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

Official title

Stop LCNP: High Dose Steroid Therapy for Late Radiation-Associated Lower Cranial Neuropathy: A Phase I/II Dose Finding Trial and Data Registry

Overview

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.

Interventions

• Drug Methylprednisolone
  Given IV
• Drug Prednisone
  Given PO
• Other Quality-of-Life Assessment
  Ancillary studies
• Other Questionnaire Administration
  Ancillary studies

Primary outcome measures

• Maximum tolerated dose [Time frame: Up to 3 weeks]
• Change in MD Anderson Symptom Inventory - Head and Neck (MDASI-HN) top 5 mean [Time frame: Baseline up to 3 weeks]

Secondary outcome measures (4)

• Improvement in tongue innervation on electromyography (EMG) findings [Time frame: Up to 3 years]
• Improvement in dynamic imaging grade of swallowing toxicity (DIGEST) scores [Time frame: Up to 3 years]
• Changes in maximum isometric lingual strength (MILS) and lingual range of motion (LROM) [Time frame: Baseline up to 3 years]
• 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) [Time frame: Baseline up to 3 years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Supportive care

Study locations

United States · 1 center

• M D Anderson Cancer Center — Houston

Identifiers

NCT: NCT04151082 · 2019-0207 · NCI-2019-06735 · 2019-0207

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗