Clinical trial NCT05453682: Hypofractionated IMRT With Concurrent Chemotherapy in Muscle-invasive Bladder Cancer (HIRACUM)
Official title: Hypofractionated Intensity-modulated Radiation Therapy With Concurrent Chemotherapy in Musc Le-invasive Bladder Cancer:
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bladder Cancer
Keywords: bladder cancer
hypofractionated radiotherapy
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2022-07-12
Enrollment: 53
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.)

Primary outcomes:
measure: bladder preservation disease-free survival rate
timeFrame: 2 years after participation of all subjects
Secondary outcomes:
measure: 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
timeFrame: 3 months after participation
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0radiation therapy
timeFrame: 5 years after participation
measure: EORTC QOL-C30 measurement
timeFrame: 5 years after participation
measure: 2 year disease-free survival when concurrent chemo-hypofractionated intensity-modulated radiation therapy
timeFrame: 2 years after participation of all subjects
measure: overall survival when concurrent chemo-hypofractionated intensity-modulated radiation therapy
timeFrame: 5 years after participation of all subjects
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
References: