Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

MR LINAC

ALISON TREE

Contact Person

Currently radiotherapy for prostate cancer is directed using scans or X-Rays, which ensures the radiotherapy treatment 'hits the target' and avoids the healthy tissues around the prostate. There are two current methods of radiotherapy image guidance- either placing small gold seeds into the prostate and taking XRays or doing a small CT scan of the prostate region each day. Neither of these methods are perfect and have drawbacks and inaccuracies.

The best way to see the prostate is with an MRI scan - this shows the edge of the prostate much more clearly and can even show the area of most aggressive cancer within the prostate. Shortly the investigators will have the ability to use a new machine - an MR-Linac - which combines an MR scanner and a radiotherapy machine.

As well as giving the investigators a clearer picture, and enabling the investigators to keep watching the prostate while the participant has their treatment (not currently possible with standard machines) this new machine will also allow the investigators to change the radiotherapy plan if they can see that the internal anatomy has shifted day to day. Currently the investigators have to give the same radiotherapy plan each day, which means the investigators have to treat a 'safety margin' around to prostate to allow for these day to day anatomy changes (e.g. rectal filling).

The aim of this study is to assess the technical feasibility of delivering radical radiotherapy for prostate cancer using the MR-Linac, including the feasibility of changing the radiotherapy plan on a daily basis to mirror internal anatomy changes. The investigators will recruit 30 patients with localised prostate cancer who need radiotherapy. The team will deliver the same dose in the same number of days i.e. the same as standard radiotherapy. Side effects will also be assessed by physicians and using patient questionnaires.

To assess delivery of prostate IMRT on the MR linac

INVOLVES PROSTATE CANCER PATIENTS SO MUST BE MALE

Prostate Radiotherapy Integrated With Simultaneous MRI (The PRISM Study)

ANONYMISED DATA WILL BE SHARED WITHIN THE ELEKTA CONSORTIUM

The radiotherapy timing sheet will be used to record the length of time for patients to have their MR guided adaptive radiotherapy for each fraction. This information will then inform if treatment can be given in a clinically feasible time frame.

Royal Marsden NHS Foundation Trust

MR-guided radiotherapy using the Alberta linac-MR P3 system. Contemporary radiotherapy techniques and fractionation schedules will be conducted in the following graduated stages with overlap between stages allowed:

Stage 1: Parallel-opposed pair treatments (palliative) Stage 2: 4 field box and breast treatments (curative or palliative) Stage 3: Radical treatments - multi-field 3DCRT (curative) Stage 4: Radical treatments - multi-field IMRT (curative)

MR guided radiotherapy using the Alberta linac-MR P3 system

MR guided radiotherapy

Nawaid Usmani, MD

Cancers are often treated with external beam radiotherapy. Current radiotherapy treatments are performed using computed tomography (also known as CT) scans which may not always clearly identify the cancer. In some instances, magnetic resonance imaging (MRI) may be able to better identify cancers. Therefore, efforts are currently underway to use the MRI scans to improve radiotherapy treatments or eventually even use radiotherapy equipment that only uses MRI scans to guide treatments. This new technology that will only use MRI scans to guide treatments is called the Linac-MR (linear accelerator with an MRI). This new Linac-MR is a unique innovation at the Cross Cancer Institute, with theoretical advantages over other Linac-MR machines that are being tested elsewhere in the world. This feasibility study is being done as a first step in clinical development of the Linac-MR, as this new technology has to be tested to see if it is acceptable to both doctors and participants. The purpose of this Phase I/II study is (1) to verify treatment completion as intended and scheduled the oncology team, and (2) to evaluate treatment effects, including any expected or unexpected radiation side effects and cancer response to radiation. This study will allow the researchers at the Cross Cancer Institute to develop this technology further by conducting additional studies to take advantage of MRI scanning on tumor tracking during radiation treatments.

This prospective, open-label, Phase I/II, clinical trial is feasibility study to evaluate MR-guided radiotherapy with the Alberta linac-MR P3 system in adult patients with cancer that are treated with external beam radiotherapy in four graduated stages (described below), progressing from palliative participants with simple techniques to curative participants with complex techniques, with progression to each stage determined by an internal SAFE review committee. Conventional treatment margins and doses will be utilized, with the MR being utilized in place of CT based imaging. The intent is to replicate current CT based treatments on the Alberta linac-MR P3 system using MR guided imaging, planning and treatment delivery. MR imaging will be utilized for simulation, planning and image guidance. Dosimetry will be done as per standard of care. MRI contrast may be used, as applicable. Adverse events will be collected weekly during RT, and participants will complete one questionnaire at the end of their RT treatment. Follow-up will consist of adverse event assessment at 1, 3, 6, and 12 months following completion of RT, and may be assessed annually via chart review for up to 5 years. Survival status will be assessed at 12 months following completion of RT, and then annually for up to 5 years.

In stage 1, 10 to 28 participants with incurable malignancies that require palliative radiotherapy with parallel-opposed pair beam arrangements will be enrolled. These will be patients with bone or brain metastases from their malignancies that require either a single fraction or multiple fractions of radiotherapy. The treatment will be a simple opposed pair beam arrangement to a dose of a single 8 Gy or to a dose of 20 Gy over a course of 5 fractions. Once some initial treatments are completed, and at the discretion of an internal SAFE review committee, additional treatment sites will be permitted (i.e. lung, abdomen, etc.) that are also utilizing a simple opposed pair beam arrangement with the above doses.

In stage 2, 10 to 28 participants with malignancies (curative or palliative treatments) that require multi-field arrangement for their external beam radiotherapy will be enrolled. Initially, 4 field techniques (anterior, posterior, right lateral, left lateral) will be utilized to treat central tumors using fractionation schemes that are currently considered standard of care. Patients with pelvic malignancies (i.e. rectal cancers, cervical cancers, endometrial cancers) or other malignancies requiring simple four field techniques will be identified for this stage. As well, breast patients requiring a simple tangential opposed pair beam arrangement or 3 - 4 field technique (to include the supraclavicular nodal regions) will be enrolled, with preference for standard hypofractionation schedules, if possible.

In stage 3, 10 to 28 participants with malignancies (primarily curable, but incurable malignancies may also be considered) that require more complicated multi-field 3DCRT treatments (not requiring IMRT) for their external beam radiotherapy (i.e. lung, brain, etc.) will be enrolled. This will include the use of field-in-field techniques such as step-and-shoot techniques to allow for modulation of the radiation beam during treatment.

In stage 4, 10 to 28 participants with malignancies (primarily curable, but incurable malignancies may also be considered) that require more complicated multi-field IMRT treatments for their external beam radiotherapy (i.e. prostate, head and neck, lung, brain, etc.) will be enrolled.

Northern Alberta Linac-MR Image-Guided Radiotherapy (Northern LIGHTs-2)

Northern Alberta Linac-MR Image-Guided Human Clinical Trials - 2

The total number of participants completing, without clinically unacceptable interruptions, a course of treatment on the Alberta linac-MR P3 system. The study will track the number of participants that complete treatment without any significant interruptions or delays in their treatment.

Acute toxicity (within 6 months post treatment) graded according to CTCAE version 5.0 will be assessed when all participants have completed a minimum of 1 year follow-up.

Late toxicity (greater than 6 months post treatment) graded according to CTCAE version 5.0 will be assessed when all participants have completed a minimum of 1 year follow-up.

Participants will complete a questionnaire at the end of their MR guided radiotherapy. The questionnaire will assess participant comfort and their perception of the treatment experience using a 1 - 5 scale.

The total MR guided radiotherapy time will be recorded for each participant, which is comprised of the sum of time the participant is in the treatment room and the total treatment time daily. The overall treatment duration should not exceed the original scheduled treatment duration via conventional radiotherapy by more than five business days, in case of unexpected servicing needs or any other delays.

The total treatment planning time using the Linac-MR will be recorded for each participant. The overall treatment planning time should be within the currently accepted ready to treat timelines for conventional radiotherapy.

Time from treatment until the recurrence of disease locally.

Time from treatment until the recurrence of disease (or death).

Time from treatment until death from any cause. Survival status will be assessed at 12 months following completion of treatment, then annually for up to 5 years.

AHS Cancer Control Alberta

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Pancreatic Cancer

Patients in the intervention arm will receive locally ablative stereotactic MRgRT in addition to standard of care, consisting of 5 times 10 Gy MR guided radiotherapy.

Patients randomized to the control arm will continue standard of care as described without additional local treatment.

5 fractions of 10 Gray MRgRT in addition to standard of care

Lois Daamen, MD, PhD

Jacobien Scheepens, MD

J. C.M. Scheepens, MD

H. M.U. Peulen, MD, PhD

A. M.E. Bruynzeel, MD, PhD

H. D. Heerkens, MD, PhD

L. A. Daamen, MD, PhD

M. P.W. Intven, MD, PhD

M P.W. Intven, MD, PhD

J. J. Bosch

A randomized controlled trial comparing the effect of local ablative MR-guided radiotherapy (MRgRT) after systemic therapy with current standard treatment alone, on health-related quality of life in patients with locally advanced pancreatic cancer (LAPC).

Rationale: About 40% of patients with pancreatic cancer are diagnosed with locally advanced pancreatic cancer (LAPC). Recommended treatment consists of chemotherapy to prevent disease dissemination and prolong survival. Nevertheless, local tumor growth often causes severe morbidity, including pain, gastrointestinal obstruction, and malnutrition. This has a substantial negative impact on health-related quality of life (HRQoL). Eventually, one-third of patients die due to local tumor growth rather than from systemic disease spread. For palliation of symptoms and improved local tumor control, potentially prolonging survival, minimally-invasive ablative therapies may be effective. Online adaptive stereotactic Magnetic Resonance-guided radiotherapy (MRgRT) is an innovative treatment modality that enables high-precision ablative radiotherapy for pancreatic tumors. This potentially improves RT efficacy without increasing the risk of RT-related toxicity. Consequently, MRgRT holds promise for the treatment of pancreatic cancer.

Objective: To investigate the efficacy of stereotactic MRgRT on HRQoL deterioration-free survival, including death as an event, in patients with LAPC after systemic chemotherapy.

Study design: Nationwide randomized controlled trial (1:1 randomization).

Study population: Patients with LAPC according to Dutch Pancreatic Cancer Group (DPCG) criteria who are not eligible for tumor resection after at least two months of chemotherapy (sample size 150 patients). Also, patients with LAPC who are eligible but choose to refrain from chemotherapy and/or surgery can participate in this trial.

Intervention: Patients in the intervention arm receive 50Gy MRgRT in five fractions over two weeks in one of the four Consortium Centers, followed by standard care, either consisting of continuation of chemotherapy or best supportive care. Patients in the control arm continue standard care without ablative MRgRT.

Main study endpoints: The primary outcome is HRQoL deterioration-free survival from the time of randomization, defined as the Time Until Definitive Deterioration (TUDD) including death as an event. HRQoL is evaluated using the EORTC QLQ-C30 Summary Score. The TUDD is defined as a 10-point minimal clinically important difference compared to baseline, with no further improvement of ≥10 points afterwards. All patients will be offered home monitoring using the Trial@home platform to decrease the burden of trial participation.

Locally Advanced Pancreatic Cancer After Systemic Therapy: Ablative MR-guided Radiotherapy

Locally Advanced Pancreatic Cancer After Systemic Therapy: Ablative MR-guided Radiotherapy, a Randomized Controlled Trial

De-dentified data generated during the LAPSTAR trial will be made available to other researchers upon request from L.A. Daamen

HRQoL deterioration-free survival is defined as the Time Until Definitive Deterioration (TUDD) including death from any cause, calculated from the time of randomization. HRQoL is primarily assessed using the EORTC QLQ-C30 (version 3.0) Summary Score.

The time interval between LAPC diagnosis and either death from any cause or last follow-up

Part of the Patient Reported Outcome Measures (PROMs) using EORTC QLQ-PAN26

Part of the Patient Reported Outcome Measures (PROMs) using EORTC QLQ-C30

Part of the Patient Reported Outcome Measures (PROMs) using EQ5D-5L

To assess continuation of systemic therapy and/or administration of subsequent treatments (e.g., surgery, second-line systemic treatment, experimental treatment in clinical studies etc.), recommendations from multidisciplinary team meetings, reasons for refraining from recommended therapy, and reasons for discontinuation of therapy (i.e., start of best supportive care)

To assess tumor response on imaging according to RECIST criteria in patients who received imaging procedures during follow-up (no part of the trial follow-up)

To assess serum CA 19-9 response in patients in whom serum CA 19-9 is measured (no part of the trial follow-up)

To assess the feasibility of the Trial@home monitoring via the Withings Steel HR smartwatch for home monitoring of pancreatic cancer patients.

Compliance Withings Steel HR smartwatch (wear-time): amount of time (hours) in a day that the participant wears the smartwatch. This is calculated by the amount of time the device registers a heart rate. Patients wearing the device for \>50% of the observation period will be considered as feasible.

To assess the feasibility of the Trial@home monitoring via the Body+ scale for home monitoring of pancreatic cancer patients.

Compliance rates Body+ scale: compliance with weekly weight measurements is calculated by the number of completed weight measurements divided by the total amount of weeks in the observation period. A compliance rate of at least 75% will be considered as feasible.

To assess the feasibility of the Trial@home monitoring via the Whitings Sleep for home monitoring of pancreatic cancer patients.

Compliance Whitings Sleep: compliance with daily sleep monitoring is calculated by the number of nights sleep is measured. A compliance rate of at least 75% nights per week will be considered as feasible.

To assess the feasibility of the Trial@home monitoring via the ePRO application for home monitoring of pancreatic cancer patients.

Compliance questionnaires through the ePROapplication: A compliance rate of at least 75% from the scheduled assessments will be considered as feasible.

To exploratively generate digital biomarkers and quantify the correlation between data obtained from the Trial@home platform (Withings Steel HR smartwatch, a Withings Body+ Scale, a Withings Sleep, ePRO) and clinical endpoints (e.g., unplanned hospitalizations, early signs of adverse events, clinical deterioration, performance status, quality of life)

To assess acute (3 months) RT-related toxicity measured from the start of MRgRT, according to CTCAE v527

To assess correlation of diffusion weighted images at each treatment fraction and the possible correlation with outcomes for patients treated on a 1.5T MR-Linac

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prostate Radiotherapy Integrated With Simultaneous MRI (The PRISM Study)	NCT03658525	Prostate Cancer	MR LINAC	-	Royal Marsden NHS Foundation Trust
Northern Alberta Linac-MR Image-Guided Radiotherapy (Northern LIGHTs-2)	NCT05413473	Cancer	MR guided radio...	18 Years -	AHS Cancer Control Alberta
Locally Advanced Pancreatic Cancer After Systemic Therapy: Ablative MR-guided Radiotherapy	NCT06272162	Locally Advance...	MR guided radio...	18 Years -	UMC Utrecht
Prostate Radiotherapy Integrated With Simultaneous MRI (The PRISM Study)	NCT03658525	Prostate Cancer	MR LINAC	-	Royal Marsden NHS Foundation Trust

Spots Global Cancer Trial Database for mr guided radiotherapy