Hypofractionated IMRT With Concurrent Chemotherapy in Muscle-invasive Bladder Cancer (HIRACUM) (HIRACOM)

Hypofractionated Intensity-modulated Radiation Therapy With Concurrent Chemotherapy in Musc Le-invasive Bladder Cancer:

The purpose of this study is to investigate the side effects, quality of life, and treatment effects of concurrent chemo-hypofractionated intensity-modulated radiation therapy in bladder cancer.

Twenty fractionation within 4 weeks are performed using hypofractionated intensity-modulated radiation therapy. As for the radiation dose, 2.8-3.2 Gy at a time, total dose 56-64 Gy, to the high-risk target volume, and 2-2.2 Gy at a time, and 40-44 Gy, respectively, to the low-risk target volume. It aims to include more than 97% of the total dose to cover the entire PTV, and the minimum dose in the PTV is not lower than 95% of the prescribed dose, and the maximum dose does not exceed 107% of the prescribed dose. Chemotherapy before and after radiotherapy can be performed depending on the institutional policy. Among radiotherapy, chemotherapy is performed with platinum-based agents (cisplatin, carboplatin, etc.), and is administered once a week for a total of 3 or more.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Radiation: hypo-IMRT

Detailed Description

For bladder cancer, conventional concurrent chemoradiotherapy is irradiated with a daily radiation dose of 1.8-2.0 Gy each, a total of 64 Gy or more, and the radiation treatment period takes more than 6 weeks in bladder preserving protocol. Concurrent chemoradiotherapy has the advantage of bladder preservation, but gastrointestinal, genitourinary, and hematologic side effects occur in about 5%. Hypofractionated radiotherapy has the advantage of increasing the radiation-biological effect on tumors by reducing the number of treatments instead of increasing the daily dose, and shortening the overall treatment time. On the other hand, hypofractionated radiotherapy can also increase the risk of side effects related to treatment because the radiologic effects on normal tissues also increase. However, the biological effect of radiation on normal tissues can be reduced by applying intensity-modulated radiation therapy in hypofractional radiation therapy to reduce radiation exposure to normal tissues. Clinical studies of concurrent chemotherapy with hypofractionation radiation therapy are still in its insignificant stage.

The purpose of this study is to investigate the side effects, quality of life, and treatment effects of concurrent chemo-hypofractionated intensity-modulated radiation therapy in bladder cancer.

The 2-year bladder conserving disease-free survival rate after the existing concurrent chemo-radiation therapy is known to be about 55%, and when concurrent chemo-hyofractionated intensity-modulated radiation therapy is performed in invasive bladder cancer, the 2-year bladder conservation disease-free survival rate is expected about 70%. The number of patients required to verify this was 80% power, a significance level of alpha = 0.1, recruitment of patients for 3 years, and taking into account the follow-up observation for 2 years after recruitment, and setting the dropout rate of 15%, a total of 53 patients was necessary.

Twenty fractionation within 4 weeks are performed using hypofractionated intensity-modulated radiation therapy. As for the radiation dose, 2.8-3.2 Gy at a time, total dose 56-64 Gy, to the high-risk target volume, and 2-2.2 Gy at a time, and 40-44 Gy, respectively, to the low-risk target volume. It aims to include more than 97% of the total dose to cover the entire PTV, and the minimum dose in the PTV is not lower than 95% of the prescribed dose, and the maximum dose does not exceed 107% of the prescribed dose. Chemotherapy before and after radiotherapy can be performed depending on the institutional policy. Among radiotherapy, chemotherapy is performed with platinum-based agents (cisplatin, carboplatin, etc.), and is administered once a week for a total of 3 or more.

• Study Type: Interventional
• Enrollment (Anticipated): 53
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Won Park, Dr; Phone Number: 82-10-9933-2616; Email: wonro.park@samsung.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients diagnosed with bladder cancer histologically
2. Patients with muscle layer involvement in transurethral resection (pT2 or higher)
3. Patients without pelvic lymph node metastasis by computed tomography (CT) or magnetic resonance images (MRI) of the pelvis.
4. Patients who want bladder conservation treatment
5. Patients over 20 years old
6. Patients with Zubrod (ECOG) performance status 0-1 within 1 week prior to participation in the study
7. Patients who have signed the consent form with sufficient information by the patient or guardian
8. Patients with hematologic findings capable of concurrent chemoradiotherapy

Exclusion Criteria:

1. Patients with previous pelvic radiotherapy history
2. Pregnant or lactating patients
3. Patients with distant metastasis
4. Patients judged to be difficult to conserve bladder due to extensive non-invasive/invasive bladder cancer
5. Patients who have not been disease-free for more than 5 years after diagnosis of cancer (excluding thyroid cancer, non-melanoma skin cancer, T1a prostate cancer, and intraepithelial cancer of the cervix)
6. Patients with untreated severe acute disease
7. Patients predicted to have a high probability of radiation complications due to connective tissue disease (lupus, scleroderma, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypo IMRT; in muscle invasive bladder cancer, hypofractionated IMRT with chemotherapy	Radiation: hypo-IMRT; Twenty fractionation within 4 weeks are performed using hypofractionated intensity-modulated radiation therapy. As for the radiation dose, 2.8-3.2 Gy at a time, total dose 56-64 Gy, to the high-risk target volume, and 2-2.2 Gy at a time, and 40-44 Gy, respectively, to the low-risk target volume.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bladder preservation disease-free survival rate	Two-year bladder preservation disease-free survival rate when concurrent chemo-hypofractionated intensity-modulated radiation therapy	2 years after participation of all subjects

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by Number of participants with treatment-related adverse events as assessed CTCAE v5.0 radiation therapy	acute toxicity	3 months after participation
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0radiation therapy	late toxicity	5 years after participation
EORTC QOL-C30 measurement	QoL	5 years after participation
2 year disease-free survival when concurrent chemo-hypofractionated intensity-modulated radiation therapy	disease-free survival	2 years after participation of all subjects
overall survival when concurrent chemo-hypofractionated intensity-modulated radiation therapy	overall survival	5 years after participation of all subjects

Collaborators and Investigators

• Sponsor: Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2021
• Primary Completion (Anticipated): December 31, 2026
• Study Completion (Anticipated): December 31, 2029

Study Registration Dates

• First Submitted: December 29, 2021
• First Submitted That Met QC Criteria: July 6, 2022
• First Posted (Actual): July 12, 2022

Study Record Updates

• Last Update Posted (Actual): July 12, 2022
• Last Update Submitted That Met QC Criteria: July 6, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: bladder cancer; hypofractionated radiotherapy
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: SMC-2021-01-026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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