Description:
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.
Title
- Brief Title: HYHOPE: De-intensified Hypofractionated Radiation Therapy for HPV-associated Oropharynx Cancer
- Official Title: HYHOPE: Phase I Study of De-intensified Hypofractionated Radiation Therapy for Human Papilloma Virus-associated Oropharynx Cancer
Clinical Trial IDs
- ORG STUDY ID:
STU 2020-1079
- NCT ID:
NCT04580446
Conditions
- Human Papillomavirus-Related Carcinoma
- Oropharyngeal Cancer
Purpose
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.
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, and if well tolerated, escalate to
level 1 delivering RT in 12 fractions (3 weeks). If a 3-week regimen is not well-tolerated, a
20 fraction regimen will be used on dose level -1.
Trial Arms
Name | Type | Description | Interventions |
---|
Hypofractionated radiotherapy with concurrent chemotherapy (weekly cisplatin 40 mg/m2) | Experimental | Level 1: 44.4 Gy in 12 fractions, 4 fractions/week
Level 0: 46.5 Gy in 15 fractions, 5 fractions/week
Level -1: 52 Gy in 20 fractions, 5 fractions/week | |
Eligibility 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
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.
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Maximally tolerated dose and fractionation of hypofractionated radiation therapy |
Time Frame: | 3 months |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Clinician-reported acute toxicities |
Time Frame: | 0-3 months |
Safety Issue: | |
Description: | CTCAE v5.0 |
Measure: | Clinician-reported late toxicities |
Time Frame: | 3-12 months |
Safety Issue: | |
Description: | CTCAE v5.0 |
Measure: | Locoregional control |
Time Frame: | 12 months |
Safety Issue: | |
Description: | |
Measure: | Progression free survival |
Time Frame: | 12 months |
Safety Issue: | |
Description: | |
Measure: | Swallowing-related patient-reported quality of life |
Time Frame: | 1-12 months |
Safety Issue: | |
Description: | MD Anderson Dysphagia Inventory (MDADI): 20-100, higher scores mean better quality of life |
Measure: | Head and neck patient-reported quality of life |
Time Frame: | 1-12 months |
Safety Issue: | |
Description: | University of Washington QOL questionnaire (UW-QOL): 0-100, higher scores mean better quality of life |
Measure: | Xerostomia-related patient-reported quality of life |
Time Frame: | 1-12 months |
Safety Issue: | |
Description: | University of Michigan Xerostomia questionnaire (XQ): 0-100, higher scores mean worse quality of life |
Measure: | General patient-reported quality of life |
Time Frame: | 1-12 months |
Safety Issue: | |
Description: | EuroQol-5 dimensions (EQ-5D-5L): 1-5, higher scores mean worse quality of life |
Measure: | Feeding tube dependence |
Time Frame: | 1-12 months |
Safety Issue: | |
Description: | Dependence on tube feeds defined as daily use of ≥2 nutritional supplements per day via the feeding tube at the time of evaluation |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | University of Texas Southwestern Medical Center |
Trial Keywords
- Radiation Dose Hypofractionation
Last Updated
January 7, 2021