HIghly MetAstatic Life Prolonging Therapy-Resistant Prostate Cancer: Role of Stereotactic Radiotherapy for Bone and Lymph Node Metastases (HIMARS)

NCT06978296 | Not Yet Recruiting DMC

• 1 other identifier: ICO-2024-22
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose redefining this concept by focusing on volume rather than the number of metastases. To achieve this, the investigators aim to determine the Maximum Tolerated Volume (MTV) of metastatic lesions treatable with SRT (Stereotaxic radiotherapy) in a phase 1 study. In this study, the investigators will recruit patients with high-volume metastatic disease in bones or lymph nodes and progressively irradiate a volume-escalated subset of the total lesions. The selection will prioritize lesions at higher risk of causing pain or complications, such as fractures, spinal compression, or vascular compression. The investigators hypothesis is that SRT targeting multiple metastases (with a total volume ≤ MTV) will extend the duration without refractory pain and/or tumor-related complications in patients with castration-resistant and chemo-refractory prostate cancer.

Conditions

Prostate Cancer Metastatic Disease; Oligometastatic Prostate Cancer (OMPC)

Keywords

Radiotherapy; Stereotaxic; oligometastatic

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated volume (MTV)

  The MTV will be defined as the highest volume that can be treated with an acute toxicity of grade \< 3 (CTCAE V5.0 scale) in one third of patient and will allow us to determine the recommended phase II volume under the assumption that higher volumes are likely to be more toxic. The maximum tolerated Volume (MTV) is defined as the volume at which 2 Dose-Limiting Toxicity (DLT) were observed among 3 to 6 patients. DLT are considered as: * Death clearly related to irradiation * Intractable pain despite oral or intravenous opioids and/or corticosteroids (EVA \> 4 and increase of 2 from EVA baseline) * Any new grade ≥ 3 toxicity (CTCAE V5.0 scale) compared to baseline among: * Anemia * Febrile Neutropenia * Hemorrhage within grade ≥3 thrombocytopenia * Any gastro-intestinal-related disorder * Any genito-urinary-related disorder * Pneumonitis Bone marrow reserve will be determined by CT-base automatic tool.

  12 weeks

Secondary Outcomes (5)

• Number of toxicity related to radiotherapy as assessed by CTCAE v5.0

  through study completion

• Recommended volume for irradiation by SRT for phase-II

  12 weeks

• Pain relief assessed by EVA scale

  6 months

• Time to first pejorative event among tumour-related complication (bone, neurological or vascular compression) and/or death

  2 years

• Number of deceased patients

  2 years

Other Outcomes (2)

• To assess the functioning bone marrow reserve at baseline and after SRT

  Baseline and 3 months after start of SRT

• To compare the anatomical and functioning assessment of the bone marrow reserve

  Baseline and 3 months after start of SRT

Study Arms (1)

stereotaxic radiotherapy

EXPERIMENTAL

This volume escalation will be performed until MTV is reached. Level cohort is defined by: volume level Irradiation volume / Bone Marrow Reserve as below: level -1: 20% level 1 (start level): 30% level 2: 40% level 3: 50%

Radiation: Stereotactic body radiotherapy (SBRT)

Interventions

Stereotactic body radiotherapy (SBRT) RADIATION

The acceptable regimens are: * 27 Gy / 3 fractions / 3 fractions per week * 35 Gy / 5 fractions / 3 fractions per week An interval of at least 24 hours should be kept between two consecutive fractions. Prescription must be defined on 80% isodose or higher, maximum dose up to 130% of the isodose prescription. At least 90% of the Planning Target Volume should receive the prescribed dose. A coverage of \<90% of the Planning Target Volume will be considered as acceptable deviation, and coverage of \<80% of the target volume as an Unacceptable Deviation. At least 90% of the Gross Tumoral Volume should receive the prescribed dose. Only a part of the Gross Tumoral Volume\_Total could be considered for radiation, depending on the ratio with Bone Marrow Reserve. High-risk and/or symptomatic metastases will be prioritized over other metastases. Anatomic bone marrow reserve (BMR) will be first determined for each patient: BMR = Total trabecular bone - (Total trabecular bone ∩ GTV\_Total)

stereotaxic radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic prostate cancer with clinical progression after the use of androgen-receptor pathway inhibitor, chemotherapy or any other life-prolonging therapy. Patient could have been treated previously by RadioLigand Therapy (RLT).
• Performance Status \< 3
• Bone and/or lymph node metastases based on conventional (CT and bone scan) or metabolic imaging
• Bone and/or lymph node metastases suitable for SRT, according to the investigator
• Adequate organ function:
• Absolute Neutrophil Count (ANC) ≥ 1000/mm3 or
• Platelet Count ≥ 50 000/mm3 or
• Haemoglobin ≥ 8 g/dL (allowing transfusion or other intervention to achieve this minimum haemoglobin)
• Age ≥ 18 years at time of study entry
• Written informed consent obtained from the patient prior to performing any protocol-related
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Patient has valid health insurance
• Life time expected \> 3 months

You may not qualify if:

• Evidence of symptomatic metastases to the lungs, brain, peritoneum or liver
• Evidence of diffuse metastatic spread to the bone marrow (e.g. positive super bone scan) or the cerebral spinal fluid as per bone scan (no lumbar puncture required).
• Evidence of presence of symptomatic spinal cord compression with indication of neurosurgical decompression.
• Patient with symptomatic and/or high-risk tumor volume-to-bone marrow reserve ratio \> 50%
• Concurrent enrolment in another clinical study, unless it is a non-therapeutic clinical study
• Mental impairment (psychiatric illness/social situations) that may compromise the ability of the patient to give informed consent and comply with the requirements of the study;
• Patient who has forfeited his/her freedom by administrative or legal award or who is under guardianship;
• Patients unable to undergo medical follow-up in the study for geographical, social or psychological reasons.
• History of another primary malignancy except for
• Malignancy treated with curative intent and with no known active disease ≥2 years before the first dose of SRT and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• Uncontrolled pain that contraindicates patient positioning on the radiotherapy table according to investigator
• Patient indicated to or currently treated by cytopenic treatment as chemotherapy or RadioLigand Therapy
• Patient under concomitant treatment that may generate severe gastro-intestinal disorder or genito-urinary disorder

Sponsors & Collaborators

• Institut Cancerologie de l'Ouest: lead

Study Sites (1)

ICO

Saint-Herblain, 44805, France

Location

MeSH Terms

Interventions

Radiosurgery

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Loïg Vaugier, MD

  ICO

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Loïg Vaugier, MD

CONTACT

+33240679900; loig.vaugier@ico.unicancer.fr

Lucie Labarre

CONTACT

lucie.labarre@ico.unicancer.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a monocentric prospective level volume escalation phase I study of radiotherapy on oligometastasis.

Study Record Dates

• First Submitted: April 30, 2025
• First Posted: May 18, 2025
• Study Start: January 15, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): July 1, 2029
• Last Updated: December 8, 2025

Record last verified: 2025-06

Locations

FR (1)