PET-MRI Assessment of Early Tumor Response to Predict Outcomes of HPV-Positive Oropharynx Cancer Patients

NCT03342378 | Completed DMC FDA Drug

• 4 other identifiers: UW170782017-1010P50DE026787Protocol Version 1/7/2020
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This proposal explores the novel hypothesis that the variability in outcomes within the Intermediate Risk(IR) HPV-positive Oropharynx Squamous Cell Carcinoma(OPSCC) cohort can be exploited to identify a subpopulation that exhibits outcomes similar to Low Risk (LR) HPV-positive Oropharynx Squamous Cell Carcinoma and therefore would be appropriate candidates for radiation dose de-escalation approaches. Current literature using PET, CT, and MRI as single imaging modalities have identified certain criteria within heterogenous patient populations that are associated with clinical outcomes. Here, the investigators will test the hypothesis that multiparametric analysis of simultaneously-acquired MRI and PET quantitative imaging biomarker data from the primary tumor prior to initiating therapy, after 2 weeks of chemoradiation(CRT), and 3 months following completion of chemoradiation in patients with Intermediate Risk HPV-positive Oropharynx Squamous Cell Carcinoma will generate parametric maps that are predictive of clinical outcome. Furthermore, the investigators will collect blood samples prior to, during, and after radiation therapy to evaluate whether levels of detected circulating tumor cells correlate with response to treatment.

Conditions

Squamous Cell Carcinoma; Oropharynx Cancer

Keywords

HPV; HPV-positive; Oropharynx Cancer

Outcome Measures

Primary Outcomes (2)

• Radiographic change in the primary tumor of patients with LR and IR HPV-positive OPSCC using MRI/PET imaging

  Patients with LR and IR HPV-positive OPSCC will be segregated into favorable and unfavourable cohorts using radiographic change(MRI/PET) in the primary tumor between pre-treatment and intra-treatment. T-stage, N-stage, and pack-years smoking markers will be used as surrogate markers

  Pre-treatment (baseline) and following 2-weeks of CRT (approximately 2-3 weeks on study)

• Radiographic change in the primary largest pathologic lymph node of patients with LR and IR HPV-positive OPSCC using MRI/PET imaging

  Patients with LR and IR HPV-positive OPSCC will be segregated into favorable and unfavourable cohorts using radiographic change(MRI/PET) in the largest pathologic lymph node between pre-treatment and intra-treatment. T-stage, N-stage, and pack-years smoking markers will be used as surrogate markers

  Pre-treatment (baseline) and following 2-weeks of CRT (approximately 2-3 weeks on study)

Secondary Outcomes (7)

• Progression Free Survival

  up to 2 years

• Absolute volumetric change of the primary tumor

  Following 2-weeks of CRT (approximately 2-3 weeks on study)

• Absolute metabolic change of the primary tumor

  Following 2-weeks of CRT (approximately 2-3 weeks on study)

• Absolute physiologic change of the primary tumor

  Following 2-weeks of CRT (approximately 2-3 weeks on study)

• Absolute volumetric change of involved nodes

  Following 2-weeks of CRT (approximately 2-3 weeks on study)

Other Outcomes (2)

• Number of Circulating Tumor Cells

  Pre-treatment (baseline) and following 2-weeks of CRT (approx. 2-3 weeks on study), 3-months post-treatment (approx. 19-23 weeks on study)

• Change in Number of Circulating Tumor Cells Between Time Points

  Pre-treatment (baseline) and following 2-weeks of CRT (approx. 2-3 weeks on study), 3-months post-treatment (approx. 19-23 weeks on study)

Study Arms (1)

Oropharynx Cancer Patients

Patients with OPSCC will be treated with comprehensive head and neck RT to 70 Gy in 33 fractions with concurrent weekly cisplatin at 40 mg/m2 and at the University of Wisconsin.

Radiation: Intensity modulated radiotherapy (IMRT); Diagnostic Test: PET-MRI

Interventions

Intensity modulated radiotherapy (IMRT) RADIATION

Intensity modulated radiotherapy (IMRT) will be delivered over 6.5 weeks in 33 daily fractions. Treatments will be initiated on Monday or Tuesday. Missed treatments will be compensated for by delivering an additional BID treatment during the week given at least 6 hours apart OR treating on the Saturday of that week, OR adding to the end of treatment. Gross disease will receive 70 Gy in 2.12 Gy fractions, areas at high-risk for subclinical disease will receive 60 Gy in 1.82 Gy fractions, and areas at low-risk for harboring subclinical disease will receive 56 Gy in 1.70 Gy fractions.

Oropharynx Cancer Patients

PET-MRI DIAGNOSTIC_TEST

All imaging data will be acquired using a 3.0T PET-MRI scanner with a standard bore size of 60 cm. Patients will be placed in standard non-ferrous head and neck immobilization devices during PET-MRI to simulate their anticipated positioning during subsequent CT simulation and treatment. A head and neck PET-MRI study will be performed with scan sequences tailored for the site of interest. The PET-MRI exam will take approximately 90 minutes to complete.

Oropharynx Cancer Patients

Eligibility Criteria

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

Study Population

Participants with OPSCC will be enrolled on an institutional review board approved clinical trial and treated with comprehensive head and neck RT to 70 Gy in 33 fractions, some with concurrent weekly cisplatin at 40 mg/m2 and at the University of Wisconsin.

You may qualify if:

• Histologically- or cytologically-proven diagnosis of squamous cell carcinoma (including papillary squamous cell carcinoma and basaloid squamous cell carcinoma variants) of the oropharynx (tonsil or base of tongue)
• III-IVB (T3N0, T1-3N1, T4aN0-3, T4bN0-3, T1-4N2, T1-4N3) (AJCC 8th edition) based upon the following minimum diagnostic workup:
• General history and physical examination (including nasolarygopharyngoscopy or indirect mirror exam) by a radiation oncologist or medical oncologist or ENT head and neck surgeon within 8 weeks prior to registration.
• Diagnostic CT of the neck with IV contrast
• Chest imaging
• CXR or CT chest without contrast
• Patient must not have any contraindications to undergoing a 3.0T PET-MRI
• Zubrod Performance Status 0-1 within 2 weeks prior to registration.
• Smoking history defined by pack-years (calculated by multiplying the number of packs of cigarettes smoked per day by the number of years the person has smoked).
• Negative urine pregnancy test within 2 weeks prior to registration for women of childbearing potential.
• Patient must provide study specific informed consent prior to study entry.

You may not qualify if:

• Cancers considered to be from an oral cavity, nasopharynx, hypopharynx, or larynx are excluded. Carcinoma of the neck of unknown primary site origin (even if p16 positive) are excluded.
• Distant metastasis
• Gross total excision of the primary tumor with or without nodal dissection.
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years. (For example, carcinoma of the breast, colon or cervix are all permissible if patients are disease free for ≥ 3 years.)
• Prior radiotherapy to the head and neck region that would result in overlap of radiation therapy fields.
• Presence of passive and/or active devices that are not compatible with the 3.0T PET/MR scanner environment. Any person with the following will be excluded: cardiac pacemaker, metal fragments in or around the eye, venous umbrella, permanent eyeliner or permanent artificial eyebrows. Patents with the following potentially non-MRI compatible devices will undergo screening using the standard UWHC MRI screening protocol by trained UWHC personnel: cardiac pacemaker, heart valve replacement, intracranial aneurysm clips, middle ear, eye, joint, or penile implants, joint replacements, implantable hearing aids, neurostimulator devices, insulin pumps, shunts/stents, metal mesh/coil implants; metal plate/pin/screws/wires, or any other metallic implants. Also, patients with anatomical constraints limiting the feasibility of MRI will be excluded.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Cancer Institute (NCI): collaborator
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Witek ME, Kimple RJ, Avey GD, Burr AR, Chandereng T, Yu M, Hu R, Wieland AM, Labby ZE, Bruce JY, Brower JV, Hartig GK, Harari PM. Prospective Study of PET/MRI Tumor Response During Chemoradiotherapy for Patients With Low-risk and Intermediate-risk p16-positive Oropharynx Cancer. Am J Clin Oncol. 2022 May 1;45(5):202-207. doi: 10.1097/COC.0000000000000910. Epub 2022 Apr 12.

  PMID: 35446279 RESULT

Related Links

• UW Carbone Cancer Center Homepage

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Oropharyngeal Neoplasms

Interventions

Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Randy Kimple, MD, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2017
• First Posted: November 17, 2017
• Study Start: May 3, 2018
• Primary Completion: February 19, 2021
• Study Completion: May 15, 2021
• Last Updated: November 21, 2022

Record last verified: 2022-11

Locations

US (1)