De-intensification of Radiation and Chemotherapy for Low-Risk HPV-related Oropharyngeal SCC: Follow-up Study

NCT02281955 | Completed Phase 2 Results DMC

• 1 other identifier: LCCC1413
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Carcinoma, Squamous Cell; Head and Neck Neoplasms; Oropharyngeal Neoplasms

Keywords

Human Papillomavirus; Oropharynx; Oropharyngeal Squamous Cell Carcinoma; Squamous Cell Carcinoma; Radiation Therapy; Chemotherapy; p16

Outcome Measures

Primary Outcomes (1)

• 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.

  Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks)

Secondary Outcomes (5)

• 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)

  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)

  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)

  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)

  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)

  Two years after completion of CRT on last enrolled patient (Note: CRT duration is 6 weeks).

Study Arms (1)

De-escalated Radiation and Chemotherapy

EXPERIMENTAL

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

Interventions

Intensity Modulated Radiotherapy (IMRT) RADIATION

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.

De-escalated Radiation and Chemotherapy

Cisplatin (or alternative) DRUG

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.

De-escalated Radiation and Chemotherapy

Assessment for surgical evaluation PROCEDURE

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.

De-escalated Radiation and Chemotherapy

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age (no upper age limit)
• T0-3, N0 to N2c, M0 squamous cell carcinoma of the oropharynx
• Biopsy proven squamous cell carcinoma that is HPV and/or p16 positive
• ≤ 10 pack-years smoking history or ≤ 30 pack-years smoking history WITH ≥ 5 years abstinence from smoking
• Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to treatment
• ECOG Performance Status 0-1
• CBC/differential obtained within 8 weeks prior to treatment, with adequate bone marrow function defined as follows: Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥ 8.0 g/dl.
• Adequate renal and hepatic function within 4 weeks prior to registration, defined as follows: Serum creatinine \< 2.0 mg/dl; Total bilirubin \< 2 x the institutional ULN; AST or ALT \< 3 x the institutional ULN.
• Negative serum pregnancy test within 2 weeks prior to registration for women of childbearing potential
• Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment and for 6 weeks following treatment.
• Patients must be deemed able to comply with the treatment plan and follow-up schedule.
• Patients must provide study specific informed consent prior to study entry

You may not qualify if:

• Prior history of radiation therapy to the head and neck
• Prior history of head and neck cancer.
• Unresectable disease (e.g. immobile node on physical exam, nodal disease that radiographically involves the carotid arteries, nerves)
• Currently taking Disease Modifying Rheumatoid Drugs (DMRDs)
• Severe, active co-morbidity, defined as follows: Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; Transmural myocardial infarction within the last 6 months; Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration; Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects (Note, however, coagulation parameters are not required for entry into this protocol); Pre-existing ≥ grade 2 neuropathy; Prior organ transplant; Systemic lupus; Psoriatic arthritis.
• Known HIV positive.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead

Study Sites (5)

University of Florida

Gainesville, Florida, 32610, United States

Location

University of North Carolina at Chapel Hill, Department of Radiation Oncology

Chapel Hill, North Carolina, 27599, United States

Location

Pardee Memorial Hospital

Hendersonville, North Carolina, 28791, United States

Location

High Point Regional Health

High Point, North Carolina, 27262, United States

Location

Rex Healthcare

Raleigh, North Carolina, 27607, United States

Location

Related Publications (2)

• Chera BS, Kumar S, Shen C, Amdur R, Dagan R, Green R, Goldman E, Weiss J, Grilley-Olson J, Patel S, Zanation A, Hackman T, Blumberg J, Patel S, Thorp B, Weissler M, Yarbrough W, Sheets N, Mendenhall W, Tan XM, Gupta GP. Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer. J Clin Oncol. 2020 Apr 1;38(10):1050-1058. doi: 10.1200/JCO.19.02444. Epub 2020 Feb 4.

  PMID: 32017652 DERIVED

• Chera BS, Amdur RJ, Green R, Shen C, Gupta G, Tan X, Knowles M, Fried D, Hayes N, Weiss J, Grilley-Olson J, Patel S, Zanation A, Hackman T, Zevallos J, Blumberg J, Patel S, Kasibhatla M, Sheets N, Weissler M, Yarbrough W, Mendenhall W. Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma. J Clin Oncol. 2019 Oct 10;37(29):2661-2669. doi: 10.1200/JCO.19.01007. Epub 2019 Aug 14.

  PMID: 31411949 DERIVED

MeSH Terms

Conditions

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

Interventions

Radiotherapy, Intensity-Modulated; Cisplatin; Restraint, Physical

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Behavior Control; Immobilization; Investigative Techniques

Results Point of Contact

• Title: Dr. Colette Shen
• Organization: University of North Carolina at Chapel Hill

cjshen@email.unc.edu

984-974-0400

Study Officials

• Colette Shen, MD

  University of North Carolina at Chapel Hill, Department of Radiation Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: October 3, 2014
• First Posted: November 4, 2014
• Study Start: August 1, 2014
• Primary Completion: November 1, 2019
• Study Completion: November 24, 2024
• Last Updated: January 7, 2025
• Results First Posted: December 22, 2020

Record last verified: 2024-12

Locations

US (5)