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NCT Number: NCT07591051

Weekly Online CT or MR Adaptive Definitive SBRT for Very High Risk Localized or Regionally Metastatic Prostate Cancer

This interventional prospective multicenter international study will include 54 patients with very high-risk localized (cN0 cM0) or regional (i.e. cN1 cM0) prostate cancer according the NCCN criteria.

Patients will be treated with weekly CT or MR-informed online adaptive SBRT of the prostate and elective pelvic lymph nodes with 5 x 5 Gy. In the case of regional lymph nodes, a simultaneous integrated boost (SIB) of involved lymph nodes will be performed with 5 x 6.5 Gy. In the case of up to 2 dominant intraprostatic lesion (DIL) a SIB of the DIL with 5 x 9 Gy can be performed (optional). Importantly, coverage of these DIL volumes must be compromised as needed to respect OAR constraints.

This study is classified as risk category A according to ClinO, Art. 61, as stereotactic radiotherapy (SBRT) for localized or regional prostate cancer has been extensively evaluated in prospective interventional trials and is considered an established therapeutic modality.

Weekly CT- or MR-guided online adaptive SBRT to the prostate and elective pelvic lymph nodes with 5 × 5 Gy is, however, not yet routinely implemented for this specific patient population.

A diagnostic high field MRI during radiotherapy, e.g. week 3 is optional.

Follow-up is also according to standard of care (except for patient reported outcome measure using QLQ-C30 and QLQ-PR25 and a diagnostic MRI at 9 months after SBRT (optional), and 12 months in the case of an image non-complete response at 9 months (optional).

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Key information

Conditions

Prostate Cancer Genital Diseases Genital Diseases, Male Genital Neoplasms, Male Male Urogenital Diseases Neoplasms Neoplasms by Site Prostatic Diseases Prostatic Neoplasms Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

University Clinic Heidelberg, Heidelberg, Baden-Würtemberg, Germany

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

include:

  • Very high risk localized defined (cN0) according to NCCN guidelines consisting of ≥2 of the following:
  • cT3 disease and/or
  • Gleason 8-10 and/or
  • PSA ≥40 (the baseline PSA value should be doubled for PSAs taken while on 5-alpha reductase inhibitors) OR
  • Regionally metastatic prostate cancer (cN1, any T, any Gleason, any PSA) according to NCCN guidelines consisting of ≤3 lymph node metastases of any of the following:
  • Obturator
  • Internal iliac (hypogastric)
  • External iliac nodes
  • Presacral nodes
  • Common iliac (below iliac bifurcation)
  • Periprostatic/Perivesical AND
  • Good to moderate performance status (WHO 0-2)
  • Written informed consent.
  • A PSMA PET and multiparametric MRI is mandatory according to staging guidelines.
  • Age ≥ 18 years

Exclusion criteria

include:

  • ≥4 regional lymph nodes
  • Patients with cT4 disease (tumor is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles, and/or pelvic wall)
  • Previous RT to the pelvis or prostate
  • Previous radical prostatectomy
  • Large body size that would not fit into the MRI-simulator bore
  • Presence of distant metastases (i.e. cM1)
  • Non-regional lymph nodes (M1a):
  • Common iliac
  • Para-aortic / retroperitoneal
  • Inguinal
  • Mediastinal or supraclavicular
  • Mesorectal
  • Other
  • Bone metastases (M1b)
  • Other sites (M1c)
  • Contraindications to CT or MR-adaptive SBRT (e.g., pacemakers, severe claustrophobia).
  • Severe comorbidities that may interfere with treatment or follow-up (e.g. inflammatory bowel disease)
  • Significant concomitant diseases (e.g. hepatic dysfunction, cardiovascular disease, etc.);
  • Inability to follow procedures or insufficient knowledge of project language, inability to give consent.
  • Participation in a clinical trial, which might influence the results of this project.
  • Enrolment of the investigator, his/her family members, employees and other dependent persons.
  • Severe GU or GI symptoms (e.g., recent urinary retention or diarrhea ≥ grade 3 or obstipation to CTCAE v.5.0).
  • Severe urinary symptoms (prostate volume >60mL and/or IPSS >12)

Treatment and study plan

weekly CT or MR online adaptive definitive SBRT

Device

Patients will be treated with weekly CT or MR-informed online adaptive SBRT of the prostate and elective pelvic lymph nodes with 5 x 5 Gy. In the case of regional lymph nodes, a simultaneous integrated boost (SIB) of involved lymph nodes will be performed with 5 x 6.5 Gy. In the case of up to 2 dominant intraprostatic lesion (DIL) a SIB of the DIL with 5 x 9 Gy can be performed (optional). Importantly, coverage of these DIL volumes must be compromised as needed to respect OAR constraints.

Primary outcomes

  1. Feasibility- a successful delivery of CT or MR-informed SBRT per fraction

    Time frame: from Day 1 of treatment up to 7 weeks until end of treatment

    Feasibility will be assessed by recording whether each fraction of stereotactic body radiation therapy (SBRT), guided by computed tomography (CT) or magnetic resonance (MR) imaging, is successfully delivered according to the planned treatment parameters. Successful delivery is defined as completion of the planned fraction without protocol deviations or technical interruptions. Data will be summarized as the proportion of fractions successfully delivered per patient and overall. Every treatment fraction having passed the point of entry into the adaptive workflow will be analyzed for this endpoint.

  2. Safety - Adverse events

    Time frame: ≥ 3 months to within 1 year after completion of SBRT

    The presence of genitourinary or gastrointestinal toxicity of grade ≥ 3 within 1 year after completion of radiotherapy (according to CTCAE v5.0). Treatment-related discontinuation. and Subgroup analyses will be performed for patients with and without regional lymph node metastases (i.e., cN0 versus cN1).

Secondary outcomes

  1. Biochemical progression-free survival

    Time frame: from Day 1 up to 5 years after treatment

    This will be determined from the start of therapy until the occurrence of PSA recurrence according to the Phoenix criteria i.e. post- therapeutic PSA nadir + 2 ng/ml

  2. Castration-resistant free survival

    Time frame: from Day 1 up to 5 years after treatment

    Castration-resistant free survival defined as cancer progression despite low (castrate) levels of testosterone (<50 ng/dL). Cancer progression is defined as:

    • Biochemical progression: ≥2 consecutive PSA rises (at least 1 week apart)
    • Radiologic progression: appearance of new lesions on imaging

  3. Patients Quality of Life EQ-5D-5L from the European Organisation for Research and Treatment of Cancer

    Time frame: from Day 1 up to end of study until 5 years

    Quality-of-life will be measured using the EQ-5D-5L questionnaire during and after treatment

    All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.

  4. Patients Quality of Life QLQ-C30 from the European Organisation for Research and Treatment of Cancer

    Time frame: From Day 1 up to end of study (up to 5 years)

    Quality of life will be measured using the EORTC QLQ-C30 questionnaire. This instrument includes functional scales, symptom scales, and a global health status/quality-of-life scale. All scores are linearly transformed to a 1-4 scale. For functional scales and global health status, higher scores indicate better functioning or quality of life, whereas for symptom scales/items, higher scores indicate greater symptom burden.

  5. Adverse events

    Time frame: from Day 1 until 5 years or end of Study

    Genitourinary and Gastrointestinal toxicity measured with Common Terminology Criteria for Adverse Events (CTCAE)

  6. Patients overall survival

    Time frame: from Day 1 until Progression or death whichever comes first until 5 years

    defined from the start of therapy until death or censoring

  7. Patient overall treatment - Patient treatment workflow duration (time from MRI scan start to completion of treatment)

    Time frame: from Day 1 start of therapy, weekly until end of treatment up to 7 weeks

    Patient will be asked from the start and end of MRI scan to start and end of treatment respectively, and for all steps from simulation to treatment delivery individually

  8. Other Toxicities

    Time frame: Day 1 of Treatment for up to 5 years or until death whichever comes first

    Treatment-related toxicities other than the primary toxicity outcomes will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Other Toxicities will be evaluated during SBRT treatment and throughout follow-up for up to 5 years after completion of treatment or until patient death, whichever occurs first. The type, frequency, and severity (grade) of adverse events will be recorded according to CTCAE v5.0 criteria.

  9. Dosimetry difference

    Time frame: from Day 1 of treatment start until end of treatment up to 7 Weeks

    Dosimetry difference of the online adaptive plan compared to the original plan recalculated on the imaging of the day. Dosimetry difference is defined as difference in coverage of the planning target volume (PTV) or of one of the organs at risk e.g. bowel or rectum

  10. Anatomy changes assessed on magnetic resonance imaging (MRI)

    Time frame: from Day 1 of treatment up to 7 weeks

    Anatomical changes will be evaluated using serial magnetic resonance imaging (MRI) acquired during treatment and follow-up. Changes in relevant anatomical structures (e.g., target volume and surrounding organs at risk) will be assessed by comparing images obtained at baseline and subsequent imaging time points. Observed anatomical variations will be documented and summarized descriptively.

  11. Comparison of Patient treated and not treated

    Time frame: from Day 1 until 5 Years of study or death

    Comparison of number of patients not treated at all/not treated with all planned fractions in the CT or MR-informed workflow compared to those intended to be treated and categorization of patterns of failure within the CT or MR-informed workflow.

  12. Patient compliance

    Time frame: from Day 1 until 5 Years / end of Study

    Patient compliance will be measured by tracking a scheduled treatment sessions and adherence to the prescribed treatment protocol, including completion of all required procedures and instructions. Data will be collected throughout the treatment period and summarized as the proportion of scheduled sessions attended and procedures completed, as well as reasons for any missed sessions or deviations from the protocol.

  13. Patient well being and comfort

    Time frame: from Day 1 of treatment to weekly up to 7 weeks

    Patients will be asked to report their comfort during and after simulation assess with a 0 to 10 numerical rating scales, with 0 representing complete absence of clinical confidence to 10 representing extreme clinical confidence

  14. Physician decision certainty

    Time frame: from Day1 of treatment to weekly up to 7 weeks

    clinicians will be asked to report their clinical confidence with a 0 to 10 NRS, with 0 representing complete absence of clinical confidence to 10 representing extreme clinical confidence

Study contacts

Contact information is provided by the study sponsor or research team.

Radiation Oncology Study Office

CONTACT

[email protected]

+41432534308

Sponsors and collaborators

Lead sponsor

University of Zurich

Other

Registry information

Official study title

Weekly Online CT or MR Adaptive Definitive SBRT for Very High Risk Localized or Regionally Metastatic Prostate Cancer (HARP)

Acronym: HARP

Important dates

Study start
2026
Primary completion
2028
Study completion
2033
First posted
May 15, 2026
Registry last updated
May 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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