Complete Local Response to Neoadjuvant Chemotherapy in Patients With Muscle Invasive Bladder Cancer Evaluated by 15O-H2O PET/MR (MAINTAIN)

Treatment of localized muscle invasive bladder cancer (MIBC) is radical cystectomy. Neoadjuvant chemotherapy (NAC) improves survival.

Approximately 50-60% of all MIBC patients undergoing NAC before cystectomy are histopathological without remnant tumor in the cystectomy specimen (T0). However, there is currently no optimal method to evaluate whether the patient is true T0 or has remnant tumor in need for consolidating radical treatment. The study aim is to investigate if 15O-H2O PET/MR can predict complete local response to neoadjuvant chemotherapy in patients with MIBC and thereby identify potential candidates for organ preservation.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Radiation: 15O-H2O PET/MR

Detailed Description

For patients with MIBC treated with NAC and radical cystectomy there is currently no good way of evaluating whether the patient is true T0 or has remnant tumor in need for consolidating radical treatment. Methods for better selection of patients that potentially can avoid cystectomy is therefore needed.

15O-labeled water (H2O) is the gold standard for PET quantification of regional tissue perfusion. 15O-H2O has been validated as a freely diffusible tracer for measuring perfusion in the myocardium and cerebral blood flow and 15O-H2O PET is the golden standard for noninvasive imaging to quantify tumor blood flow (TBF).

Method: Patients scheduled for NAC followed by radical cystectomy due to histologically documented MIBC stage cT2-4a in the urinary bladder will be included. A 15O-H2O PET/MR scan will be performed at time of inclusion (baseline) and again after NAC prior to cystectomy.

Hypothesis: We hypothesize that changes in tumor architecture and perfusion estimated with 15O-H2O PET/MR measurements and clinical evaluation during NAC can identify patients with complete local response to chemotherapy and therefore select patients to avoid radical cystectomy.

Perspectives: This study will be the first to use 15O-H2O as tracer in bladder cancer. If proven efficient, evaluation of patients undergoing NAC with 15O-H2O PET/MR could potentially safely select patients for a true bladder sparring approach and potentially give some patients the choice of chemotherapy monotherapy, or in combination with other systemic oncological treatments like immunotherapy. If successful, this should be followed by randomized studies to document the clinical benefit and potentially reduce cost and increase quality of life by safely selecting patients for bladder sparring treatment of bladder cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jørgen Bjerggaard Jensen, Professor, consultant, MD; Phone Number: 004578452617; Email: bjergaard@skejby.rm.dk
• Study Contact Backup: Name: Stefanie Korsgaard Körner, MD; Phone Number: 004530915431; Email: stkoer@rm.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Recruiting
    • Department of Urology, Aarhus University Hopsital
    • Contact: Jørgen Bjerggaard Jensen, Professor, consultant, MD; Phone Number: 004578452617; Email: bjerggaard@skejby.rm.dk
    • Contact: Stefanie Kosgaard Körner, MD; Phone Number: 004530915431; Email: stkoer@rm.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of MIBC stage cT2-4a.
• Preoperative PET/CT of thorax, abdomen, and pelvis with no suspicion of organ metastases or lymph node metastasis outside the surgical field.
• ≥18 years of age at the time of signing the Informed Consent Form. Renal function of eGFR > 60 ml/min/1,73 m2.
• Physically fit for NAC.
• Clinical decision with patient accept of NAC before cystectomy.
• Mentally healthy. Signed Informed Consent Form.

Exclusion Criteria:

- Unfit for MRI:

• Claustrophobia.
• Problems with seating arrangements (e.g. pain or involuntary movement).
• Maximal shoulder width larger than 55 cm.
• Circumference larger than 160 cm.
• Weight above 250 kg.
• Metallic implants or other metallic foreign bodies.
• Pacemaker, ICD, or pace electrodes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 15O-H2O PET/MR; All included patients will have two 15O-H2O PET/MR scan performed.	Radiation: 15O-H2O PET/MR; All included patients will have a 15O-H2O PET/MR scan performed at baseline and a scan performed after NAC, prior to cystectomy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in tumor blood flow	Change in Tumor Blood Flow (TBF) measured on 15O-H2O PET/MR as a marker of response to NAC correlated with histopathological findings in the cystectomy specimen.	Comparison of scan made 1 week before NAC compared to scan 2 weeks after NAC

Collaborators and Investigators

• Sponsor: Jørgen Bjerggaard Jensen

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 27, 2020
• Primary Completion (ANTICIPATED): March 31, 2023
• Study Completion (ANTICIPATED): March 31, 2023

Study Registration Dates

• First Submitted: March 11, 2020
• First Submitted That Met QC Criteria: March 24, 2020
• First Posted (ACTUAL): March 25, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 28, 2021
• Last Update Submitted That Met QC Criteria: July 27, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Tumor blood flow; magnetic resonans imaging; 15O water PET
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: Maintain

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No