Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Immune System Diseases

Rare Diseases

Prostatic Neoplasms

Hypersensitivity

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Kennedy Disease

All Drugs and Chemicals

Antineoplastic Agents

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Micronutrients

Vitamins

Androgens

Hormones

Niraparib

Docetaxel

Abiraterone Acetate

Prednisolone

Pluvicto

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Poly(ADP-ribose) Polymerase Inhibitors

Mineralocorticoids

Ascorbic Acid

Methyltestosterone

Testosterone

Testosterone undecanoate

Testosterone enanthate

Testosterone 17 beta-cypionate

Estrogens, Conjugated (USP)

Estrogens

Tubulin Modulators

Antimitotic Agents

Glucocorticoids

Hormone Antagonists

Antineoplastic Agents, Hormonal

Protective Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Antioxidants

Trace Elements

Anabolic Androgenic Steroids

Anabolic Agents

Radiopharmaceuticals

Vitamin C

SoC (ADT + ARSI ± docetaxel + local RT) + SABR

SoC (ADT + ARSI ± docetaxel ± local RT)

SoC (ADT + ARSI ± docetaxel ± local RT) + 177Lu-PSMA-617

SoC (ADT + Apalutamide ± docetaxel ± local RT)

SoC (ADT ± docetaxel ± local RT) + Nira-AA+P

SABR is a way of giving focused high-dose radiotherapy. SABR given with a dose fractionation schedule of 30Gy in 3-5 fractions over 1-2 weeks to up to 5 metastatic lesions in the bone and/or non-regional (extra-pelvic) lymph nodes.

Stereotactic Ablative Body Radiotherapy (SABR)

177Lu-PSMA-617 is a nuclear medicine therapy. Patients will receive 177Lu-PSMA-617 to a dose of 7.4GBq. Each cycle will consist of 2 doses, 1 week apart (on day 1 and day 8) and will last 6 weeks. Treatment will be given for up to 3 cycles (6 doses).

177Lu-PSMA-617

Combination product containing Niraparib (PARP inhibitor) and Abiraterone Acetate (ARSI). The regular-strength dual-action tablet (DAT) contains 100 mg niraparib/500mg AA per tablet. Patients take 2 tablets a day and receive a of total dose 200 mg niraparib/1000 mg AA. A low-strength DAT tablet containing 50 mg niraparib/500 mg AA may be available for participants requiring a dose reduction of niraparib.

Niraparib and Abiraterone Acetate Dual Action Tablet DAT

Abiraterone Acetate is an ARSI. Single agent Abiraterone Acetate may be used in patients randomised to receive Niraparib and Abiraterone Acetate.

Apalutamide is an ARSI administered as a 240mg oral dose (four tablets taken together at the same time every day) with or without food. It is given daily in 28-day cycles.

Apalutamide

Long-term, continuous treatment with ADT (bilateral orchidectomy, LHRH agonists or LHRH antagonists) if not previously surgically castrated. The choice of ADT is at the discretion of the investigator. This will be given as standard of care as per local guidelines.

Androgen Deprivation Therapy (ADT)

Second generation ARSI (Abiraterone Acetate and Prednisolone \[AA+P\], Enzalutamide, Apalutamide or Darolutamide). This will be given as standard of care as per local guidelines.

Abiraterone acetate will be administered as a single 1000mg once daily dose (4 tablets to be taken together once a day) with prednisolone 5mg once daily to prevent secondary mineralocorticoid excess.

Enzalutamide will be administered as a 160mg oral dose (four capsules taken together at the same time every day) with or without food. Enzalutamide is administered daily in 28-day cycles.

Apalutamide will be administered as 240mg oral dose (four tablets taken together at the same time every day) with or without food. Apalutamide is administered daily in 28-day cycles. Patients require thyroid function monitoring.

Darolutamide will be administered as 600mg oral dose (two 300mg tablets taken together) with or without food. Darolutamide is administered twice daily in 28-day cycles.

Androgen Receptor Signalling Inhibitor (ARSI)

Either 36.25Gy given in 5 fractions over 1-2 weeks to prostate or 60Gy in 20 fractions over 4 weeks to prostate (± 47Gy in 20 fractions to pelvic lymph nodes ± 51Gy in 20 fractions boost to involved nodes).

Local Radiotherapy

Prednisolone should also be administered 5mg daily using local pharmacy prescribing.

Maximum of 6 cycles every 3 weeks may be given at a dose of 75mg/m2 by IV infusion.

Pamela Niem

Lorna O'Shea

Louise Brown

Nick James

STAMPEDE2 is a clinical trial comparing three new treatments with standard of care in people with prostate cancer that has spread to other parts of the body and is responsive to hormone therapy. People from all backgrounds and ethnicities are encouraged to take part and multiple hospitals across the UK are involved. University College London is running the trial.

Each comparison within the trial has its own control arm where people get the best standard of care (Arm A) versus a research arm where a new treatment is added to standard of care.

Participants are allocated to an arm by a computerised system with a 50% chance of getting the research treatment.

Comparison S: Arm A versus Arm S (Stereotactic Ablative Body Radiotherapy (SABR)) - Tests whether giving targeted doses of radiotherapy (SABR) to parts of the body where the cancer has spread slows the spread of the cancer and improves survival. 2476 people will be in this comparison.

Comparison P: Arm A versus Arm P (PSMA-Lutetium (177Lu-PSMA-617)) - Tests whether giving a radioactive material (177Lu-PSMA-617) that targets prostate cancer cells slows the spread of the cancer and improves survival. 1756 people will be in this comparison.

Comparison N: Arm A(N) versus Arm N (Niraparib-Abiraterone Acetate+Prednisolone (Nira-AA+P)) - Tests whether giving a new drug (Nira-AA+P) slows the spread of the cancer and improves survival. Only people with certain genetic changes in their tumour sample can take part in Comparison N. 682 people will be in this comparison.

Participants may be able to take part in more than one comparison.

All participants will be followed up with scans and tests to monitor their cancer. Doctors will check for any side effects from the treatments. Treatments will be stopped if side effects are serious, or people no longer wish to take the treatments.

Platform trial testing three research comparisons where patients are randomised either to experimental treatments in Arms S, P and N or their corresponding SoC control Arms A and A(N).

A Randomised Controlled Platform Trial Testing Treatments in Metastatic Hormone Sensitive Prostate Cancer

Studying Treatments in Patients Receiving Androgen Deprivation Therapy (ADT) and Androgen Receptor Signalling Inhibitors (ARSI) for Metastatic Prostate Cancer: Evaluation of Drug and Radiation Efficacy: A 2nd Multi-arm Multi-stage Randomised Controlled Trial (STAMPEDE2).

Data will be shared according to the CTU's controlled access approach based on principles outlined in the trial protocol.

Requests for sharing data will need to provide detail on the specific requirements, proposed research, qualifications of researchers and publication plan. All non-identifiable data will be available for sharing if approved following the CTU review process. Access to the digital image repository and the stored pathological tissue from researchers outside of the MRC CTU will be obtained through a formal data sharing application detailing the specific requirements, proposed research, investigator qualifications and publication plan. Applications for access to tissue are required separately from access to the shared clinical data.

rPFS is defined as the time from randomisation to progression of metastatic prostate cancer confirmed by radiographic imaging or death from any cause. The definition for rPFS requires at least one of the following four criteria to be met:

1. Radiological metastatic progression by RECIST v1.1,
2. Progression of bone metastases as defined by PCWG3,
3. Symptomatic skeletal-related events secondary to cancer progression,
4. Death from any cause.

Note: Dual-primary outcomes of radiographic Progression-Free-Survival (rPFS) and Overall Survival (OS).

The final reporting times of rPFS for each comparison below will depend on the recruitment rates and the accuracy of assumed median survival times in the sample size calculations.

OS is defined as time from randomisation to death from any cause.

Note: Dual-primary outcomes of radiographic Progression-Free-Survival (rPFS) and Overall Survival (OS).

The final reporting times of OS for each comparison below will depend on the recruitment rates and the accuracy of assumed median survival times in the sample size calculations. Please note that a closed test approach has been used for OS as a dual primary outcome. Continuation of FU for OS will be dependent on observing a significant result for rPFS.

Time from randomisation until the first of:

* Biochemical progression
* Local progression
* Pelvic Lymph node progression
* Distant metastases development or progression
* Skeletal Related Event (where confirmed disease progression)
* Death from prostate cancer

Time from randomisation to death from prostate cancer.

Cancer Research UK

Novartis

Janssen Pharmaceutica NV

University College, London

Digestive System Diseases

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pancreatic Cancer

Durvalumab

Antineoplastic Agents, Immunological

Durvalumab + Stereotactic Ablative Body Radiotherapy

Durvalumab will be given 750 mg, intravenously (IV) over 60 minutes (+/- 5 minutes), Q14 days beginning D1. Four doses of durvalumab will be administered on the Q14 day schedule. Subsequently Durvalumab will continue as maintenance 1500mg, intravenously (IV) over 60 minutes (+/- 5 minutes), Q28 days up to 1 year or until progression (11 doses), unacceptable toxicity or other reason. If a patient undergoes resection, they will resume durvalumab once appropriately healed from surgery (approximately 4-8 weeks) at discretion of treating medical oncologist.

SABR delivered as 6.6 Gy/fraction x 5 fractions given within two weeks will be administered weekdays and will begin D8.

Eileen O'Reilly, MD

The purpose of this study is to find out if combining durvalumab with standard stereotactic ablative radiotherapy (SABR) is an effective treatment for people with locally advanced or borderline resectable pancreatic cancer. The researchers will also look at the safety of the combination treatment and any side effects it causes.

Radiation Therapy in Combination With Durvalumab for People With Pancreatic Cancer

A Phase I/II Study of Durvalumab (Medi 4736) and Stereotactic Ablative Body Radiotherapy in Locally Advanced Pancreatic Adenocarcinoma

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Duration of time from diagnosis to time of progression

Based on overall downstaging of disease post-treatment

From study enrollment to time of progression

As measured from cytokine analysis from serum

As determined from flow cytometry from biopsies and blood

As determined from quantitative immunohistochemistry on biopsy samples

As determined from analysis of stool samples

AstraZeneca

Cedars-Sinai Medical Center

Memorial Sloan Kettering Cancer Center

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

SBRT to LACC following whole pelvis external beam radiotherapy

SBRT to reproduce HDR BT dose distribution in non-operated patients LACC

SBRT

Maria Inês Antunes, MD

Carlo Greco, MD

Manuela Seixas

This study will evaluate the role of SBRT with the aim to reproduce high dose rate brachytherapy (HDR BT) dose distribution by means of external beam radiotherapy in the radical treatment in patients with LACC. The study will employ devices to accurately reproduce pelvic anatomy and mitigate target motion and will make use of real-time online tracking.

This is a phase I/II feasibility study of hypofractionated, image-guided Volumetric Modulated Arc Therapy (VMAT) Stereotactic Body Radiotherapy (SBRT) to LACC with the aim to reproduce HDR BT dose distribution by means of external beam radiotherapy in the radical treatment in patients with LACC. The study will employ devices to accurately reproduce pelvic anatomy and mitigate target motion and will make use of real-time online tracking.

Eligible patients who consent to participate in the current study will receive 4 image-guided SBRT sessions to a prescription of 7 Gray per fraction to the LACC (HR-CTV) following whole pelvis external beam radiotherapy.

SBRT will start within one week after whole pelvis external beam radiotherapy. The study will enroll a total of 30 patients. After treatment, patients will be followed-up at 1 month, at 3 months (+/- 1 week), at 6 months (+/- 4 weeks), and then every 6 months (+/- 6 weeks) until the end of the 3rd year, then annually until the 5th year.

The equivalence of outcome and toxicity will be measured by comparing the data obtained in the study to literature data regarding the standard modality of brachytherapy. Patients' oncological outcomes, toxicity and quality of life data will be reported.

Patients enrolled in this study must have received or planned to receive 45 to 50 Gray in 25 fractions to pelvis with a simultaneous integrated boost (SIB) of 55 Gray in 25 fractions to metabolic active primary lesion and of 55 Gray in 25 fractions to 62.5 Gray in 25 fractions suspicious nodes of prior external beam radiation therapy. Following completion, patients will receive a boost of 28 Gray in 4 fractions using Image Guided Stereotactic Body Radiation Therapy techniques.

VIBE - Virtual Image Guided Brachytherapy Emulation for Locally Advanced Cervical Cancer (LACC)

A Phase I/II Study for Image Guided Stereotactic Body Radiation Therapy Boost for Definitive Treatment of Locally Advanced Cervical Cancer (LACC)

Fulfillment of protocol dosimetrical endpoints and constraints

anatomical accuracy will be confirmed with image guided (CBCT) and online tracking will guarantee a limit of 2mm threshold

3D deviations recorded in CBCT images and electromagnetic recording

Treatment related side effects based on CTCAE V5.0

Change from baseline in European Organisation for Research and Treatment of Cancer quality of life questionnaire C30

Change from baseline in European Organisation for Research and Treatment of Cancer quality of life questionnaire N24

Fundacao Champalimaud

Principal Investigator

Symptoms and General Pathology

Neoplasm Metastasis

Neoplastic Processes

A minimum of thirty patients will be included for each dose level. An interval of at least 24 weeks from the first patient treatment to the next patient treatment at each dose level will be respected. In the meantime, more patients will be included in the previous dose level, in an effort to establish the secondary endpoints. In case 1-5 patients present with dose-limiting toxicity (DLT) at 6 months after SABR, thirty additional patients will be included at the same dose level. The maximal tolerated dose will be defined as the dose level below which at least 10 patients present with a dose-limiting toxicity at 6 months after SABR.

Stereotactic Ablative Radiotherapy (SABR)

Piet Dirix, MD

Stereotactic ablative body radiotherapy (SABR) can be considered for patients with so-called "oligometastatic" disease. However, since this is a relatively new technique, information on the optimal scheduling is lacking. Even prospective randomized trials on SABR for oligometastases typically allow different fractionation schedules to be used. This is especially true for non-spine bone and lymph node metastases, where the literature is scarce to non-existent.

There is also emerging evidence that SABR can stimulate the immune response, by a variety of mechanisms such as increasing TLR4 expression on dendritic cells, increasing priming of T cells in draining lymph nodes, and increasing tumor cell antigen presentation by dendritic cells. Again, it is not clear which fractionation schedule elicits the most robust immune response.

Therefore, it is opportune to compare the most commonly used stereotactic regimens regarding toxicity, efficacy, and immune priming.

This trial is a non-randomized prospective phase I trial determining a regimen of choice for patients with non-spine bone and lymph node oligometastases (≤ 3 lesions). The metastatic lesion(s) must be visible on CT and \< 5 cm in largest diameter. A total of ninety patients will be consecutively included in three different fractionation regimens. They will be offered stereotactic ablative radiotherapy to all metastatic lesions in 5, 3 or 1 fractions. Dose-limiting toxicity (DLT), defined as any acute grade 3 or 4 toxicity, will be recorded as the primary endpoint. Overall acute and late toxicity, quality of life, local control, and progression-free survival are secondary endpoints.

Liquid biopsies will be collected throughout the course of this trial, i.e. at simulation, after each fraction and at 6 months after the end of the radiotherapy. Translational research will focus on assessment of circulating cytokines and flow cytometry analysis of immune cells.

* Background \& rationale

Stereotactic ablative body radiotherapy (SABR) is indicated in patients with oligometastatic, oligoprogressive, or traditionally radioresistant disease, who often present with minimal or no associated symptoms \[1, 2\]. However, since this is a relatively new technique, information on the optimal scheduling is lacking. Even prospective randomized trials on SABR for oligometastatic disease typically allow different fractionation schedules to be used \[3\]. This is especially true for non-spine bone and lymph node metastases, where the literature is scarce to non-existent and many different schedules are used, even within a single center \[4,5\].

There is also emerging evidence that SABR can stimulate the immune response, by a variety of mechanisms such as increasing toll-like receptor 4 (TLR4) expression on dendritic cells, increasing priming of T cells in draining lymph nodes, and increasing tumor cell antigen presentation by dendritic cells \[6\]. Again, it is not clear which fractionation schedule elicits the most robust immune response. For instance, in combination with cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) immunotherapy, different radiation regimens in two carcinoma models growing in syngeneic mice were compared \[7\]. Marked differences in induction of tumor-specific T cells and of an abscopal effect were observed. Each regimen had similar ability to inhibit the growth of the irradiated tumor when radiation was used alone. The addition of anti-CTLA-4, however, caused complete regression of the majority of irradiated tumors and an abscopal effect in mice receiving a hypofractionated regimen (3 fractions of 8 Gy) but not in mice treated with a single dose of 20 Gy. An additional fractionated regimen (5 fractions of 6 Gy) was tested, which showed intermediate results. This indicates that a specific therapeutic window may exist for the optimal use of radiotherapy as an immune adjuvant.

It seems an opportune moment to compare the most commonly used stereotactic regimens regarding toxicity and efficacy.

- Trial design

A minimum of thirty patients will be included for each dose level. An interval of at least 24 weeks from the first patient treatment to the next patient treatment at each dose level will be respected. In the meantime, more patients will be included in the previous dose level, in an effort to establish the secondary endpoints. In case 1-5 patients present with dose-limiting toxicity (DLT) at 6 months after SABR, thirty additional patients will be included at the same dose level. The maximal tolerated dose will be defined as the dose level below which at least 10 patients present with a dose-limiting toxicity at 6 months after SABR.

* Trial procedures

Registration of toxicity: Pre-study; last day of SABR; 3 months after SABR; 6 months after SABR; every 3 months (first year after SABR); every 6 months (second year after SABR); yearly thereafter.

Registration of QoL: Pre-study; last day of SABR; 3 months after SABR; 6 months after SABR; every 3 months (first year after SABR); every 6 months (second year after SABR); yearly thereafter.

Blood sample: every SABR fraction; 3 months after SABR; 6 months after SABR Imaging: 6 months after SABR. All imaging is considered standard and should minimally include a CT of the irradiated lesion(s) but might also include MRI and/or PET-CT (with whatever relevant tracer) if standard for that malignancy.

- Translational research

At the moment, much is unknown about the mechanism of radiotherapy and of SABR in particular. Moreover, only a few predictive biomarkers of response to radiotherapy have been suitably investigated in clinical settings and none of these biomarkers is currently employed in the clinic to assist patient, dose or schedule selection. Hence, liquid biopsies will be collected throughout the course of this study for biobanking.

An interesting measure of DNA damage in circulating tumor cells (CTCs) is γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks \[9\]. It is also becoming clear that - besides mediating cytotoxic and cytostatic effects on malignant cells - radiotherapy has multipronged immunomodulatory functions manifesting locally (within irradiated lesions) and systemically (within non-irradiated lesions and in the circulation). However, the mechanisms by which radiation induces anti-tumour T cells remain unclear. Apparently, DNA exonuclease Trex1 is induced by radiation doses above 12-18 Gy in different cancer cells, and attenuates their immunogenicity by degrading DNA that accumulates in the cytosol upon radiation. Cytosolic DNA stimulates secretion of interferon-b by cancer cells following activation of the DNA sensor cGAS and its downstream effector STING. Repeated irradiation at doses that do not induce Trex1 amplifies interferon-b production, resulting in recruitment and activation of Batf3-dependent dendritic cells \[10\]. This effect is essential for priming of CD8+ T cells that mediate systemic tumour rejection (abscopal effect). These data suggest a link between the immune-stimulatory effects of radiation and the DNA damage response.

1. Required samples

   The liquid biopsy in this study encompasses pheripheral blood samples (1x 9mL EDTA and 1x 9mL CPT tubes), to be taken at at simulation, immediately after each fraction, approximately 48 hours after the last fraction, and at 3 and 6 months follow-up for biobanking.
2. Assessment of circulating cytokines

   One EDTA blood tube generally yields 4 mL of plasma, which can be split in half for circulating free DNA (cfDNA) analysis (vide infra) and for the measurement of protein concentrations of circulating cytokines. This latter can be done using Luminex assays, and requires and input volume of 100 µL per assay, allowing 20 cytokines to be profiled using 2 mL of plasma. The plasma must be kept at -80° C. Under these conditions, most cytokines are stable for up to two years under the premises that freeze-thaw cycles are avoided \[11\].
3. cfDNA for shallow whole genome sequencing

   For cfDNA low-pass whole genome sequencing, cfDNA first needs to be extracted from plasma samples with a typical starting volume of 1 mL. The cfDNA concentrations from 1mL of plasma, in a final elution volume of 50 µL, are highly variable and depend on tumour burden (range 0.2ng/µL to 62.8ng/µL). Hence the calculated cfDNA yield from 1 mL of plasma ranges from 10 ng to 3,140 ng. For low-pass whole genome sequencing using the Thru-PLEX DNA-seq Library Kit, 2 ng of cfDNA is required, suggesting that 1 mL of plasma should be sufficient in most cases. To avoid patient drop-out due to insufficient starting material, biobanking 2 mL of plasma aliquoted in units of 400 µL at -80oC is advisable. An exemplary analysis is provided in Li et al, Mol Oncology, 2017 \[12\].
4. Flow cytometry analysis of immune cells

   Peripheral blood mononuclear cells (PBMC) can be isolated from heparinized venous blood by centrifugation on a Ficoll-Hypaque gradient within 4 h of venepuncture. The PBMCs can cryopreserved in liquid nitrogen in heat-inactivated foetal bovine serum (FBS) supplemented with 10% dimethyl sulphoxide (DMSO) until analysis. Upon analysis, cells are thawed by submersion at 37° for 1-2 minutes and resuspended in a medium containing Iscove's Modified Dulbecco's Medium (IMDM) supplemented with 20% FBS and 1% glutamine \[13\].

   - Ethics \& regulatory approval

   The trial will be conducted in compliance with the principles of the Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil, October 2013), the principles of GCP and all of the applicable regulatory requirements. The study protocol will be amended to the Ethics Committee (EC) of the GZA Hospitals, Belgium. Any subsequent protocol amendment will be submitted to the EC for approval.

   - Data handling

   All data will be prospectively collected by the clinical trials oncology (www.clinicaltrialsoncology.be) of the GZA hospitals, campus Sint Augustinus.

   - Publication policy

   Publications will be coordinated by the Principle Investigator (PD) and the co-investigators (PM \& DV). Authorship to publications will be determined in accordance with the requirements published by the International Committee of Medical Journal Editors and in accordance with the requirements of the respective medical journal.

   - Insurance/Indemnity

   In accordance with the Belgian Law relating to experiments on human persons dated May 7, 2004, Sponsor shall assume, even without fault, the responsibility of any damages incurred by a Study Patient and linked directly or indirectly to the participation to the Study, and shall provide compensation therefore through its insurance.

A Dose-escalation Trial of Stereotactic Ablative Body Radiotherapy for Non-spine Bone & Lymph Node Oligometastates

A Phase I Dose-escalation Trial of Stereotactic Ablative Body Radiotherapy (SABR) for Non-spine Bone & Lymph Node Oligometastates

The investigators will allow trial-related monitoring, audits, EC review, and regulatory inspections (where appropriate) by providing direct access to source data and other documents (i.e. patients' case sheets, blood test reports, X-ray reports, histology reports etc.). The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

To determine the maximum tolerated dose (MTD). The maximal tolerated dose will be defined as the dose level below which at least 10 patients present with a dose-limiting toxicity .

Acute toxicity will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Late toxicity will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Local response will be evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Local failure will be scored as an event if an irradiated lesion shows an increase in size of ≥20%, according to RECIST v1.1.

Progression-free survival is defined as the time from inclusion to documented disease progression according to RECISTv1.1 or any other clinically relevant definition (e.g. biochemical progression in prostate cancer) or death from any cause.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Randomised Controlled Platform Trial Testing Treatments in Metastatic Hormone Sensitive Prostate Cancer	NCT06320067	Prostate Cancer...	Stereotactic Ab... 177Lu-PSMA-617 Niraparib and A... Abiraterone Ace... Apalutamide Androgen Depriv... Androgen Recept... Local Radiother... Prednisolone Docetaxel	18 Years -	University College, London
Radiation Therapy in Combination With Durvalumab for People With Pancreatic Cancer	NCT03245541	Pancreatic Aden...	Durvalumab Stereotactic Ab...	18 Years -	Memorial Sloan Kettering Cancer Center
A Randomised Controlled Platform Trial Testing Treatments in Metastatic Hormone Sensitive Prostate Cancer	NCT06320067	Prostate Cancer...	Stereotactic Ab... 177Lu-PSMA-617 Niraparib and A... Abiraterone Ace... Apalutamide Androgen Depriv... Androgen Recept... Local Radiother... Prednisolone Docetaxel	18 Years -	University College, London
VIBE - Virtual Image Guided Brachytherapy Emulation for Locally Advanced Cervical Cancer (LACC)	NCT06394297	Cervical Cancer	SBRT	18 Years -	Fundacao Champalimaud
A Dose-escalation Trial of Stereotactic Ablative Body Radiotherapy for Non-spine Bone & Lymph Node Oligometastates	NCT03486431	Metastatic Canc...	Stereotactic Ab...	18 Years -	Cancer Research Antwerp

Spots Global Cancer Trial Database for stereotactic ablative body radiotherapy (sabr)