A Phase 1 interventional study of Hypofractionated intensity modulated radiotherapy in Human Papillomavirus-Related Carcinoma and Oropharyngeal Cancer, sponsored by University of Texas Southwestern Medical Center. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-12-15.
Sponsored by University of Texas Southwestern Medical Center · Phase 1, Interventional, and Treatment
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.
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.
373 studies on the registry are indexed under Oropharyngeal Neoplasms; 97 are open to participants now.
This study's enrollment of 24 is below the median of 48 across 284 interventional studies indexed under Oropharyngeal Neoplasms.
Browse Oropharyngeal Neoplasms studies →University of Texas Southwestern Medical Center is the lead sponsor of 990 studies on the registry; 201 are open to participants now.
Of its 135 completed or terminated interventional studies of FDA-regulated products, 100 (74%) have results posted.
Counted across the registry records on this site, refreshed daily.
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).
Exclusion Criteria:
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)
Maximally Tolerated Dose/Fractionation of Hypofractionated Radiation Therapy
The number of participants experiencing dose-limiting toxicities (DLTs) will be used to determine the maximally tolerated dose (MTD) or optimal fractionation of hypofractionated radiation therapy. Level 0: 46.5 Gy in 15 fractions Level -1: 52 Gy in 20 fractions
Time frame: 3 months
Clinician-reported Acute Toxicities
Toxicities as measured by CTCAE v5.0
Time frame: 0-3 months
Clinician-reported Late Toxicities
As measured by CTCAE v5.0
Time frame: 3-12 months
Percentage of Participants With Locoregional Control
Locoregional control defined as freedom from locoregional recurrence. Locoregional recurrence defined as biopsy-proven viable cancer originating from the primary tumor site (i.e. oropharynx) or a lymph node basin above the clavicles.
Time frame: 12 months
Percentage of Participants With Progression Free Survival
Progression-free survival defined as time from start of treatment to time of progression or death.
Time frame: 1-12 months
Percentage of Participants With Overall Survival
Overall survival defined as time from start of treatment o time of death.
Time frame: 24 months
Swallowing-related Patient-reported Quality of Life
Change from baseline in swallowing-related quality of life, as measured by the MD Anderson Dysphagia Inventory (MDADI) total score, assessed at specified time points (baseline,1, 3, 6, and 12 months) during and after treatment. Higher scores indicate better function, 0-100. Analyses were descriptive, and a paired t test was used to compare questionnaire results over time with P \< .05 considered statistically significant. MDADI composite score difference of 10 was deemed clinically meaningful.
Time frame: 1-12 months
Head and Neck Patient-reported Quality of Life
Change from baseline in head and neck patient-reported outcomes quality of life, as measured by the University of Washington Quality of Life questionnaire (UW-QOL), assessed at specified time points (baseline,1, 3, 6, and 12 months) during and after treatment. Higher scores on UW-QOL subscales indicate better quality of life, 0 being worst and 100 being the best outcome. A paired t test was used to compare questionnaire results over time with P \< .05 considered statistically significant. UW-QOL was divided into 2 subscales of physical and social-emotional function with change of 0.5 x standard deviation (SD) and 0.8 x SD considered moderate and large effect, respectively. Scale title: Patient-reported quality of life at baseline and after treatment (0-100) Physical UW-QOL minimum: 45.83 Physical UW-QOL maximum: 100 Social-Emotional UW-QOL minimum: 17.5 Social-Emotional UW-QOL maximum: 100
Time frame: 1-12 months
General Patient-reported Quality of Life
EuroQol-5 dimensions (EQ-5D-5L): 1-5, higher scores mean worse quality of life. Index score: 0-1, higher scores mean better quality of life. Visual Analog scale: 0-100, higher scores mean better quality of life.
Time frame: 1-12 months
Feeding Tube Dependence
Dependence on tube feeds defined as any participant with daily use of ≥2 nutritional supplements per day via the feeding tube at the time of evaluation.
Time frame: 1-12 months
| Milestone | Dose escalation phase: hypofractionated radiotherapy with cisplatin | Dose expansion phase: hypofractionated radiotherapy with cisplatin |
|---|---|---|
| Started | 6 | 18 |
| Completed | 6 | 18 |
| Not completed | 0 | 0 |
The number of participants experiencing dose-limiting toxicities (DLTs) will be used to determine the maximally tolerated dose (MTD) or optimal fractionation of hypofractionated radiation therapy. Level 0: 46.5 Gy in 15 fractions Level -1: 52 Gy in 20 fractions
| Participants | Hypofractionated radiotherapy with concurrent chemotherapy |
|---|---|
| Maximally Tolerated Dose/Fractionation of Hypofractionated Radiation Therapy | 0 |
Toxicities as measured by CTCAE v5.0
| Participants | Hypofractionated radiotherapy with concurrent chemotherapy (weekly cisplatin 40 mg/m2) |
|---|---|
| Odynophagia/sore throat (grade 2) | 18 |
| Oral mucositis (grade 2) | 15 |
| Weight loss/anorexia (grade 2) | 13 |
| Dysphagia ( grade 2) | 11 |
| Dysgeusia (grade 2) | 9 |
| Xerostomia (grade 2) | 7 |
| Nausea/vomiting (grade 2) | 2 |
| Odynophagia/sore throat (grade 3) | 1 |
| Oral mucositis (grade 3) | 5 |
| Weight loss/anorexia (grade 3) | 2 |
| Dysphagia (grade 3) | 2 |
| Nausea/vomiting (grade 3) | 1 |
As measured by CTCAE v5.0
| Participants | Hypofractionated radiotherapy with concurrent chemotherapy |
|---|---|
| Dysphagia (grade 2) | 1 |
| Weight loss/anorexia (grade 2) | 1 |
| Xerostomia (grade 2) | 1 |
| Grade 3 AE | 0 |
| Grade 4 AE | 0 |
| Grade 5 AE | 0 |
Locoregional control defined as freedom from locoregional recurrence. Locoregional recurrence defined as biopsy-proven viable cancer originating from the primary tumor site (i.e. oropharynx) or a lymph node basin above the clavicles.
| percentage of participants | Hypofractionated radiotherapy with concurrent chemotherapy |
|---|---|
| Percentage of Participants With Locoregional Control | 86.2 (68 to 96.8) |
Progression-free survival defined as time from start of treatment to time of progression or death.
| percentage of participants | Hypofractionated radiotherapy with concurrent chemotherapy |
|---|---|
| Percentage of Participants With Progression Free Survival | 82 (59 to 93) |
Overall survival defined as time from start of treatment o time of death.
| percentage of participants | Hypofractionated radiotherapy with concurrent chemotherapy |
|---|---|
| Percentage of Participants With Overall Survival | 95.8 (74 to 99) |
Change from baseline in swallowing-related quality of life, as measured by the MD Anderson Dysphagia Inventory (MDADI) total score, assessed at specified time points (baseline,1, 3, 6, and 12 months) during and after treatment. Higher scores indicate better function, 0-100. Analyses were descriptive, and a paired t test was used to compare questionnaire results over time with P \< .05 considered statistically significant. MDADI composite score difference of 10 was deemed clinically meaningful.
| score on a scale | Hypofractionated radiotherapy with concurrent chemotherapy |
|---|---|
| Baseline | 86.5 ± 13.7 |
| 1 mo | 77.9 ± 11.6 |
| 3 mo | 85.5 ± 11.3 |
| 6 mo | 87.8 ± 12.3 |
| 12 mo | 89.4 ± 9.4 |
Change from baseline in head and neck patient-reported outcomes quality of life, as measured by the University of Washington Quality of Life questionnaire (UW-QOL), assessed at specified time points (baseline,1, 3, 6, and 12 months) during and after treatment. Higher scores on UW-QOL subscales indicate better quality of life, 0 being worst and 100 being the best outcome. A paired t test was used to compare questionnaire results over time with P \< .05 considered statistically significant. UW-QOL was divided into 2 subscales of physical and social-emotional function with change of 0.5 x standard deviation (SD) and 0.8 x SD considered moderate and large effect, respectively. Scale title: Patient-reported quality of life at baseline and after treatment (0-100) Physical UW-QOL minimum: 45.83 Physical UW-QOL maximum: 100 Social-Emotional UW-QOL minimum: 17.5 Social-Emotional UW-QOL maximum: 100
| score on a scale | Hypofractionated radiotherapy with concurrent chemotherapy |
|---|---|
| Physical Baseline | 93.4 ± 9.9 |
| Physical 1 mo | 74.9 ± 11.4 |
| Physical 3 mo | 80.3 ± 11.3 |
| Physical 6 mo | 84.8 ± 11.7 |
| Physical 12 mo | 85.3 ± 11.7 |
| Social-Emotional Baseline | 89.4 ± 16.5 |
| Social-Emotional 1 mo | 79.9 ± 10.3 |
| Social-Emotional 3 mo | 87.6 ± 10.0 |
| Social-Emotional 6 mo | 90.0 ± 13.8 |
| Social-Emotional 12 mo | 92.1 ± 10.4 |
EuroQol-5 dimensions (EQ-5D-5L): 1-5, higher scores mean worse quality of life. Index score: 0-1, higher scores mean better quality of life. Visual Analog scale: 0-100, higher scores mean better quality of life.
| score on a scale | Hypofractionated radiotherapy with concurrent chemotherapy |
|---|---|
| Index score Enrollment | 0.916 ± 0.163 |
| Index score 1 mo | 0.879 ± 0.107 |
| Index score 3 mo | 0.909 ± 0.120 |
| Index score 6 mo | 0.915 ± 0.166 |
| Index score 12 mo | 0.933 ± 0.103 |
| Visual Analog Scale Enrollment | 86.8 ± 12.4 |
| Visual Analog Scale 1 mo | 79.1 ± 11.5 |
| Visual Analog Scale 3 mo | 81.9 ± 12.0 |
| Visual Analog Scale 6 mo | 86.1 ± 9.8 |
| Visual Analog Scale 12 mo | 88.9 ± 8.0 |
Dependence on tube feeds defined as any participant with daily use of ≥2 nutritional supplements per day via the feeding tube at the time of evaluation.
| participants | Hypofractionated radiotherapy with concurrent chemotherapy |
|---|---|
| Acute follow up period | 2 |
| Late follow up period | 1 |
Collected over 1 year post radiation treatment.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Hypofractionated radiotherapy with concurrent chemotherapy | 1/24 (4.2%) | 6/24 (25%) | 24/24 (100%) |
| Event | Hypofractionated radiotherapy with concurrent chemotherapy |
|---|---|
| Thromboembolic event bilateral pulmonary embolismVascular disorders | 1/24 |
| Death NOSGeneral disorders | 1/24 |
| FeverGeneral disorders | 1/24 |
| Lymphocyte count decreasedInvestigations | 1/24 |
| DysphagiaGastrointestinal disorders | 1/24 |
| Mucositis oralGastrointestinal disorders | 1/24 |
| Event | Hypofractionated radiotherapy with concurrent chemotherapy |
|---|---|
| Dermatitis radiationInjury, poisoning and procedural complications | 24/24 |
| Dry mouthGastrointestinal disorders | 24/24 |
| DysgeusiaNervous system disorders | 24/24 |
| Gastrointestinal disorders - Other, OdynophagiaGastrointestinal disorders | 24/24 |
| DysphagiaGastrointestinal disorders | 23/24 |
| FatigueGeneral disorders | 23/24 |
| Sore throatRespiratory, thoracic and mediastinal disorders | 23/24 |
| Mucositis oralGastrointestinal disorders | 22/24 |
| HypertensionVascular disorders | 19/24 |
| NauseaGastrointestinal disorders | 19/24 |
| Age, Customized(years) | Dose Escalation Phase: Hypofractionated Radiotherapy With Cisplatin | Dose Expansion Phase: Hypofractionated Radiotherapy With Cisplatin | Total |
|---|---|---|---|
| Age (median range) | 59.6 (52 to 72) | 58.9 (50 to 77) | 59.5 (52 to 77) |
| Sex: Female, Male(Participants) | Dose Escalation Phase: Hypofractionated Radiotherapy With Cisplatin | Dose Expansion Phase: Hypofractionated Radiotherapy With Cisplatin | Total |
|---|---|---|---|
| Female | 1 | 0 | 1 |
| Male | 5 | 18 | 23 |
| Race/Ethnicity, Customized(Participants) | Dose Escalation Phase: Hypofractionated Radiotherapy With Cisplatin | Dose Expansion Phase: Hypofractionated Radiotherapy With Cisplatin | Total |
|---|---|---|---|
| Race/ethnicity — White | 4 | 14 | 18 |
| Race/ethnicity — Hispanic | 1 | 0 | 1 |
| Race/ethnicity — African American | 1 | 0 | 1 |
| Race/ethnicity — Asian | 0 | 1 | 1 |
| Race/ethnicity — Other/unknown | 0 | 3 | 3 |
| Region of Enrollment(Participants) | Dose Escalation Phase: Hypofractionated Radiotherapy With Cisplatin | Dose Expansion Phase: Hypofractionated Radiotherapy With Cisplatin | Total |
|---|---|---|---|
| United States | 6 | 18 | 24 |
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University of Texas Southwestern Medical Center