A Phase 2 interventional study of Intensity Modulated Radiotherapy (IMRT) and Cisplatin (or alternative) in Carcinoma, Squamous Cell, Head and Neck Neoplasms and Oropharyngeal Neoplasms, sponsored by UNC Lineberger Comprehensive Cancer Center. Completed at 5 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-01-07.
Sponsored by UNC Lineberger Comprehensive Cancer Center · Phase 2, Interventional, and Treatment
The purpose of this research study is to learn about the effectiveness of using lower-intensity radiation and chemotherapy to treat human papillomavirus (HPV) associated low-risk oropharyngeal and/or unknown primary squamous cell carcinomas of the head and neck. The cure rate for this type of cancer is estimated to be high, > 90%. The standard treatment for this cancer is 7 weeks of radiation with 3 high doses of cisplatin. Sometimes surgery is performed afterwards. This standard regimen causes a lot of side effects and long term complications. This study is evaluating whether a lower dose of radiation and chemotherapy may provide a similar cure rate as the longer, more intensive standard regimen. Patients in this study will receive 1 less week of radiation and a lower weekly dose of chemotherapy.
The proposed study is a follow-up study to NCT01530997. In NCT01530997, patients with HPV positive and/or p16 positive low-risk oropharyngeal squamous cell carcinoma (OPSCC) received de-intensified chemoradiotherapy (CRT) followed by a limited surgical evaluation. The primary endpoint of NCT01530997 was the rate of pathological complete response (pCR) after CRT. Power computations were performed for N=40 and were based on the null hypothesis (H0) that the pCR for de-intensified chemoradiotherapy is at least 87%, the historical rate. The type 1 error for this calculation was 14.2%. 43 patients enrolled and 38 were evaluable for the primary endpoint. The observed pCR rate was 89% (34/38). Since the observed pCR rate was excellent in NCT01530997 and was in concordance with the expected rate, in the proposed study we will not mandate a post-CRT surgical evaluation. Instead a PET/CT 10 to 16 weeks post-CRT will be used to determine whether a surgical evaluation is needed.
6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.
This study's enrollment of 115 is above the median of 45 across 5,170 interventional studies indexed under Carcinoma.
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Of its 32 completed or terminated interventional studies of FDA-regulated products, 25 (78%) have results posted.
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Exclusion Criteria:
Patients will receive Intensity Modulated Radiotherapy Treatments (IMRT), 60 Gy at 2 Gy/fx. The acceptable weekly chemotherapy regimens are Cisplatin 30 to 40 mg/m2 (first choice), Cetuximab 250mg/m2 (second choice), Carboplatin AUC 1.5 and paclitaxel 45 mg/m2 (third choice), Carboplatin AUC 3 (fourth choice). Chemotherapy will be given intravenously weekly during IMRT, 6 total doses. Chemotherapy will not be given to patients with T0-2 N0-1 disease, ≤ 10 pack years smoking history. Decision for surgical evaluation will be based on the results of the PET/CT and clinical exam 10-16 weeks after CRT. Patients with a positive PET/CT scan will undergo surgical evaluation at the discretion of the surgeon. Patients with a negative PET/CT scan will be observed.
Radiation: Intensity Modulated Radiotherapy (IMRT) · Drug: Cisplatin (or alternative) · Procedure: Assessment for surgical evaluation
All patients will receive Intensity Modulated Radiotherapy Treatments (IMRT). Dose painting IMRT will be used and all doses will be specified to the planning target volume (PTV). The high risk planning target volume (PTV-HR) and standard risk planning target volume (PTV-SR) will be treated to the following respective total doses: 60 Gy and 54 Gy. The dose per fraction to the PTV-HR and PTV-SR will be 2 Gy per day and 1.8 Gy per day respectively. The PTV-HR will include the gross tumor and the PTV-SR will include areas at risk for harboring subclinical microscopic disease.
Cisplatin is the preferred mandated first choice chemotherapy, however alternative weekly regimens are permissible. Justification for not using cisplatin must be documented. Chemotherapy will be given intravenously weekly during IMRT. 6 total doses will be given. It is preferred that the doses be administered on days 1, 8, 15, 22, 29, and 36; however, this is not mandatory. Chemotherapy will not be given to patients with T0-2 N0-1 disease, ≤ 10 pack years smoking history.
Decisions for surgical evaluation will be based on the results of the PET/CT 10 to 16 weeks after CRT and clinical exam (including fiberoptic laryngoscopy) at that time. Other optional imaging studies may be performed. Patients with a positive PET/CT scan will undergo surgical evaluation at the discretion of the surgeon, with the goal being to remove any suspected residual tumor with a negative resection margin while maintaining organ preservation. This may include biopsies and/or oncological resections of the primary tumor and lymph node metastases. Patients with a negative PET/CT scan will be observed.
2 Year Progression Free Survival After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
Progression Free Survival (PFS) was defined as the time from the beginning of treatment to cancer progression or death. The outcome measure will be reported as the proportion of patients with PFS at 2 years post-treatment.
Time frame: Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks)
2 Year Local Control (LC) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
The outcome measure will be reported as the proportion of patients with LC at 2 years post-treatment.
Time frame: Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).
2 Year Regional Control (RC) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
The outcome measure will be reported as the proportion of patients with RC at 2 years post-treatment.
Time frame: Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).
2 Year Local-regional Control (LRC) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
The outcome measure will be reported as the proportion of patients with LRC at 2 years post-treatment.
Time frame: Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).
2 Year Distant Metastasis Free Survival (DMFS) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
The outcome measure will be reported as the proportion of patients with DMFS at 2 years post-treatment.
Time frame: Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).
2 Year Overall Survival (OS) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC)
The outcome measure will be reported as the proportion of patients who are still alive (overall survival) at 2 years post-treatment.
Time frame: Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).
Enrolling institutions included University of North Carolina Hospitals (Chapel Hill, NC), University of Florida Hospitals (Gainesville, FL), Rex Hospital (Raleigh, NC), High Point Regional Health (High Point, NC), and Pardee Memorial Hospital (Hendersonville, NC).
| Milestone | De-escalated Radiation and Chemotherapy |
|---|---|
| Started | 114 |
| Completed | 113 |
| Not completed | 1 |
| Withdrew: Death | 1 |
Progression Free Survival (PFS) was defined as the time from the beginning of treatment to cancer progression or death. The outcome measure will be reported as the proportion of patients with PFS at 2 years post-treatment.
| Participants | De-escalated Radiation and Chemotherapy |
|---|---|
| 2 Year Progression Free Survival After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC) | 99 |
The outcome measure will be reported as the proportion of patients with LC at 2 years post-treatment.
| Participants | De-escalated Radiation and Chemotherapy |
|---|---|
| 2 Year Local Control (LC) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC) | 107 |
The outcome measure will be reported as the proportion of patients with RC at 2 years post-treatment.
| Participants | De-escalated Radiation and Chemotherapy |
|---|---|
| 2 Year Regional Control (RC) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC) | 110 |
The outcome measure will be reported as the proportion of patients with LRC at 2 years post-treatment.
| Participants | De-escalated Radiation and Chemotherapy |
|---|---|
| 2 Year Local-regional Control (LRC) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC) | 105 |
The outcome measure will be reported as the proportion of patients with DMFS at 2 years post-treatment.
| Participants | De-escalated Radiation and Chemotherapy |
|---|---|
| 2 Year Distant Metastasis Free Survival (DMFS) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC) | 103 |
The outcome measure will be reported as the proportion of patients who are still alive (overall survival) at 2 years post-treatment.
| Participants | De-escalated Radiation and Chemotherapy |
|---|---|
| 2 Year Overall Survival (OS) Rate After De-intensified Chemoradiotherapy (CRT) in Human Papilloma Virus (HPV)-Positive and/or p16 Positive Low-risk Oropharyngeal Squamous Cell Carcinoma (OPSCC) | 106 |
Collected over 2 years post-treatment. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| De-escalated Radiation and Chemotherapy | 5/114 (4.4%) | 0/114 (0%) | 59/114 (51.8%) |
| Event | De-escalated Radiation and Chemotherapy |
|---|---|
| Pharyngeal mucositisRespiratory, thoracic and mediastinal disorders | 28/114 |
| AnorexiaMetabolism and nutrition disorders | 26/114 |
| DysphagiaGastrointestinal disorders | 25/114 |
| Mucositis oralGastrointestinal disorders | 21/114 |
| PainGeneral disorders | 15/114 |
| NauseaGastrointestinal disorders | 11/114 |
| DehydrationMetabolism and nutrition disorders | 5/114 |
| FatigueGeneral disorders | 5/114 |
| VomitingGastrointestinal disorders | 4/114 |
| AnxietyPsychiatric disorders | 3/114 |
| Age, Continuous(years) | De-escalated Radiation and Chemotherapy |
|---|---|
| Mean | 62 (37 to 87) |
| Sex: Female, Male(Participants) | De-escalated Radiation and Chemotherapy |
|---|---|
| Female | 18 |
| Male | 96 |
| Race (NIH/OMB)(Participants) | De-escalated Radiation and Chemotherapy |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 7 |
| White | 104 |
| More than one race | 0 |
| Unknown or Not Reported | 3 |
| Region of Enrollment(participants) | De-escalated Radiation and Chemotherapy |
|---|---|
| United States | 114 |
| Marital Status(Participants) | De-escalated Radiation and Chemotherapy |
|---|---|
| Married | 90 |
| Unmarried | 23 |
| Unknown | 1 |
| Tobacco Use(Participants) | De-escalated Radiation and Chemotherapy |
|---|---|
| Never smoked | 54 |
| <= 10 pack-years | 38 |
| > 10 pack-years | 22 |
| Primary Tumor Location(Participants) | De-escalated Radiation and Chemotherapy |
|---|---|
| Tonsil | 52 |
| Base of tongue | 57 |
| Unknown primary | 5 |
| T Stage(Participants) | De-escalated Radiation and Chemotherapy |
|---|---|
| T0 | 5 |
| T1 | 35 |
| T2 | 61 |
| T3 | 13 |
3 further baseline measures are reported on the registry.
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