High Dose Steroid Therapy (Prednisone or Methylprednisolone) for the Improvement of Symptoms of Late Radiation-Associated Lower Cranial Neuropathy in Oropharyngeal Cancer Survivors

Phase 1

Active, not recruiting

• Conditions: Cranial Nerve Disorder; Head and Neck Carcinoma; Oropharyngeal Carcinoma
• Interventions: Drug: Methylprednisolone; Drug: Prednisone; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

• Registration Number: NCT04151082
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

This phase I/II trial studies the side effect and best dose of steroid therapy (prednisone or methylprednisolone) in improving symptoms of late radiation-associated lower cranial neuropathy in oropharyngeal cancer survivors. Steroid therapy with prednisone or methylprednisolone may help to improve symptoms associated with late radiation-associated lower cranial neuropathy.

Detailed Description

PRIMARY OBJECTIVE:

I. To establish feasibility and maximum tolerated dose (MTD) of steroid therapy that provides symptomatic improvement in oropharyngeal cancer (OPC) survivors with late lower cranial neuropathy (LCNP).

SECONDARY OBJECTIVE:

I. To examine endpoints that may be sensitive to functional or symptomatic gains with steroid therapy for late LCNP in OPC survivors by characterizing changes in symptoms, functional status, quality of life (QOL), neurophysiology, and imaging studies after steroid therapy.

TERTIARY OBJECTIVE:

I. To establish a hypothesis-generating database of physiologic, functional, and patient-reported outcomes (PROs) among head and neck cancer (HNC) survivors with late lower cranial neuropathy treated with steroid therapy.

OUTLINE: This is a phase I, dose-escalation study of steroid therapy followed by a phase II study.

Patients receive prednisone orally (PO) (or by feeding tube) once daily (QD) on days 1-5 and then taper off over 2 weeks or methylprednisolone intravenously (IV) over 1 hour on days 1-5 in the absence of disease progression or unacceptable toxicity.

Study Timeline

• Study Start: 2019-10-16
• Study First Submitted: 2019-10-16
• Study First Submitted QC: 2019-11-01
• Study First Posted: 2019-11-05
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-22
• Last Update Posted: 2025-04-25
• Primary Completion: 2025-07-31
• Study Completion: 2025-07-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

• INCLUSION CRITERIA FOR CLINICAL TRIAL: Disease free adult survivors of oropharyngeal cancer
• INCLUSION CRITERIA FOR CLINICAL TRIAL: Treated with radiotherapy >= 2 years post treatment (disease status per surveillance imaging and clinical surveillance)
• INCLUSION CRITERIA FOR CLINICAL TRIAL: Late radiation-associated lower cranial neuropathy of XII with or without X nerve (LCNP cases will be considered therapy-related when imaging, physical examination, and/or biopsy fail to demonstrate structural or malignant source)
• INCLUSION CRITERIA FOR CLINICAL TRIAL: Willing and able to return for assessment post-steroid therapy
• INCLUSION CRITERIA FOR CLINICAL TRIAL: Able to complete symptom survey (MD Anderson Symptom Inventory - Head and Neck [MDASI-HN]) in validated languages: English, simplified Chinese, Filipino, Greek, Japanese, Korean, Russian, Spanish, Taiwanese
• INCLUSION CRITERIA FOR REGISTRY: Disease-free adult survivors of head and neck cancer
• INCLUSION CRITERIA FOR REGISTRY: >= 2 years post treatment (disease status per surveillance imaging and clinical surveillance)
• INCLUSION CRITERIA FOR REGISTRY: Late lower cranial neuropathy of XII with or without X nerve (LCNP cases will be considered therapy-related when imaging, physical examination, and/or biopsy fail to demonstrate structural or malignant source)
• INCLUSION CRITERIA FOR REGISTRY: Able to complete symptom survey (MDASI-HN) in validated languages: English, simplified Chinese, Filipino, Greek, Japanese, Korean, Russian, Spanish, Taiwanese

Exclusion Criteria

• EXCLUSION CRITERIA FOR CLINICAL TRIAL: Uncontrolled diabetes
• EXCLUSION CRITERIA FOR CLINICAL TRIAL: Uncontrolled hypertension (systolic > 160; diastolic > 90)
• EXCLUSION CRITERIA FOR CLINICAL TRIAL: Known gastrointestinal ulcer
• EXCLUSION CRITERIA FOR CLINICAL TRIAL: History of psychosis
• EXCLUSION CRITERIA FOR CLINICAL TRIAL: Pregnant women
• EXCLUSION CRITERIA FOR CLINICAL TRIAL: Untreated or treatment refractory obstructive pharyngoesophageal stricture
• EXCLUSION CRITERIA FOR CLINICAL TRIAL: Known history or diagnosis of bipolar disorder
• EXCLUSION CRITERIA FOR CLINICAL TRIAL: History of surgery near hypoglossal nerve path
• EXCLUSION CRITERIA FOR REGISTRY: Uncontrolled diabetes
• EXCLUSION CRITERIA FOR REGISTRY: Uncontrolled hypertension (systolic > 160; diastolic > 90)
• EXCLUSION CRITERIA FOR REGISTRY: Known gastrointestinal ulcer
• EXCLUSION CRITERIA FOR REGISTRY: History of psychosis
• EXCLUSION CRITERIA FOR REGISTRY: Pregnant women
• EXCLUSION CRITERIA FOR REGISTRY: Untreated or treatment refractory obstructive pharyngoesophageal stricture
• EXCLUSION CRITERIA FOR REGISTRY: Known history or diagnosis of bipolar disorder

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Supportive care (steroid therapy)	Methylprednisolone	Patients receive prednisone PO (or by feeding tube) QD on days 1-5 and then taper off over 2 weeks or methylprednisolone IV over 1 hour on days 1-5 in the absence of disease progression or unacceptable toxicity.
Supportive care (steroid therapy)	Quality-of-Life Assessment	Patients receive prednisone PO (or by feeding tube) QD on days 1-5 and then taper off over 2 weeks or methylprednisolone IV over 1 hour on days 1-5 in the absence of disease progression or unacceptable toxicity.
Supportive care (steroid therapy)	Questionnaire Administration	Patients receive prednisone PO (or by feeding tube) QD on days 1-5 and then taper off over 2 weeks or methylprednisolone IV over 1 hour on days 1-5 in the absence of disease progression or unacceptable toxicity.
Supportive care (steroid therapy)	Prednisone	Patients receive prednisone PO (or by feeding tube) QD on days 1-5 and then taper off over 2 weeks or methylprednisolone IV over 1 hour on days 1-5 in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose	Up to 3 weeks
Change in MD Anderson Symptom Inventory - Head and Neck (MDASI-HN) top 5 mean	Baseline up to 3 weeks

Secondary Outcome Measures

Name	Time	Method
Improvement in tongue innervation on electromyography (EMG) findings	Up to 3 years	1. EMG scores are based on a 4-point denervation potentials grade with '0' being 'none' and '4' being 'full interference patterns of potentials'.; 2. Nerve conduction study (NCS) scores are based on a 4-point scale ranging from 'none' (best) to 'severely prolonged' or 'severely reduced' (worst).
Improvement in dynamic imaging grade of swallowing toxicity (DIGEST) scores	Up to 3 years	1. DIGEST scores are rated on a 0-4 scale from 0 (best) to 4 (worst).
Changes in maximum isometric lingual strength (MILS) and lingual range of motion (LROM)	Baseline up to 3 years	1. MILS scores are rated on continuous scale from 0 (worst) to 100 (best).; 2. LROM scores are rated on an ordinal scale from 0 (worst) to 100 (best).
Changes in patient reported outcomes (PRO) on MD Anderson Dysphagia Inventory (MDADI), Performance Status Scale for Head and Neck (PSS-HN), or EuroQOL (EQ-5D)	Baseline up to 3 years	1. MDADI scores are rated on a continuous scale from 20 (worst) to 100 (best).; 2. Diet, eating, and speech subscales of PSS-HN are rated on an ordinal scale from 0 (worst) to 100 (best).; 3. EQ-5D is rated on a continuous scale from 0 (worst) to 100 (best).

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States