Proactively Intervening On Early Cranial Nerve Injury As A Delayed Sequela Of Oropharyngeal Cancer: A Randomized Feasibility Clinical Trial For Pro-Habilitation (proNERVE RCT)

September 18, 2026 updated by: M.D. Anderson Cancer Center

The goal of this clinical research study is to learn about possible intervention strategies to help control cranial neuropathy in patients after they receive radiation therapy for OPC. Four (4) strategies will be tested in this study: 1) high-dose corticosteroid therapy, 2) treatment with fremanezumab, 3) manual tongue exercise therapy, and 4) device-assisted tongue exercise therapy.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Primary Objective:

To examine the feasibility of high dose steroid therapy, CGRP inhibitor therapy (Ajovy) or behavioral therapies for early/subclinical XII neuropathy after oropharyngeal radiation.

Secondary Objective:

To estimate acceptability and achievable effect sizes for each intervention strategy.

Exploratory Objective:

To explore potential for functional preservation and mechanisms of action for each intervention strategy.

Study Type

Interventional

Enrollment (Estimated)

48

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • UT MD Anderson
        • Contact:
        • Principal Investigator:
          • Katherine Hutcheson, BA,MS,PHD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Adult (≥18 years of age)

  2. Disease-free cancer survivors evaluated at UT MD Anderson after treatment of squamous cell carcinoma (SCCA) of the oropharynx or HPV/p16+ SCCA of the head and neck of unknown primary

  3. EMG evidence of XII neuropathy with no/equivocal physical examination signs, referred to in the protocol as "early/subclinical" CN XII neuropathy

  4. Consent to parent cohort PA14-0947 for integrated longitudinal outcomes tracking in the OPC-SURVIVOR research program

  5. The effects of Ajovy®- Fremanezumab on the developing human fetus are unknown. For this reason and because CGRP agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to treatment initiation and for the duration of study treatment and for 5 months after the last dose (covering ~5 half lives). (Refer to Pregnancy Assessment Policy UT MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:

    • Postmenopausal (no menses in greater than or equal to 12 consecutive months).
    • History of hysterectomy or bilateral salpingo-oophorectomy.
    • Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
    • History of bilateral tubal ligation or another surgical sterilization procedure.

    Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

  6. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to treatment initiation and for the duration of study treatment and for 5 months after the last dose (covering ~5 half lives).

  7. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Primary surgery for OPC
  2. Documented XII nerve injury by tumor or other non-cancer treatment source
  3. History of multiple head and neck cancers or central nervous system cancer
  4. Uncontrolled diabetes
  5. Uncontrolled hypertension (systolic >160; diastolic >90)
  6. Known gastrointestinal ulcer
  7. History of psychiatric illness/social situations that would limit compliance with study requirements;
  8. Untreated or treatment refectory obstructive pharyngoesophageal stricture
  9. Known history or diagnosis of bipolar disorder
  10. Functionally limiting cardiac, pulmonary, or neuromuscular disease
  11. Recent acute coronary syndrome or stroke (within 3 months) or uncontrolled severe coronary artery disease with symptoms or coronary revascularization procedure (bypass surgery or stent within the last 3 months)
  12. Hospitalization for heart failure or known NYHA Class III-IV heart failure within the previous 6 months.
  13. Known ventricular arrhythmia requiring recent intervention (cardioversion, ablation, or antiarrhythmic initiation within 3 months), or currently symptomatic atrial fibrillation not rate-controlled.
  14. Current or planned tracheostomy or total laryngectomy
  15. Platelet <50,000/mcL
  16. Known hypersensitivity to fremanezumab-vfrm or any excipients (L-histidine, Lhistidine hydrochloride monohydrate, sucrose, disodium EDTA, polysorbate 80, water for injection)37
  17. History of serious hypersensitivity reaction to another CGRP monoclonal antibody (erenumab, galcanezumab, eptinezumab)46
  18. Pregnant and breastfeeding women are excluded from this study because the safety of Ajovy during pregnancy has not been established. Human data are insufficient to assess fetal risk, and as a monoclonal antibody, Ajovy may cross the placenta. It is also unknown whether Ajovy is present in human milk or what effects it may have on a breastfed infant. These potential risks may also apply to other agents used in this study. Pregnancy or women actively planning pregnancy during the treatment period37 and those Breastfeeding during the treatment period46
  19. Currently taking the following medications: Other CGRP antagonists (biologic or small molecule): erenumab (Aimovig®), galcanezumab (Emgality®), eptinezumab (Vyepti®), rimegepant (Nurtec®), ubrogepant (Ubrelvy®), atogepant (Qulipta®)
  20. Current cognitive or other limitations that preclude independent completion of study regimen
  21. Patients who are receiving any other investigational agents.
  22. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Ajovy®- Fremanezumab or other agents used in study.
  23. Current corticosteroid therapy prior to enrollment
  24. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High Dose Corticosteroid Therapy (Prednisone)

A high dose corticosteroid therapy 3mg/kg prednisone (±10%) per oral x 5 days with a 2-week taper (± 4 days)
Drug: Prednisone

Given orally

Other Names:
  • Deltasone
  • Rayos
  • Sterapred
Experimental: CGRP inhibitor Therapy (Ajovy-Fremanezumab)

675 mg Ajovy®- Fremanezumab (quarterly injection) targeting inhibition of CGRP-mediated sensory nerve signaling as a strategy to preserve cranial nerve function in the early injury phase.
Drug: Ajovy

Given by injection

Other Names:
  • Fremanezumab
Experimental: Manual Therapy Facilitated Lingual Exercise

Manual therapy completed 3 days weekly by the patient at home with 3 clinician directed training visits over 8 weeks.
Other: Manual Therapy

Participants will complete manual therapy 3 days a week at home with 3 clinician-directed visits over 8 weeks.
Experimental: Device-Facilitated Lingual Exercise

Device-facilitated lingual home exercise program for tongue strength and endurance completed at home by patient with 3 days weekly with 3 clinician directed training visits over 8 weeks.
Device: IOPI device

Participants will complete resistance exercise 3 days a week at home over 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Adverse Events (AEs)
Time Frame: Through study completion; an average of 1 year

Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 6.0
Through study completion; an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Investigators

  • Principal Investigator: Katherine Hutcheson, BA,MS,PHD, UT MD Anderson

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 1, 2027

Primary Completion (Estimated)

September 30, 2030

Study Completion (Estimated)

September 30, 2032

Study Registration Dates

First Submitted

September 18, 2026

First Submitted That Met QC Criteria

September 18, 2026

First Posted (Actual)

September 21, 2026

Study Record Updates

Last Update Posted (Actual)

September 21, 2026

Last Update Submitted That Met QC Criteria

September 18, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-0063
  • NCI-2026-06933 (Other Identifier: NCI-Clinical Trials Registry)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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