Long-term Adverse Effects of Radiotherapy for Pelvic CancerPhase 2PPALMNCT02230800
PPALM-Palm Oil and Pentoxifylline Against Late Morbidity
A Phase 2 study testing Tocovid SupraBio plus pentoxifylline in people with Long-term Adverse Effects of Radiotherapy for Pelvic Cancer, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Side effects are common after treatment with radiotherapy for tumours in the pelvis and can affect the way the bowel and urinary system work as well as causing sexual difficulties, skin damage and bone problems. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Long-term Adverse Effects of Radiotherapy for Pelvic Cancer
- What is being tested?
- Tocovid SupraBio plus pentoxifylline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 25 Nov 2014to 20 Dec 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age over 18 years.
- Past history of a malignant pelvic neoplasm (T1-4 N0-2 M0) of the rectum, prostate, testis, bladder, uterine cervix, uterus, vagina, vulva, anal canal or ovary.
- A minimum 12 months follow-up post-radiotherapy (24 months for patients with past history of stage T4 and/or N2 disease).
- A maximum 7 years post-radiotherapy
- No evidence of cancer recurrence.
- Gastrointestinal symptoms attributable to prior radiotherapy: grade 2 or higher in any CTCAE Version 4 category, or grade 1 with difficult intermittent symptoms.
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- Symptoms are not relieved by appropriate life-style advice and medication over a 3-month period.
- Physical and psychological fitness for Tocovid SupraBio+PTX therapy.
- Written informed consent and availability for follow up.
- Willingness to keep to a specified level of dietary fat intake during the study.
Who cannot join
- Surgery for rectal cancer.
- Contra-indication or other inability to undergo magnetic resonance imaging, if required to rule out malignancy.
- Dietary supplementation containing alpha-tocopherol above a daily dose of 30mg at any time during the last three months.
- Medication with pentoxifylline at any time since radiotherapy.
- Pregnancy or breast feeding.
- Ischaemic heart disease, uncontrolled hypertension, hypotension, acute myocardial infarction, cerebral haemorrhage, retinal haemorrhage, renal failure, liver failure and medication with insulin, ketorolac or vitamin K.
- Allergy to soya.
- Known hypersensitivity to the active constituent, pentoxifylline other methyl xanthines or any of the excipients', as per SmPC for pentoxifylline.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
About this study
Official title: Randomised Double-blind Placebo Controlled Phase II Trial of Tocovid SupraBio in Combination With Pentoxifylline (PTX) in Patients Suffering Long-term Adverse Effects of Radiotherapy for Pelvic Cancer
Side effects are common after treatment with radiotherapy for tumours in the pelvis and can affect the way the bowel and urinary system work as well as causing sexual difficulties, skin damage and bone problems. Problems in the bowel, bladder, sexual organs and skin mostly result from thickening of the tissues in response to radiotherapy, a process called "fibrosis". Fibrosis often worsens over time.
There has been progress in treating bowel symptoms which usually are the worst problem after radiotherapy. However, even after receiving the best possible treatments, while many patients are better, they are often not cured of all their difficult problems.
Read more
For some years, it has been hypothesised that if fibrosis could be treated then symptoms would improve. Recent research in laboratory animals has suggested that an effective treatment for radiation-induced fibrosis is combination therapy with a drug called Pentoxifylline together with a nutritional supplement containing gamma-tocotrienol (Tocovid SupraBio), a substance derived from palm oil. Both of these agents are simple to take and side effects are rare.
This study will recruit volunteers who continue to have difficult side effects after previous radiotherapy to the pelvis despite receiving the best treatments available from a unique clinic at The Royal Marsden which has pioneered treatment for bowel problems after radiotherapy. Two out of every three volunteers who take part, will be randomly assigned to treatment with Pentoxifylline and Tocovid SupraBio, while one out of three will receive dummy pills. Neither the patients nor the staff assessing them will know which treatment they have been given. Volunteers take the active treatments or dummy tablets for a year and will be assessed regularly while on treatment and for a year afterwards. This study will show whether active treatment is more effective than dummy pills in improving the symptoms caused by radiation-induced fibrosis.
- Being tested
- Tocovid SupraBio plus pentoxifylline, Matching placebos
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tocovid SupraBio plus pentoxifyllineDrug
Matching placebosDrug
| Study group | Role | What they receive |
|---|---|---|
| Tocovid SupraBio plus pentoxifylline (PTX) | Experimental | Tocovid SupraBio* 200mg po bd plus pentoxifylline (PTX) 400mg po bd for 12 months. Receives: Drug: Tocovid SupraBio plus pentoxifylline |
| Matching placebos | Placebo comparator | Matching placebos bd for 12 months. Receives: Drug: Matching placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change at 12 months in the bowel disease subset of the Modified IBDQ Quality of Life questionnaire.
Measured: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
Secondary outcomes (7)
Change at 12 months in rectal IBDQ bleeding score between the two groups in those patients presenting with grade 2, 3 or 4 bleeding.
Measured: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
Change at 12 months in IBDQ faecal incontinence score between the two groups in those patients presenting with grade 1 or greater incontinence.
Measured: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
Proportion of items graded as marked or severe (grade 3 or 4).
Measured: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
Physician assessment of rectal dysfunction based on the modified CTCAE Version 4 grading.
Measured: Endpoint will be assessed pre-treatment and 6, 12 & 24 months post-treatment.
Patient self-assessments: QLQ-C30 and CR29 and the Gastrointestinal Symptom Rating Scale.
Measured: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
Photographic assessment of rectal mucosa.
Measured: Endpoint will be assessed pre-treatment and 12 & 24 months post-treatment
Serum fibrosis marker levels.
Measured: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2014 (estimated)
- Study start25 Nov 2014
- Primary completion20 Dec 2019
- Study completion20 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Long-term Adverse Effects of Radiotherapy for Pelvic CancerStudies of the same condition, open and under way.
- More trials run by Royal Marsden NHS Foundation TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Malaysia Palm Oil Board
- Responsible party
- Sponsor
- Investigators
- Alexandra Taylor, Principal investigator, Royal Marsden NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02230800
- Sponsor's protocol ID
- CCR3894
- Acronym
- PPALM
- Status last verified
- Jan 2019
- First submitted
- 29 Aug 2014
- Last updated
- 23 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Andreyev HJN, Matthews J, Adams C, Gothard L, Lucy C, Tovey H, Boyle S, Anbalagan S, Musallam A, Yarnold J, Abraham D, Bliss J, Abdi BA, Taylor A, Hauer-Jensen M. Randomised single centre double-blind placebo controlled phase II trial of Tocovid SupraBio in combination with pentoxifylline in patients suffering long-term gastrointestinal adverse effects of radiotherapy for pelvic cancer: The PPALM study. Radiother Oncol. 2022 Mar;168:130-137. doi: 10.1016/j.radonc.2022.01.024. Epub 2022 Jan 29.
PubMed 35093409
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Double-blind Placebo Controlled Phase II Trial of Tocovid SupraBio in Combination With Pentoxifylline (PTX) in Patients Suffering Long-term Adverse Effects of Radiotherapy for Pelvic Cancer
- ClinicalTrials.gov ID
- NCT02230800
- Acronym / sponsor ID
- PPALM / CCR3894
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Collaborators
- Malaysia Palm Oil Board
- Study start
- 25 Nov 2014 (actual)
- Primary completion
- 20 Dec 2019 (actual)
- Study completion
- 20 Dec 2019 (actual)
- First posted
- 3 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Side effects are common after treatment with radiotherapy for tumours in the pelvis and can affect the way the bowel and urinary system work as well as causing sexual difficulties, skin damage and bone problems. Problems in the bowel, bladder, sexual organs and skin mostly result from thickening of the tissues in response to radiotherapy, a process called "fibrosis". Fibrosis often worsens over time.
There has been progress in treating bowel symptoms which usually are the worst problem after radiotherapy. However, even after receiving the best possible treatments, while many patients are better, they are often not cured of all their difficult problems.
For some years, it has been hypothesised that if fibrosis could be treated then symptoms would improve. Recent research in laboratory animals has suggested that an effective treatment for radiation-induced fibrosis is combination therapy with a drug called Pentoxifylline together with a nutritional supplement containing gamma-tocotrienol (Tocovid SupraBio), a substance derived from palm oil. Both of these agents are simple to take and side effects are rare.
This study will recruit volunteers who continue to have difficult side effects after previous radiotherapy to the pelvis despite receiving the best treatments available from a unique clinic at The Royal Marsden which has pioneered treatment for bowel problems after radiotherapy. Two out of every three volunteers who take part, will be randomly assigned to treatment with Pentoxifylline and Tocovid SupraBio, while one out of three will receive dummy pills. Neither the patients nor the staff assessing them will know which treatment they have been given. Volunteers take the active treatments or dummy tablets for a year and will be assessed regularly while on treatment and for a year afterwards. This study will show whether active treatment is more effective than dummy pills in improving the symptoms caused by radiation-induced fibrosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tocovid SupraBio plus pentoxifylline (PTX) | Experimental | Drug: Tocovid SupraBio plus pentoxifyllineTocovid SupraBio* 200mg po bd plus pentoxifylline (PTX) 400mg po bd for 12 months. |
| Matching placebos | Placebo comparator | Drug: Matching placebosMatching placebos bd for 12 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age over 18 years.
- Past history of a malignant pelvic neoplasm (T1-4 N0-2 M0) of the rectum, prostate, testis, bladder, uterine cervix, uterus, vagina, vulva, anal canal or ovary.
- A minimum 12 months follow-up post-radiotherapy (24 months for patients with past history of stage T4 and/or N2 disease).
- A maximum 7 years post-radiotherapy
- No evidence of cancer recurrence.
Key exclusion criteria (8 listed)
- Surgery for rectal cancer.
- Contra-indication or other inability to undergo magnetic resonance imaging, if required to rule out malignancy.
- Dietary supplementation containing alpha-tocopherol above a daily dose of 30mg at any time during the last three months.
- Medication with pentoxifylline at any time since radiotherapy.
- Pregnancy or breast feeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tocovid SupraBio plus pentoxifylline | Drug | Tocovid SupraBio plus pentoxifylline (PTX) |
| Matching placebos | Drug | Matching placebos |
Primary outcome
Change at 12 months in the bowel disease subset of the Modified IBDQ Quality of Life questionnaire.
Time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
7 secondary outcomes
Change at 12 months in rectal IBDQ bleeding score between the two groups in those patients presenting with grade 2, 3 or 4 bleeding.
Time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
Change at 12 months in IBDQ faecal incontinence score between the two groups in those patients presenting with grade 1 or greater incontinence.
Time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
Proportion of items graded as marked or severe (grade 3 or 4).
Time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
Physician assessment of rectal dysfunction based on the modified CTCAE Version 4 grading.
Time frame: Endpoint will be assessed pre-treatment and 6, 12 & 24 months post-treatment.
Patient self-assessments: QLQ-C30 and CR29 and the Gastrointestinal Symptom Rating Scale.
Time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
Photographic assessment of rectal mucosa.
Time frame: Endpoint will be assessed pre-treatment and 12 & 24 months post-treatment
Serum fibrosis marker levels.
Time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2019.
- Derived from this study: PubMed 35093409Andreyev HJN, Matthews J, Adams C, Gothard L, Lucy C, Tovey H, Boyle S, Anbalagan S, Musallam A, Yarnold J, Abraham D, Bliss J, Abdi BA, Taylor A, Hauer-Jensen M. Randomised single centre double-blind placebo controlled phase II trial of Tocovid SupraBio in combination with pentoxifylline in patients suffering long-term gastrointestinal adverse effects of radiotherapy for pelvic cancer: The PPALM study. Radiother Oncol. 2022 Mar;168:130-137. doi: 10.1016/j.radonc.2022.01.024. Epub 2022 Jan 29.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexandra Taylor principal investigator
Royal Marsden NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tocovid SupraBio plus pentoxifylline in people with Long-term Adverse Effects of Radiotherapy for Pelvic Cancer, run by Royal Marsden NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change at 12 months in the bowel disease subset of the Modified IBDQ Quality of Life questionnaire. (time frame: Endpoint will be assessed pre-treatment and 3, 6, 9, 12, 18 & 24 months post-treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02230800, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2019.