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The aim of this trial is to examine the feasibility, acceptability, and potential efficacy of a 12-month course of pravastatin as an antifibrotic agent for managing dysphagia (swallowing problems) in patients previously treated with radiotherapy for head and neck cancer (HNC). The purpose is to assess whether pravastatin, a medication approved in Australia for cholesterol management, can improve swallowing in people with long-term radiation-associated dysphagia following HNC treatment.
The trial will recruit 48 patients, with an anticipated accrual period of approximately 6 months. Eligible patients will be identified from the Principal Investigator's current study, ERADICATE, or through referral by a radiation oncologist or speech pathologist diagnosing radiation-induced dysphagia.
Participants will receive 40 mg of pravastatin daily for up to 12 months, with swallowing assessments conducted before, during, and after treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single arm study | Experimental | Single arm study |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pravastatin 40 Mg Oral Tablet | Drug | This trial will incorporate Pravastatin 40 mg as an off-label use for the treatment of radiation-associated dysphagia. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Feasibility of a 12 month trial investigating the use of pravastatin to treat radiation-associated dysphagia | Percentage of eligible patients who consent to recruitment and percentage of recruited (registered) patients who remain on pravastatin for 12 months and complete the 6-month follow-up assessment | From the start of pravastatin therapy to 6 months of follow up after the completion of 12 months of pravastatin therapy (total estimated time duration 18 months) |
| Preliminary evidence of efficacy of the pravastatin to treat radiation-associated dysphagia | A Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) grade decrease of at least 1-point after 12 months of pravastatin from registration. The DIGEST scale ranges between 0 to 4, with 4 being the worst outcome. | From enrolment to the end of 12 months of pravastatin use |
| Measure | Description | Time Frame |
|---|---|---|
| Acceptability of trial methods and procedures and acceptability of pravastatin | Acceptability of trial methods and procedures, and acceptability of pravastatin: Theoretical Framework of Acceptability (TFA) questionnaire total score. The TFA used in this study ranges between 11 - 55 and higher scores represent better acceptability. | From the start of pravastatin therapy to 6 months of follow up after the completion of 12 months of pravastatin therapy (total estimated time duration 18 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Clinician-rated penetration/aspiration | Clinician-rated penetration/aspiration: Penetration-Aspiration scale (PAS) score assessed via videofluoroscopy swallow studies (VFSS), the range is 1 to 8, with 8 representing the worst outcome. | From the start of pravastatin therapy to 6 months of follow up after the completion of 12 months of pravastatin therapy (total estimated time duration 18 months) |
Inclusion Criteria:
Patient has provided written informed consent using the TRADstat PICF
Patients aged 18 years or older at screening
Received curative intent (chemo)radiotherapy to the nasopharynx, oropharynx, hypopharynx or larynx at least 2 years prior to screening
Moderate-severe RAD using validated cut-offs (PAS score > 3 and/or DIGEST grading ≥ 2), identified on a VFSS conducted within the last 12 months
Adequate kidney function defined as estimated glomerular filtration rate (eGFR) ≥ 40 ml/min
Adequate hepatic function defined as:
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2 (Appendix 1)
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jacqui Frowen, PhD | Contact | +61 (03) 8559 5220 | Jacqui.Frowen@petermac.org |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peter MacCallum Cancer Centre | Recruiting | Melbourne | Victoria | 3000 | Australia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30776452 | Background | Bourgier C, Auperin A, Rivera S, Boisselier P, Petit B, Lang P, Lassau N, Taourel P, Tetreau R, Azria D, Bourhis J, Deutsch E, Vozenin MC. Pravastatin Reverses Established Radiation-Induced Cutaneous and Subcutaneous Fibrosis in Patients With Head and Neck Cancer: Results of the Biology-Driven Phase 2 Clinical Trial Pravacur. Int J Radiat Oncol Biol Phys. 2019 Jun 1;104(2):365-373. doi: 10.1016/j.ijrobp.2019.02.024. Epub 2019 Feb 15. |
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Date will not be shared due to ethical reasons.
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| ID | Term |
|---|---|
| D006258 | Head and Neck Neoplasms |
| D003680 | Deglutition Disorders |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
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| ID | Term |
|---|---|
| D017035 | Pravastatin |
| D013607 | Tablets |
| ID | Term |
|---|---|
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| Tolerability of pravastatin | Tolerability of pravastatin: percentage of patients who cease pravastatin (patient or clinician choice) due to pravastatin related toxicity using Common Toxicity Criteria for Adverse Events, Version 5.0 (CTCAE v5.0), and the range is 0 to 5, with 5 being the worst outcome | From the start of pravastatin therapy until the completion of 12 months of therapy |
| Safety of pravastatin use | Safety of pravastatin use: percentage of patients who experience ≥ Grade 2 toxicity (as per Common Toxicity Criteria for Adverse Events, Version 5.0 [CTCAE v5.0], and the range is 0 to 5, with 5 being the worst outcome) | From the start of pravastatin therapy until the completion of 12 months of therapy |
| Biomechanical swallowing measures | Bio-mechanical swallowing measures: using the Computational Analysis of Swallowing Mechanics (CASM) via VFSS, no specific range is available, however ; higher values represent better outcome. | From the start of pravastatin therapy to 6 months of follow up after the completion of 12 months of pravastatin therapy (total estimated time duration 18 months) |
| Clinician-rated functional status | Clinician-rated functional status: Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) subscale scores, the range is between 0 to 100, with higher values representing better outcomes. | From the start of pravastatin therapy to 6 months of follow up after the completion of 12 months of pravastatin therapy (total estimated time duration 18 months) |
| Trismus (limitations in mouth opening) | Trismus (limitations in mouth opening): Maximal-interincisal opening as measured using the TheraBite® Range-of-Motion scale, the range is between 0 to 70 mm, with higher values representing better outcomes. | From the start of pravastatin therapy to 6 months of follow up after the completion of 12 months of pravastatin therapy (total estimated time duration 18 months) |
| Immune-biomarker outcome | Immune-biomarker outcome: collection of 10 mL edta tube for the immune-biomarker analysis. Specific biomarker selection still under process. | At baseline and after 12 months of pravastatin treatment. |
| Patient-reported swallowing problem severity | Patient-reported swallowing problem severity: Eating Assessment Tool (EAT-10) total score, the range is between 0 to 40, with higher values representing worse outcomes. | From the start of pravastatin therapy to 6 months of follow up after the completion of 12 months of pravastatin therapy (total estimated time duration 18 months) |
| Patient-reported swallowing-related QoL: | Patient-reported swallowing-related QoL: M.D. Anderson Dysphagia Inventory (MDADI) global score, the range is between 20 to 100, with higher values representing better outcomes. | From the start of pravastatin therapy to 6 months of follow up after the completion of 12 months of pravastatin therapy (total estimated time duration 18 months) |
| Patient-reported lymphoedema and fibrosis symptoms and impacts | Patient-reported lymphoedema and fibrosis symptoms and impacts: Head and Neck Lymphedema and Fibrosis Symptom Inventory (HN-LEF), the range is between 0 to 165, with higher values representing worse outcomes. | From the start of pravastatin therapy to 6 months of follow up after the completion of 12 months of pravastatin therapy (total estimated time duration 18 months) |
| Nutritional outcomes | Nutritional outcomes: Weight and feeding tube use (percentage of nutritional requirements taken via gastrostomy tube versus oral intake) | From the start of pravastatin therapy to 6 months of follow up after the completion of 12 months of pravastatin therapy (total estimated time duration 18 months) |
| D004066 |
| Digestive System Diseases |
| D010608 | Pharyngeal Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |