Individualized Adaptive De-escalated Radiotherapy for HPV-related Oropharynx Cancer

NCT ID: NCT03416153

Last Updated: 2025-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-21
• Study Completion Date: 2025-05-05

Brief Summary

This prospective study aims to utilize pre- and mid-treatment PET-CT to guide de-escalation of radiation therapy in HPV-related squamous cell carcinoma of the oropharynx.

Conditions

Oropharynx Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard Treatment

Patients will receive a single prescription of 70 Gy in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy)

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: DRUG

AUC=1 weekly during radiation therapy. Carboplatin will be given once a week in combination with paclitaxel (standard treatment), concurrent with radiation therapy. Given IV.

Radiation Therapy

Intervention Type: RADIATION

Patients will initially receive a single prescription of 70 Gy to PTV1 in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy). Dose will be reduced to 54Gy to high risk PTV and 43.2Gy to low risk PTV all in 27 fractions for patients who meet pPET-CT and iPET-CT parameters.

Paclitaxel

Intervention Type: DRUG

30 mg/m2 weekly during radiation therapy. Paclitaxel will be given once a week in combination with carboplatin (standard treatment), concurrent with radiation therapy. Given IV.

De-escalation Treatment

Patients will initially receive a single prescription of 70 Gy in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy). If certain parameters are met radiation therapy will be reduced to 54Gy to high risk Planned Target Volume (PTV) and 43.2Gy to low risk PTV all in 27 fractions.

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: DRUG

AUC=1 weekly during radiation therapy. Carboplatin will be given once a week in combination with paclitaxel (standard treatment), concurrent with radiation therapy. Given IV.

Radiation Therapy

Intervention Type: RADIATION

Patients will initially receive a single prescription of 70 Gy to PTV1 in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy). Dose will be reduced to 54Gy to high risk PTV and 43.2Gy to low risk PTV all in 27 fractions for patients who meet pPET-CT and iPET-CT parameters.

Paclitaxel

Intervention Type: DRUG

30 mg/m2 weekly during radiation therapy. Paclitaxel will be given once a week in combination with carboplatin (standard treatment), concurrent with radiation therapy. Given IV.

Interventions

Carboplatin

AUC=1 weekly during radiation therapy. Carboplatin will be given once a week in combination with paclitaxel (standard treatment), concurrent with radiation therapy. Given IV.

Intervention Type: DRUG

Radiation Therapy

Patients will initially receive a single prescription of 70 Gy to PTV1 in 35 fractions with RT given once daily, 5 days a week along with weekly carboplatin and paclitaxel (standard therapy). Dose will be reduced to 54Gy to high risk PTV and 43.2Gy to low risk PTV all in 27 fractions for patients who meet pPET-CT and iPET-CT parameters.

Intervention Type: RADIATION

Paclitaxel

30 mg/m2 weekly during radiation therapy. Paclitaxel will be given once a week in combination with carboplatin (standard treatment), concurrent with radiation therapy. Given IV.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients must have FDG-avid and histologically or cytologically proven squamous cell carcinoma of the oropharynx (tonsil, base of tongue, oropharyngeal wall, soft palate) that is p16 positive by immunohistochemistry or HPV positive by in situ hybridization.
• AJCC eighth edition staging stage 1 and stage 2
• Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
• History/physical examination, including documentation of weight within 4 weeks prior to registration;
• FDG-PET/CT scan for staging and RT plan within 4 weeks prior to registration;
• Zubrod Performance Status (A quantification of the functional status of cancer patients that runs from 0 to 5, with 0 denoting perfect health and 5 death) 0-1 within 4 weeks prior to registration;
• Age ≥ 18;
• Able to tolerate PET/CT imaging required to be performed
• CBC/differential obtained within 4 weeks prior to registration on study, with adequate bone marrow function;
• Serum creatinine within normal institutional limits or a creatinine clearance ≥ 45 ml/min within 4 weeks prior to registration;
• Women of childbearing potential and male participants must agree to use a medically effective means of birth control throughout their participation in the treatment phase of the study.
• The patient must provide study-specific informed consent prior to study entry.

Exclusion Criteria

• cT4, cN3 or cM1 disease
• "Matted nodes" as determined by review with Neuroradiology
• Gross total excision of both primary and nodal disease with curative intent; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. In other words, to participate in this protocol, the patient must have clinically or radiographically evident gross disease for which disease response can be assessed.
• Carcinoma of the neck of unknown primary site origin (even if p16 positive);
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
• Any prior therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable if > 3 years prior to study;
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
• Severe, active co-morbidity;
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception;
• Poorly controlled diabetes

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Ann Arbor Healthcare System

FED

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michelle Mierzwa, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Michigan Rogel Cancer Center

Locations

University of Michigan Hospital

Ann Arbor, Michigan, United States

VA Ann Arbor Healthcare System

Ann Arbor, Michigan, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

HUM00136258

Identifier Type: OTHER

Identifier Source: secondary_id

U01CA183848

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UMCC 2017.113

Identifier Type: -

Identifier Source: org_study_id