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

NCT03416153 | Completed Phase 2 Results DMC FDA Drug FDA Device

• 3 other identifiers: UMCC 2017.113HUM00136258U01CA183848
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (2)

• The Percentage of Patients With Local Regional Recurrence (LRR) of Disease

  RECIST (Response Evaluation Criteria In Solid Tumors) will be used to evaluate response and recurrence. All patients will be analyzed together as the goal of the study is to estimate risk of LRR in this patient population treated with this particular strategy in which some patients continue to receive standard therapy while others are de-escalated. Results will also be estimated and reported separately for patients receiving standard or de-escalated therapy.

  1 Year

• Change in Metabolic Tumor Volume 50% (MTV 50%)

  The change in metabolic tumor volume (MTV)50% at the mid-treatment timepoint will be calculated as percent change from baseline and used as a continuous variable in a Cox model for an outcome of time to LRR. Will also evaluate more non-parametrically, the relation between hazard of LRR and mid-treatment MTV50% using a kernel estimator in a Cox model.

  2 months

Secondary Outcomes (4)

• Quality of Life Assessed Per the Functional Assessment of Cancer Therapy-Head and Neck (FACTHN)

  2 Years

• The Proportion of Patients Alive

  2 Years

• Incidence of Toxicity

  3, 6, 12 and 24 Months

• Detectable Circulating Tumor Deoxyribonucleic Acid (ctDNA) in Participants

  4 weeks

Study Arms (2)

Standard Treatment

ACTIVE COMPARATOR

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)

Drug: Carboplatin; Radiation: Radiation Therapy; Drug: Paclitaxel

De-escalation Treatment

EXPERIMENTAL

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.

Drug: Carboplatin; Radiation: Radiation Therapy; Drug: Paclitaxel

Interventions

Carboplatin 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.

De-escalation Treatment; Standard Treatment

Radiation Therapy 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.

De-escalation Treatment; Standard Treatment

Paclitaxel 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; Standard Treatment

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• VA Ann Arbor Healthcare System: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

Location

VA Ann Arbor Healthcare System

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

Carboplatin; Radiotherapy; Paclitaxel

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Therapeutics; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: University of Michigan Rogel Cancer Center ClinicalTrials.gov Admin
• Organization: University of Michigan Rogel Cancer Center

ClinicalTrialsgov_CCAdmin@umich.edu

734-936-9499

Study Officials

• Michelle Mierzwa, M.D.

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2018
• First Posted: January 30, 2018
• Study Start: May 21, 2018
• Primary Completion: May 5, 2023
• Study Completion: May 5, 2025
• Last Updated: May 22, 2025
• Results First Posted: May 22, 2025

Record last verified: 2025-05

Locations

US (2)