Bone Toxicity Following Pelvic Radiotherapy

Study Overview
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Brief Summary
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A randomised controlled clinical feasibility trial to determine the feasibility and acceptability of a musculoskeletal health package (MHP) intervention in women undergoing pelvic radiotherapy for gynaecological malignancies and inform power calculations for a definitive trial.

Official Title
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Bone Toxicity Following Pelvic Radiotherapy: A Prospective Randomised Controlled Feasibility Study Evaluating a Musculoskeletal Health Package in Women With Gynaecological Cancers Undergoing Pelvic Radiotherapy

Conditions
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Gynecologic Cancer, Radiotherapy Side Effect, Fracture

Intervention / Treatment
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* Combination Product: Musculoskeletal health package


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age over 18 years histologically confirmed uterine or cervix cancer patients undergoing potentially curative/adjuvant radiotherapy ability to give informed consent to participate Exclusion Criteria: age less than 18 years or greater than 85 years patients with pre-existing bone conditions such as: osteoporosis treated with bisphosphonates in the previous 5 years/fibrous dysplasia/osteogenesis imperfecta or other metabolic bone condition inability to give informed consent to participate home address outside Greater Manchester contraindication or intolerance of Magnetic Resonance scanning

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomly assigned to either an observational arm or an interventional arm consisting of a musculoskeletal health package
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of Care<br>No intervention. Standard of care cancer pathway followed. | |
| Active Comparator: Musculoskeletal Health Package<br>3 month prehabilitation exercise program during radiotherapy and assessment of BMD at baseline with appropriate management according to fracture risk assessment (with either (a) lifestyle advice, (b) calcium and vitamin D (c) calcium, vitamin D and bisphosphonate (alendronate)) | Combination Product: Musculoskeletal health package<br>* 3 month prehabilitation exercise program during radiotherapy with assessment of BMD at baseline with appropriate management according to fracture risk assessment (with either (a) lifestyle advice, (b) calcium and vitamin D (c) calcium, vitamin D and bisphosphonate (alendronate))<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eligibility and screening rate | proportion of patients eligible for the study from the patient population | baseline | 
| Recruitment and study group allocation rate | number of eligible patients recruited, randomised and allocated to appropriate study populations | 2 weeks post consent | 
| Recruitment and study group allocation rate | proportion of eligible patients recruited, randomised and allocated to appropriate study populations | 2 weeks post consent | 
| Intervention fidelity rate | number of patients completing the elements of the study | end of study 18 months | 
| Intervention fidelity rate | proportion of patients completing the elements of the study | end of study 18 months | 
| Attrition rate | number of patients lost to follow-up | end of study 18 months | 
| Patient and physician acceptability y | Patient and physician acceptability assessed with electronic questionnaires | change from baseline to 6 months | 
| Patient and physician acceptability y | Patient and physician acceptability assessed with electronic questionnaires | change from baseline to 12 months | 
| Patient and physician acceptability y | Patient and physician acceptability assessed with electronic questionnaires | change from baseline to 18 months | 
| Health Economic QOL Analysis | EuroQol-5D-5L Quality of Life assessment | change from baseline to 6 months | 
| Health Economic QOL Analysis | EuroQol-5D-5L Quality of Life assessment | change from baseline to 12 months | 
| Health Economic QOL Analysis | EuroQol-5D-5L Quality of Life assessment | change from baseline to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Radiotherapy Related Insufficiency Fracture (RRIF) | Incidence of RRIF assessed by MR | assessed at 6, 12 , 18 months post radiotherapy | 
| Longitudinal change in BMD | BMD measured by DXA at baseline and 18 months | assessed at baseline and 18 months | 
| Longitudinal change in fracture risk using FRAX (inc BMD by DXA) | FRAX assessment tool (including femoral neck BMD) | assessed at baseline and 18 months | 
| Longitudinal change in biochemical markers of bone turnover (BTM) | serum Bone Turnover Markers | change from baseline to week 2 | 
| Longitudinal change in biochemical markers of bone turnover (BTM) | serum Bone Turnover Markers | change from baseline to week 3 | 
| Longitudinal change in biochemical markers of bone turnover (BTM) | serum Bone Turnover Markers | change from baseline to week 4 | 
| Longitudinal change in biochemical markers of bone turnover (BTM) | serum Bone Turnover Markers | change from baseline to week 5 | 
| Longitudinal change in biochemical markers of bone turnover (BTM) | serum Bone Turnover Markers | change from baseline to week 6 | 
| Longitudinal change in biochemical markers of bone turnover (BTM) | serum Bone Turnover Markers | change from baseline to week 7 | 
| Longitudinal change in biochemical markers of bone turnover (BTM) | serum Bone Turnover Markers | change from baseline to week 8 | 
| Longitudinal change in biochemical markers of bone turnover (BTM) | serum Bone Turnover Markers | change from baseline to week 9 | 
| Longitudinal change in biochemical markers of bone turnover (BTM) | serum Bone Turnover Markers | change from baseline to 6 months | 
| Longitudinal change in biochemical markers of bone turnover (BTM) | serum Bone Turnover Markers | change from baseline to 12 months | 
| Longitudinal change in biochemical markers of bone turnover (BTM) | serum Bone Turnover Markers | change from baseline to 18 months | 
| Quality of Life Assessment : adapted CTCAE pelvic questionnaire | CTCAE pelvic questionnaire, (common terminology criteria for adverse events). (measures: Bowel questions scored out of 22, urinary questions out of 19 and sexual questions out of 8. Total out of 49: higher score = worse quality of life) | change from baseline to 6 months | 
| Quality of Life Assessment : adapted CTCAE pelvic questionnaire | CTCAE pelvic questionnaire, (common terminology criteria for adverse events). (measures: Bowel questions scored out of 22, urinary questions out of 19 and sexual questions out of 8. Total out of 49: higher score = worse quality of life) | change from baseline to 12 months | 
| Quality of Life Assessment : adapted CTCAE pelvic questionnaire | CTCAE pelvic questionnaire, (common terminology criteria for adverse events). (measures: Bowel questions scored out of 22, urinary questions out of 19 and sexual questions out of 8. Total out of 49: higher score = worse quality of life) | change from baseline to 18 months | 
| Quality of Life Assessment: SMFA adapted to lower limbs | adapted SMFA : short form musculoskeletal function assessment (scores are standardised with high scores indicating poor function. 39 questions min score possible 39, max score possible 195 (raw scores) | change from baseline to 6 months | 
| Quality of Life Assessment: SMFA adapted to lower limbs | adapted SMFA : short form musculoskeletal function assessment (scores are standardised with high scores indicating poor function. 39 questions min score possible 39, max score possible 195 (raw scores) | change from baseline to 12 months | 
| Quality of Life Assessment: SMFA adapted to lower limbs | adapted SMFA : short form musculoskeletal function assessment (scores are standardised with high scores indicating poor function. 39 questions min score possible 39, max score possible 195 (raw scores) | change from baseline to 18 months |