Disitamab Vedotin Combined With Radiotherapy for Bladder Preservation

An Open, Single Arm, Phase II Clinical Study on the Efficacy and Safety of Bladder Sparing Therapy With Vidixizumab Combined With Local Radiotherapy in Patients With HER-2 Expressing Myometrial Invasive Urothelium Carcinoma

This is a prospective, open, single center clinical study of vidicizumab combined with local radiotherapy as bladder conserving therapy in patients with muscle invasive bladder urothelium cancer with HER-2 expression (IHC 2+or 3+). A total of 30 subjects were included in the study

Study Overview

• Status: Not yet recruiting
• Conditions: Urothelial Carcinoma
• Intervention / Treatment: Radiation: radiotherapy; Drug: Disitamab Vedotin

Detailed Description

A total of 30 subjects were included in the study. Each subject underwent diagnostic bladder resection (TURBT) and imaging diagnosis, and biological samples such as blood, urine, and biopsy tissue were collected before treatment. After myometrial invasive bladder cancer with HER2 expression (IHC 2+or 3+) judged by pathological tissue, four cycles of neoadjuvant therapy with vedixizumab (2.0mg/kg) was first performed, and then bladder conserving therapy was performed by maximizing TURBT combined with radiotherapy and chemotherapy. The patient will receive vidiximab combined with local radiotherapy after maximizing TURBT surgery. The subjects received a treatment cycle of six consecutive treatment cycles of vidixitol every two weeks, and simultaneously received one month of radiation therapy (SBRT, with a total dose of over 50 Gy in the bladder irradiation field). After completing the above treatment, tumor evaluation will be conducted through imaging and exfoliative cytology. After the completion of radiotherapy, the first tumor efficacy evaluation will be conducted. After the end of radiotherapy, tumor efficacy evaluation will be conducted every 6 weeks. Patients who are not tolerant to radiotherapy (evaluated by the researchers) will directly discontinue the medication.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: zhang xiaoping, doctor; Phone Number: 027-85726375; Email: xzhang@hust.edu.cn
• Study Contact Backup: Name: jiang guosong, doctor; Phone Number: 027-85726375; Email: 499429436@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female ≥ 18 years old;
2. ECOG PS: 0-1 points;
3. Subjects need to receive cystoscope or diagnostic electrotomy, imaging diagnosis, and the investigator judges that it is myometrial invasive bladder urothelium cancer (urothelium cancer is the main pathological component>50%), and plans to receive comprehensive treatment for bladder preservation;
4. Clinical staging T2 (CT/MRI+PET/CT);
5. Expected survival time ≥ 3 months;
6. The immunohistochemical staining result of the tissue after cystoscope or diagnostic electrotomy was IHC 2+or 3+;
7. The main organ function is normal (14 days before enrollment), which meets the following criteria:

(1) The blood routine examination standard should meet (no blood transfusion or granulocyte colony-stimulating factor treatment within 14 days before enrollment): HB ≥ 90 g/L; ANC ≥ 1.5 × 109/L; PLT ≥ 100 × 109/L; 8. Have not received systemic corticosteroid therapy within 4 weeks prior to treatment; 9. Men with reproductive ability or women with the possibility of pregnancy must use highly effective contraceptive methods during the trial process and continue to use contraception for 12 months after the end of treatment; 10. The subjects voluntarily joined the study, signed an informed consent form, had good compliance, and cooperated with follow-up.

Exclusion Criteria:

1. Those who have received other anti-tumor treatments (including corticosteroid therapy, immunotherapy) or participated in other clinical studies within 4 weeks prior to the start of research treatment, or have not yet recovered from previous toxicity (excluding 2 degree hair loss and 1 degree neurotoxicity
2. Pregnant or lactating women;
3. Positive HIV test results;
4. Active hepatitis B or C patients
5. Have a clear history of active tuberculosis;
6. Active autoimmune diseases that require systematic treatment within the past 2 years (such as the use of disease regulating drugs, corticosteroids, or immunosuppressive drugs), allowing relevant alternative treatments (such as thyroid hormone, insulin, or physiological corticosteroid replacement therapy for renal or pituitary dysfunction);
7. Other serious and uncontrollable accompanying diseases that may affect protocol compliance or interfere with the interpretation of results.
8. Urothelium carcinoma of upper urinary tract (urothelium carcinoma of renal pelvis and ureter)
9. According to the researcher's perspective, there may be increased risks associated with participating in the study, or other severe, acute, or chronic medical or mental illnesses or laboratory abnormalities that may interfere with the interpretation of the study results.

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: Disitamab Vedotin combined with radiotherapy; Disitamab Vedotin (RC48) 2.0mg/kg, once every two weeks, intravenous drip (60-90 min); Radiotherapy (SBRT, bladder irradiation field with a total dose greater than 50 Gy)

Radiation: radiotherapy; radiotherapy; Drug: Disitamab Vedotin; Four cycles of neoadjuvant therapy with Vidiximab (2.0mg/kg) were administered first, followed by bladder sparing therapy using maximized TURBT combined with radiotherapy and chemotherapy. The patient will receive vidiximab combined with local radiotherapy after maximizing TURBT surgery. The subjects received treatment with Vidixitol every two weeks for six consecutive treatment cycles, and simultaneously received 1 month of radiation therapy (SBRT, total dose of bladder irradiation field greater than 50 Gy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bladder-intact event-free survival	1-year event free survival with intact bladder	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response	Neoadjuvant therapy and postoperative pathology confirmed that the primary tumor was in complete remission (stage ypT0) and had no residual tumor cells, regardless of whether the regional lymph nodes were involved or not.	2 mouths

Collaborators and Investigators

• Sponsor: Wuhan Union Hospital, China
• Investigators: Study Director: zhang xiaoping, doctor, Huazhong University of Science and Technology Tongji Medical College Affiliated Union Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: June 12, 2023
• First Submitted That Met QC Criteria: June 20, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Physiological Effects of Drugs; Immunologic Factors; Immunoconjugates; Disitamab vedotin
• Other Study ID Numbers: UHCT221037

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: not share

Drug and device information, study documents

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