Multi-parameter Magnetic Resonance Imaging Guides Precise Treatment of Urothelial Carcinoma

Bladder Cancer Clinical Trial

Official title:

Multi-parameter Magnetic Resonance Imaging for Early Evaluation of the Efficacy of Neoadjuvant Chemotherapy With Modified GC Regimen for Urothelial Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04588168
• Other study ID #: 2020-SR-252
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2018
• Est. completion date: June 2026

Study information

• Verified date: September 2020
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: Yuan Baorui
• Phone: +86 18351998926
• Email: yuanbr960720[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Purpose：To evaluate whether immediate multiparametric MRI evaluate the sensitivity of modified neoadjuvant chemotherapy early in patient with muscle invasive bladder cancer（MIBC）.

Rationale：Multiparametric MRI may help detect the early changes of bladder cancer receiving neoadjuvant chemotherapy.

Description:

Objective

Primary: To evaluate whether multiparametric MRI can determine the sensitivity of modified neoadjuvant chemotherapy early in patient with muscle invasive bladder cancer（MIBC）.

Secondary：To determine whether multiparametric MRI can predict the prognosis of modified neoadjuvant chemotherapy early in patient with muscle invasive bladder cancer.

Patients may receive neoadjuvant chemotherapy (typically three 21-day courses of modified gemcitabine-cisplatin(GC) therapy) followed by radical cystectomy and lymph node dissection.

Patients with primary bladder cancer or recurrence which is confirmed by pathology of previous biopsy or TURBT, undergo a multiparametric MRI(mpMRI) at baseline to stage the primary tumor. The mpMRI includes T2-weighted MRI, diffusion-weighted imaging, and dynamic contrast enhancement, which will be given a five-point VI-RADS（Vesical Imaging-Reporting And Data System） score by two radiologists specialized in urogenital radiology. Patients considered NMIBC（Non-muscle invasive bladder cancer） with mpMRI will be given TURBT, while patients with MIBC（Muscle invasive bladder cancer）will receive radical cystectomy and lymph node dissection after three 21-day courses of modified gemcitabine-cisplatin neoadjuvant chemotherapy. Patients also undergo an immediate mpMRI scan after one, two, and three cycles of neoadjuvant chemotherapy.

Specimens from the radical cystectomy are then examined by the pathology department as standard routine.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically confirmed primary or recurrent bladder cancer.

• Planned to undergo transurethral resection of bladder tumor (TURBT) or modified GC regimen neoadjuvant chemotherapy plus radical total cystectomy.

• 18 years old and older.

• Willing to give valid written informed consent.

• No contraindications to the MRI(magnetic resonance imaging) and MRI contrast agent.

Exclusion Criteria:

• Abnormal liver function (1.5 times higher than normal).

• Glomerular filtration rate < 60ml /min·kg.

• Heart failure.

• Acute myocardial infarction.

• Severe heart and lung disease.

• Hypotension and hypoxia.

• Brain metastases, or other known central nervous system metastases.

• A history of severe central nervous system diseases, including unexplained loss of consciousness or transient ischemic attack.

• Known congenital or acquired immunodeficiency, active hepatitis, active tuberculosis and other active infections, etc.

• Pregnant or lactating women.

• Patients participating in other drug trials.

• Patients with poor general condition (eg malnutrition, dehydration). Behavioral status score (ZPS quintile) = 2.

• Patients with previous autoimmune diseases or existing autoimmune diseases. (including controlled or uncontrolled drugs).

• Patients undergoing organ transplantation (transplantation of liver, kidney, heart, lung and other organs) or those who require long-term administration of immunosuppressive agents due to personal conditions.

• Those who are intolerant or allergic to cytotoxic chemotherapeutic drugs.

• Bone marrow transplantation, severe leukopenia.

• Patients with severe infection or trauma.

• Any condition based on the investigation's clinical judgment that the patient is not suitable for completing this study (such as not meeting the patient's most beneficial treatment, patient compliance, etc.)

Related Conditions & MeSH terms

• Bladder Cancer
• Carcinoma, Transitional Cell
• Urinary Bladder Neoplasms

Intervention

Drug:
• Chemotherapy
Patients with muscle invasive bladder cancer will receive modified gemcitabine-cisplatin neoadjuvant chemotherapy prior to radical cystectomy for a period of two months (three 21 day cycles) as part of standard clinical routine.

Diagnostic Test:
• Immediate Multiparametric MRI
Within 24 hours after the use of cisplatin during the first course of modified GC neoadjuvant chemotherapy, patient considered muscle invasive bladder cancer with baseline mpMRI will receive an immediate mpMRI scan.

Procedure:
• Cystectomy and Lymphadenectomy
The patient with muscle invasive bladder cancer will undergo radical cystectomy and pelvic lymph node dissection followed by a urinary tract reconstruction.

Diagnostic Test:
• conventional Multiparametric MRI
After two and three course of neoadjuvant chemotherapy, patient considered muscle invasive bladder cancer with baseline mpMRI will receive a conventional mpMRI scan.
• Baseline Multiparametric MRI
Patient considered muscle invasive bladder cancer will receive a baseline mpMRI scan within one week before neoadjuvant chemotherapy.

Locations

Country	Name	City	State
China	The first affiliated hospital of Nanjing Medical University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital with Nanjing Medical University

Country where clinical trial is conducted

China, 

References & Publications (14)

Bellmunt J, Mottet N, De Santis M. Urothelial carcinoma management in elderly or unfit patients. EJC Suppl. 2016 Mar;14(1):1-20. doi: 10.1016/j.ejcsup.2016.01.001. Epub 2016 Mar 22. — View Citation

Dash A, Galsky MD, Vickers AJ, Serio AM, Koppie TM, Dalbagni G, Bochner BH. Impact of renal impairment on eligibility for adjuvant cisplatin-based chemotherapy in patients with urothelial carcinoma of the bladder. Cancer. 2006 Aug 1;107(3):506-13. — View Citation

Galsky MD, Hahn NM, Rosenberg J, Sonpavde G, Hutson T, Oh WK, Dreicer R, Vogelzang N, Sternberg C, Bajorin DF, Bellmunt J. A consensus definition of patients with metastatic urothelial carcinoma who are unfit for cisplatin-based chemotherapy. Lancet Oncol. 2011 Mar;12(3):211-4. doi: 10.1016/S1470-2045(10)70275-8. — View Citation

Galsky MD, Pal SK, Chowdhury S, Harshman LC, Crabb SJ, Wong YN, Yu EY, Powles T, Moshier EL, Ladoire S, Hussain SA, Agarwal N, Vaishampayan UN, Recine F, Berthold D, Necchi A, Theodore C, Milowsky MI, Bellmunt J, Rosenberg JE; Retrospective International Study of Cancers of the Urothelial Tract (RISC) Investigators. Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer. Cancer. 2015 Aug 1;121(15):2586-93. doi: 10.1002/cncr.29387. Epub 2015 Apr 14. — View Citation

Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, Crawford ED. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003 Aug 28;349(9):859-66. Erratum in: N Engl J Med. 2003 Nov 6;349(19):1880. — View Citation

Hayashi N, Tochigi H, Shiraishi T, Takeda K, Kawamura J. A new staging criterion for bladder carcinoma using gadolinium-enhanced magnetic resonance imaging with an endorectal surface coil: a comparison with ultrasonography. BJU Int. 2000 Jan;85(1):32-6. — View Citation

International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group; Australian Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; Finnbladder; Norwegian Bladder Cancer Study Group; Club Urologico Espanol de Tratamiento Oncologico Group, Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011 Jun 1;29(16):2171-7. doi: 10.1200/JCO.2010.32.3139. Epub 2011 Apr 18. — View Citation

Kim TJ, Cho KS, Koo KC. Current Status and Future Perspectives of Immunotherapy for Locally Advanced or Metastatic Urothelial Carcinoma: A Comprehensive Review. Cancers (Basel). 2020 Jan 13;12(1). pii: E192. doi: 10.3390/cancers12010192. Review. — View Citation

Panebianco V, Narumi Y, Altun E, Bochner BH, Efstathiou JA, Hafeez S, Huddart R, Kennish S, Lerner S, Montironi R, Muglia VF, Salomon G, Thomas S, Vargas HA, Witjes JA, Takeuchi M, Barentsz J, Catto JWF. Multiparametric Magnetic Resonance Imaging for Bladder Cancer: Development of VI-RADS (Vesical Imaging-Reporting And Data System). Eur Urol. 2018 Sep;74(3):294-306. doi: 10.1016/j.eururo.2018.04.029. Epub 2018 May 10. Review. — View Citation

Raghavan D. Chemotherapy and cystectomy for invasive transitional cell carcinoma of bladder. Urol Oncol. 2003 Nov-Dec;21(6):468-74. Review. — View Citation

Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, Skinner E, Bochner B, Thangathurai D, Mikhail M, Raghavan D, Skinner DG. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol. 2001 Feb 1;19(3):666-75. — View Citation

von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A, Arning M. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005 Jul 20;23(21):4602-8. — View Citation

Yin M, Joshi M, Meijer RP, Glantz M, Holder S, Harvey HA, Kaag M, Fransen van de Putte EE, Horenblas S, Drabick JJ. Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: A Systematic Review and Two-Step Meta-Analysis. Oncologist. 2016 Jun;21(6):708-15. doi: 10.1634/theoncologist.2015-0440. Epub 2016 Apr 6. Review. — View Citation

Zargar H, Espiritu PN, Fairey AS, Mertens LS, Dinney CP, Mir MC, Krabbe LM, Cookson MS, Jacobsen NE, Gandhi NM, Griffin J, Montgomery JS, Vasdev N, Yu EY, Youssef D, Xylinas E, Campain NJ, Kassouf W, Dall'Era MA, Seah JA, Ercole CE, Horenblas S, Sridhar SS, McGrath JS, Aning J, Shariat SF, Wright JL, Thorpe AC, Morgan TM, Holzbeierlein JM, Bivalacqua TJ, North S, Barocas DA, Lotan Y, Garcia JA, Stephenson AJ, Shah JB, van Rhijn BW, Daneshmand S, Spiess PE, Black PC. Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol. 2015 Feb;67(2):241-9. doi: 10.1016/j.eururo.2014.09.007. Epub 2014 Sep 23. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall survival.	Evaluate the overall survival of patients accept the modified GC neoadjuvant chemotherapy followed by radical cystectomy and lymphadenectomy.	through study completion,an average of 3 year
Primary	Changes from baseline tumor mp-MRI parameters at immediate mp-MRI evaluation.	Using the built-in tools of the MRI imaging system to assess the changes of tumor size between immediate mp-MRI evaluation and baseline mp-MRI evaluation after the use of cisplatin during the first course of modified GC neoadjuvant chemotherapy.	baseline, during the intervention (Within 24 hours after use of cisplatin of the first course of neoadjuvant chemotherapy(NAC), up to 2 weeks)
Secondary	Changes from baseline tumor mp-MRI parameters after two course of modified GC neoadjuvant chemotherapy.	Using the built-in tools of the MRI imaging system to assess the changes of tumor size conventional mp-MRI evaluation and baseline mp-MRI evaluation after the second course of modified GC neoadjuvant chemotherapy.	baseline, during the intervention(From the end date of the second course of NAC until one day before the third course of NAC, up to 7 weeks)
Secondary	Changes from baseline tumor mp-MRI parameters after three course of modified GC neoadjuvant chemotherapy.	Using the built-in tools of the MRI imaging system to assess the changes of tumor size between conventional mp-MRI evaluation and baseline mp-MRI evaluation after the third course of modified GC neoadjuvant chemotherapy.	baseline, during the intervention(From the end date of the third course of NAC until one day before surgery, up to 10 weeks)