Adjuvant Radiotherapy and Combined Adjuvant Treatment Strategy for UTUC

Urothelial Carcinoma Clinical Trial

Official title:

Safety and Efficacy of Adjuvant Radiotherapy and Combined Adjuvant Treatment Strategy for Upper Tract Urothelial Carcinoma: An Ambispective Cohort Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06120374
• Other study ID #: LUXUS2.0
• Status: Recruiting
• Start date: October 30, 2023
• Est. completion date: October 30, 2028

Study information

• Verified date: November 2023
• Source: Peking University First Hospital
• Contact: Xuesong Li, M.D.
• Phone: +86-15801399116
• Email: pineneedle[@]sina.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is an ambispective cohort observational study to analyze the efficacy of surgery alone versus postoperative adjuvant therapy (postoperative radiotherapy/postoperative chemotherapy(immunotherapy)/ combined strategy) in patients with the upper urinary tract urothelial carcinoma with high-risk factors (postoperative pathology suggestive of pT2 and above, N+, G3/high-grade and multiple tumors, positive cut margins). A subgroup analysis was performed to obtain the population of patients who might benefit from different treatment approaches. Patients with high risk factors for postoperative recurrence or metastasis will be treated with relevant adjuvant therapy, which in turn will benefit patients.

Description:

This study is an ambispective cohort observational study to analyze the efficacy of surgery alone versus postoperative adjuvant therapy (postoperative radiotherapy/postoperative chemotherapy(immunotherapy)/ combined strategy) in patients with the upper urinary tract urothelial carcinoma with high-risk factors (postoperative pathology suggestive of pT2 and above, N+, G3/high-grade and multiple tumors, positive cut margins). A subgroup analysis was performed to obtain the population of patients who might benefit from different treatment approaches. Patients with high risk factors for postoperative recurrence or metastasis will be treated with relevant adjuvant therapy, which in turn will benefit patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: October 30, 2028
• Est. primary completion date: October 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1. Confirmed pathologic diagnosis as upper urinary tract urothelial carcinoma(UTUC), without any serious complication; 2. Meet any of the following conditions: >= pT2,pN+,tumor G3 grade, multifocality or positive surgical margins (according to AJCC 8th edition); 3. Aged >= 18 years old;

Exclusion Criteria:

• 1. Distant metastases already found at the time of surgery; non-R0 resected patients;

2. History of pelvic and abdominal radiotherapy; history of inflammatory bowel disease; history of systemic chemotherapy; 3. Pregnant or lactating women; or women of childbearing potential who are not using reliable contraception; 4. History of malignant tumors (except skin cancer that is not malignant melanoma and in situ cervical cancer, tumors that have been cured for more than 5 years); 5. Weight loss > 10% within 6 months; 6. Existing or coexisting bleeding disorders, active infection;

7. Clinically significant cardiac disease (e.g., hypertension controlled with medications, unstable angina, New York Heart Association (NYHA) >= Class II congestive heart failure, unstable symptomatic arrhythmia, or >=Class II peripheral vascular disease); 8. Those who are unable to sign informed consent due to psychological, family, social and other factors.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

Radiation:
• Radiotherapy
For participants eligible for enrollment, radiotherapy was started within 4-6 weeks after surgery. Rotational intensity-modulated radiotherapy (VMAT) with daily image-guided radiotherapy (Daily IGRT) technique was used. Range of irradiation (patients were randomized into two groups - expanded field irradiation group and involved field irradiation group)

Drug:
• Chemotherapy and immunotherapy
For patients eligible for enrollment, postoperative adjuvant chemotherapy was initiated at about 4-6 weeks after surgery, for a total of 4 cycles, with the chemotherapy regimen of gemcitabine + cisplatin. Administration: Gemcitabine 1,000 mg/m2 on days 1 and 8 (completed within 30-60 minutes), cisplatin 70 mg/m2 on day 1. Immunotherapeutic agents include (PD-1/PD-L1) to be used every 21 days postoperatively for one year.

Combination Product:
• Combined adjuvant therapy
For patients eligible for enrollment, sequential adjuvant radiotherapy (same as the radiotherapy group) and systemic drug therapy (same as the chemotherapy group; immunotherapy drugs can be PD-1 or PDL-1) can be started at about 4-6 weeks after surgery. The specific dose of drugs can be adjusted according to the actual tolerability of the patient, such as reducing or replacing the regimen, or interrupting the regimen.

Locations

Country	Name	City	State
China	Departmeng of Urology, Peking University First Hospital	Beijing
China	Department of Medical Oncology, Peking University First Hospital	Beijing
China	Department of Radiotherapy Oncology, Peking University First Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University First Hospital

Country where clinical trial is conducted

China, 

References & Publications (4)

Birtle A, Johnson M, Chester J, Jones R, Dolling D, Bryan RT, Harris C, Winterbottom A, Blacker A, Catto JWF, Chakraborti P, Donovan JL, Elliott PA, French A, Jagdev S, Jenkins B, Keeley FX Jr, Kockelbergh R, Powles T, Wagstaff J, Wilson C, Todd R, Lewis R, Hall E. Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial. Lancet. 2020 Apr 18;395(10232):1268-1277. doi: 10.1016/S0140-6736(20)30415-3. Epub 2020 Mar 5. — View Citation

Li X, Cui M, Gu X, Fang D, Li H, Qin S, Yang K, Zhu T, Li X, Zhou L, Gao XS, Wang D. Pattern and risk factors of local recurrence after nephroureterectomy for upper tract urothelial carcinoma. World J Surg Oncol. 2020 May 30;18(1):114. doi: 10.1186/s12957 — View Citation

Li X, Li H, Gao XS, Fang D, Qin S, Zhang Z, Zhou L, Li X, Wang D. Effectiveness of adjuvant radiotherapy for high recurrence risk patients with upper tract urothelial carcinoma. Urol Oncol. 2022 Sep;40(9):410.e1-410.e10. doi: 10.1016/j.urolonc.2022.03.006 — View Citation

Seisen T, Krasnow RE, Bellmunt J, Roupret M, Leow JJ, Lipsitz SR, Vetterlein MW, Preston MA, Hanna N, Kibel AS, Sun M, Choueiri TK, Trinh QD, Chang SL. Effectiveness of Adjuvant Chemotherapy After Radical Nephroureterectomy for Locally Advanced and/or Positive Regional Lymph Node Upper Tract Urothelial Carcinoma. J Clin Oncol. 2017 Mar 10;35(8):852-860. doi: 10.1200/JCO.2016.69.4141. Epub 2017 Jan 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	AE	Adverse effects	Peri-therapeutic period
Primary	PFS	Progression-free Survival	1-year, 3-year and 5-year
Secondary	OS	Overall survival	1-year, 3-year and 5-year
Secondary	CSS	Cancer specific survival	1-year, 3-year and 5-year
Secondary	LRFS	Local recurrence free survival	1-year, 3-year and 5-year
Secondary	MFS	Metastasis free survival	1-year, 3-year and 5-year
Secondary	IRFS and CRFS	intravesical-recurrence free survival and contralateral-recurrence free survival	1-year, 3-year and 5-year