Neoplasms

Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Neoplasm Metastasis

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Methyltestosterone

Testosterone

Testosterone undecanoate

Testosterone enanthate

Testosterone 17 beta-cypionate

Pluvicto

Radiopharmaceuticals

Androgens

Hormones

Hormone Antagonists

Metastasis directed therapy with stereotactic ablative radiotherapy to all detectable sites of disease plus PSMA radiopharmaceutical therapy and discontinuation of castration

Metastasis directed therapy with stereotactic ablative radiotherapy to all detectable sites of disease plus PSMA radiopharmaceutical therapy and discontinuation of castration, followed by restoration of physiologic testosterone

stereotactic ablative radiotherapy

PSMA targeted radiopharmaceutical therapy

topical testosterone

Nicholas G Nickols, MD PhD

Matthew B Rettig, MD

Nicholas Nickols, MD

Nicholas George Nickols, MD PhD

This trial tests if the combination of comprehensive metastasis directed therapy delivered by a precision form of external beam radiotherapy (stereotactic ablative radiotherapy), combined with PSMA targeted radiopharmaceutical therapy and cessation of castration, and then followed by testosterone replacement, is an effective treatment for metastatic castration resistant prostate cancer.

All patients will be treated with stereotactic ablative radiotherapy and PSMA targeted radiopharmaceutical therapy with cessation of castration. Half of patients are randomized to either receive, or not receive, subsequent testosterone replacement.

This is a randomized, parallel-arm, two-stage open-label phase 2 study of comprehensive metastasis directed therapy in the form of stereotactic body radiation therapy (SBRT) to all detectable sites of disease plus PSMA targeted radiopharmaceutical therapy (pluvicto), discontinuation of castration, with and without testosterone replacement therapy (TRT) in metastatic castration resistant prostate cancer (mCRPC).

Randomized Phase II Trial of Targeted Radiation With no Castration for Mcrpc

Phase II Trial of Targeted Radiation With no Castration for Mcrpc

6-month radiographic progression-free survival (rPFS) measured by conventional imaging from date of initiation of PSMA radiopharmaceutical therapy

Physician reported Common Terminology Criteria for Adverse Events (CTCAE version 5.0)

EPIC-26 contains 26 items in 5 domains (Urinary Incontinence, Urinary Irritative/Obstructive, Bowel, Sexual, and Hormonal). Raw scores are transformed linearly to a 0-100 scale, with higher scores representing better HRQOL.

This is the rate of PSA response (PSA decrease by 30%, 50%, 90%), and maximal response

Time to PSA progression per PCWG3 criteria, from date of initiation of PSMA radiopharmaceutical therapy

Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) from date of initiation of PSMA radiopharmaceutical therapy

Time-to-event, Bone progression by Prostate Cancer Working Group 3 (PCWG3) criteria and/or soft tissue progression by RECIST v1.1, from date of initiation of PSMA radiopharmaceutical therapy

Measured using Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE)

Time-to-event, a composite between time to PSA progression (PCWG3) and/or radiographic progression (PCWG3 for bone, RECIST 1.1 for soft tissue), from date of initiation of PSMA radiopharmaceutical therapy

Time-to-event, from date of initiation of PSMA radiopharmaceutical therapy

FACT-P includes a general functional status scale (consisting of four subscales: physical wellbeing, social and family wellbeing, emotional wellbeing, and functional wellbeing) and a prostate-cancer-specific subscale. Total score is calculated with general function and prostate-cancer-specific scores, and ranges from 0 to 156 (higher scores indicate better functional status).

VA Office of Research and Development

Carcinoma

Urinary Bladder Neoplasms

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Fluorodeoxyglucose F18

Immunomodulating Agents

Immunologic Factors

No signs of extra-pelvic metastasis on conventional imaging (abdominopelvic and thoracic CT/MRI) and 18F-FDG-PET-CT's

No signs of extra-pelvic metastasis on conventional imaging (abdominopelvic and thoracic CT/MRI) but presence of ≤ 3 metastasis on 1 or both 18F FDG PET-CT 's

No signs of extra-pelvic metastasis on conventional imaging (abdominopelvic and thoracic CT/MRI) but presence of \> 3 metastasis on 1 or both 18F FDG PET-CT 's

Patient receives standard of care therapy with either radical cystectomy with pelvic lymph node dissection or trimodality therapy (consisting of a visible complete TURb and radio chemotherapy). Concurrently, the oligometastasis will be treated with stereotactic body radiotherapy or metastasectomy.

Metastasis directed therapy (MDT)

Patient receives standard of care therapy with either radical cystectomy with pelvic lymph node dissection or trimodality therapy (consisting of a visible complete TURb and radio chemotherapy). Afterwards immunotherapy will be initiated and regular follow up will be performed.

Immunotherapy

Patient receives standard of care therapy with either radical cystectomy with pelvic lymph node dissection or trimodality therapy (consisting of a visible complete TURb and radio chemotherapy). Afterwards regular follow up is performed.

Standard of care

Valerie Fonteyne, MD; PhD

Flor Verghote, MD

Valerie Fonteyne

Evaluate the impact of 18F-FDG-PET-CT on the staging of patients with muscle invasive bladder cancer. Based on the results of 2 18F-FDG-PET-CT's patients are stratified in non-metastatic, oligometastatic and polymetastatic bladder cancer patients and the treatment is adapted accordingly to improve overall survival.

Evaluating the Impact of 18F-FDG-PET-CT on Risk Stratification and Treatment Adaptation for Patients With Muscle Invasive Bladder Cancer

Evaluating the Impact of 18F-FDG-PET-CT on Risk Stratification and Treatment Adaptation for Patients With Muscle Invasive Bladder Cancer (EFFORT-MIBC): A Phase II Prospective Trial

Defined as the time from diagnosis of MIBC to death from any cause

Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Defined as appearance of local/locoregional recurrence diagnosed at CT-scan or cystoscopy in case of TMT or appearance of metastasis diagnosed at MIBC or non-MIBC-related imaging.

Defined as time of diagnosis until occurrence of distant metastasis on repeated imaging.

Defined as time of diagnosis until death due to MIBC.

Validated questionnaire assessing different health-related parameters (psychological, physical and social well-being) in cancer patients

Validated questionnaire assessing the health-related QOL of muscle invasive bladder cancer patients

Sensitivity/specificity of 18F-FDG-PET-CT

A biopsy specimen of the bladder, obtained after transurethral resection of the bladder (TURb),as well as urine and blood samples will be collected for validation of predictive biomarkers by evaluating the correlation between response to therapy and outcome (PFS, DMFS, DSS and OS) with in literature reported biomarkers determined on biopsy specimen of the bladder, obtained after TURb.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Randomized Phase II Trial of Targeted Radiation With no Castration for Mcrpc	NCT06084338	Prostate Cancer	stereotactic ab... Pluvicto topical testost...	18 Years -	VA Office of Research and Development
Randomized Phase II Trial of Targeted Radiation With no Castration for Mcrpc	NCT06084338	Prostate Cancer	stereotactic ab... Pluvicto topical testost...	18 Years -	VA Office of Research and Development
Randomized Phase II Trial of Targeted Radiation With no Castration for Mcrpc	NCT06084338	Prostate Cancer	stereotactic ab... Pluvicto topical testost...	18 Years -	VA Office of Research and Development
Evaluating the Impact of 18F-FDG-PET-CT on Risk Stratification and Treatment Adaptation for Patients With Muscle Invasive Bladder Cancer	NCT04724928	Muscle-Invasive...	Metastasis dire... Immunotherapy Standard of car...	18 Years -	University Hospital, Ghent

Spots Global Cancer Trial Database for metastasis directed therapy