Fibrosis, Fibrosis Syndrome, Head &Amp; Neck Cancer, Lymphedema
Conditions
Brief summary
To find out if adding medication can help treat or prevent lymphedema and/or fibrosis related to radiation therapy, in survivors of head and neck cancer. Researchers will compare these drugs to find the most effective therapy for preventing or limiting these side effects.
Detailed description
Primary Objectives 1. Determine the relative utility of candidate agents to reduce clinician-rated radiation lymphedema/fibrosis 1. Hyp 1: Participants receiving candidate agent(s) will exhibit a proportional lower rate of Common Toxicity Criteria- Adverse Event (CTC-AE v5.0) rating of Grade 2 or greater on either "Fibrosis deep connective tissue" or "Superficial soft tissue fibrosis" by formal clinician assessment at 12 months post-randomization. 2. Hyp 2: Participants receiving candidate agent(s) will exhibit a proportional lower rate of objective lymphedema/fibrosis rated as "moderate/severe" grade at any head and neck subsite as measured by the Head and Neck External Lymphedema and Fibrosis (HN-ELAF) Assessment Criteria by a certified lymphedema specialist at 12 months post-randomization. 2. Determine the relative effect size observed of candidate agent(s) to reduce objective imaging-derived measures of radiation lymphedema/fibrosis-related sequalae \[Primary\] 1. Hyp 3: Participants receiving candidate agent(s) will exhibit a proportionally lower rate of objective DIGEST-detected swallowing dysfunction 12 months post-randomization. 2. Hyp 4: Participants receiving candidate agent(s) will exhibit a proportional lower rate of objective MRI-detected difference between 6- and 18-month post-randomization quantitative T1 (T1 mapping) intensity for paired muscle swallowing/neck/masticator muscles receiving \>=40Gy post-randomization. Secondary Objectives 1. Determine the relative effect size observed of candidate agent(s) to reduce patient reported measures of toxicity associated with lymphedema/fibrosis-related sequalae \[Secondary\] 1. Hyp 5: Participants receiving candidate agent(s) will exhibit a proportionally lower rate of moderate-severe rated items "Fibrosis deep connective tissue" or "Superficial soft tissue fibrosis" by patient self-assessment using the Participant Reported Outcomes-CTCAE (PROCTCAE) Scale at 12-months post-randomization. 2. Hyp 6: Participants receiving candidate agent(s) will exhibit a proportionally lower rate of moderate-severe rated symptom items by participant self-assessment using the Head and Neck External Lymphedema and Fibrosis (HN-ELAF) Symptom Inventory Scale at 12-months post-randomization. 3. Hyp 7: Participants receiving candidate agent(s) will exhibit a proportionally lower rate of moderate-severe global symptom burden by participant self-assessment using the MD Anderson Symptom Inventory Scale at 12-months post-randomization. 4. Hyp 8: Participants receiving candidate agent(s) will exhibit a proportionally improved global quality of life as denoted by patient self-assessment using the EQ-5D Visual analogue Scale at 12-months post-randomization. .
Interventions
Given PO
DRUGPentoxifylline
Given PO
DRUGketoprofen
Given PO
DRUGPirfenidoneone
Given PO
OTHERStandard of Care (SOC)
SOC
DRUGtocopherol
Given PO
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
Eligibility Criteria Eligibility criteria (observational registry or randomization) 1. Prior history of head and neck cancer with no active disease. 2. Treated previously with radiotherapy with prescribed dose (greater or equal to 30Gy) to unilateral or bilateral neck(s) 3. Detectable CTC-AE G2+ lymphedema/fibrosis at \>6 months post-radiotherapy. 4. No active liver disease (Child-Pugh class B-C), cirrhosis, nor active alcoholism, nor history of ulcers. 5. No history of myopathy/rhabdomyolysis. 6. Creatinine clearance \<30mL/min. 7. No history of acute myocardial infarction or severe coronary disease. 8. Non-pregnant/post-menopausal, or male. 9. No history of diabetes mellitus 10. Allergy/hypersensitivity to HMG Co-A reductase inhibitor and/or xanthine derivatives, e.g., caffeine, theophylline, theobromine 11. No contraindications for magnetic resonance imaging a Subject to the discretion of the treating physician and Principal Investigator (PI), as the MRI may be optional
Exclusion criteria
1. Active liver disease (Child-Pugh class B-C), cirrhosis, nor active alcoholism. 2. History of myopathy/rhabdomyolysis. 3. History of acute myocardial infarction or severe coronary disease. 4. Pregnant/post-menopausal, or male. 5. History of diabetes mellitus. 6. Allergy/hypersensitivity to Hydroxymethylglutaryl-coenzyme A (HMG Co-A) reductase inhibitor and/or xanthine derivatives, e.g., caffeine, theophylline, theobromine. 7. Contraindications for MRI Subject to the discretion of the treating physician and Principal Investigator (PI), as the MRI may be optional 8. Participants who are receiving any other investigational agents. 9. History of allergic reactions attributed to compounds of similar chemical or biologic composition to statins, hemorheologic agents or other agents used in study 10. Participants with psychiatric illness/social situations that would limit compliance with study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and adverse events | Through study completion; an average of 1 year | Incidence of Adverse of Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events |
Countries
United States
Contacts
CONTACTClifton Fuller, MD
PRINCIPAL_INVESTIGATORClifton Fuller, MD
M.D. Anderson Cancer Center
Outcome results
None listed