Medical Center
• Collaborator: Gateway for Cancer Research
• Information provided by (Responsible Party): Dominic Moon, University of Texas Southwestern Medical Center

Study Description

Brief Summary:

This is a single arm Phase I study of de-intensified hypofractionated radiation therapy for favorable human papilloma virus-associated oropharynx cancer. It will evaluate the tolerability of a de-intensified hypofractionated radiation therapy regimen completed in 3 weeks (with equivalent biologically effective dose to 60 Gy in 30 fractions) with concurrent weekly cisplatin.

Condition or disease	Intervention/treatment	Phase
Human Papillomavirus-Related Carcinoma; Oropharyngeal Cancer	Radiation: Hypofractionated intensity modulated radiotherapy	Phase 1

Detailed Description:

Standard of care radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC) involves conventional fractionation delivered over a course of 7 weeks. Although hypofractionated RT (HFRT) delivering higher dose of RT each day over a shorter overall treatment time has been studied and adopted as standard of care in many disease sites including breast and prostate cancers, data on HFRT in HNSCC is limited.

There is a strong radiobiological rationale for HFRT for HNSCC to decrease the overall treatment time and thus the effects of accelerated repopulation in this disease entity. In addition, if similar outcomes can be achieved with a reduced number of fractions, cost effectiveness of care can be improved while minimizing the disruption to the patient's personal and professional lives. A substantial decrease in treatment time may improve compliance and financial toxicity associated with the patient's oncologic treatment.

The global COVID-19 pandemic is highlighting the health risk to society at large of having no viable alternative to a 7 week daily RT course for HNSCC, especially in the setting of compromised immune systems associated with concurrent chemotherapy frequently used in this patient population. Thus, the study of HFRT for HNSCC is both timely and potentially paradigm changing for practices across the United States.

The incidence of human papilloma virus (HPV)-associated oropharynx cancer is increasing in the United States, now accounting for 70-80% of all oropharynx cancers. It has a favorable prognosis vs. non-HPV-associated cancers and studies are ongoing to determine the best strategy to de-intensified therapy while maintaining good oncologic outcomes.

The purpose of this single-arm Phase I study is to assess the tolerability and signal for efficacy of de-intensified HFRT for favorable HPV-associated oropharynx cancer. De-intensification will be achieved in two ways. First, the equivalent biologically effective dose (BED) of HFRT used on trial will be 60 Gy of conventionally fractionationated RT (vs. the current standard of care of 70 Gy). Second, the elective nodal volume irradiated will be limited to involved nodal levels and one immediately adjacent level (vs. the current standard of care of entire bilateral neck nodal regions). Patients will complete RT in 15 fractions (3 weeks) with concurrent weekly cisplatin on dose level 0. If a 3-week regimen is not well-tolerated, a 20 fraction regimen will be used on dose level -1.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Rolling 6 dose finding cohort followed by dose expansion cohort
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: HYHOPE: Phase I Study of De-intensified Hypofractionated Radiation Therapy for Human Papilloma Virus-associated Oropharynx Cancer
• Actual Study Start Date: December 17, 2020
• Estimated Primary Completion Date: May 2023
• Estimated Study Completion Date: February 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Hypofractionated radiotherapy with concurrent chemotherapy (weekly cisplatin 40 mg/m2); Level 0: 46.5 Gy in 15 fractions, 5 fractions/week Level -1: 52 Gy in 20 fractions, 5 fractions/week	Radiation: Hypofractionated intensity modulated radiotherapy; Hypofractionated intensity modulated radiotherapy with concurrent chemotherapy (weekly cisplatin)

Outcome Measures

Primary Outcome Measures :

1. Maximally tolerated dose and fractionation of hypofractionated radiation therapy [ Time Frame: 3 months ]

Secondary Outcome Measures :

1. Clinician-reported acute toxicities [ Time Frame: 0-3 months ]
   CTCAE v5.0
2. Clinician-reported late toxicities [ Time Frame: 3-12 months ]
   CTCAE v5.0
3. Locoregional control [ Time Frame: 12 months ]
4. Progression free survival [ Time Frame: 12 months ]
5. Overall survival [ Time Frame: 12 months ]
6. Swallowing-related patient-reported quality of life [ Time Frame: 1-12 months ]
   MD Anderson Dysphagia Inventory (MDADI): 20-100, higher scores mean better quality of life
7. Head and neck patient-reported quality of life [ Time Frame: 1-12 months ]
   University of Washington QOL questionnaire (UW-QOL): 0-100, higher scores mean better quality of life
8. General patient-reported quality of life [ Time Frame: 1-12 months ]
   EuroQol-5 dimensions (EQ-5D-5L): 1-5, higher scores mean worse quality of life
9. Feeding tube dependence [ Time Frame: 1-12 months ]
   Dependence on tube feeds defined as daily use of ≥2 nutritional supplements per day via the feeding tube at the time of evaluation

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Pathologically-proven diagnosis of T1-3 (up to 6 cm), N0-2 (AJCC 8th edition) p16 positive squamous cell carcinoma of the oropharynx (except T1-2N0 as noted in the exclusion criteria)
2. ≤10 pack-year smoking history and not actively smoking
3. Age ≥18 years
4. ECOG performance status 0-2 or Karnofsky Performance Status 50-100

5. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

   A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

6. Negative serum or urine pregnancy test within 2 weeks before registration for women of childbearing potential.
7. Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

1. Distant metastasis
2. T1-2N0 (AJCC 8th edition) p16 positive squamous cell carcinoma of the oropharynx (candidates for definitive RT alone or surgery alone)
3. Inability to receive concurrent weekly cisplatin due to comorbid conditions
4. Synchronous non-skin cancer primaries outside of the oropharynx, oral cavity, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and well-differentiated thyroid cancer. For prostate cancer, patient should not be receiving active treatment. For thyroid cancer, thyroid surgery may occur before or after radiation treatment, provided all other eligibility criteria are met.
5. Prior invasive malignancy with an expected disease-free interval of less than 3 years
6. Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields
7. Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
8. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy agents in this study
9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements
10. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
11. History of severe immunosuppression, including HIV, organ or autologous or allogeneic stem cell transplant, or active immunosuppressive medication at the time of enrollment

Contacts and Locations

Contacts

Contact: Sarah Hardee, MS; 214-645-8525; sarah.hardee@utsouthwestern.edu

Contact: Kajal Desai; 214-645-8525; Kajal.Desai@UTSouthwestern.edu

Locations

United States, Texas

University of Texas Southwestern Medical Center; Recruiting

Dallas, Texas, United States, 75390

Contact: Sarah Hardee, MS 214-645-8525 sarah.hardee@utsouthwestern.edu

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Gateway for Cancer Research

Investigators

• Principal Investigator: Dominic Moon, MD; UT Southwestern Medical Center

More Information

• Responsible Party: Dominic Moon, Principal Investigator, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT04580446
• Other Study ID Numbers: STU 2020-1079
• First Posted: October 8, 2020
• Last Update Posted: January 5, 2022
• Last Verified: December 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Dominic Moon, University of Texas Southwestern Medical Center:

Radiation Dose Hypofractionation

Additional relevant MeSH terms:

Oropharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases