Radio-Immunotherapy Before Cystectomy in Locally Advanced Urothelial Carcinoma of the Bladder

NCT03529890 | Unknown Phase 2 DMC

• 2 other identifiers: AB 65/18CA209-9WT
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 3

Brief Summary

A prospective, single arm, multicenter, Phase II-Trial to assess safety and efficacy of preoperative Radiation therapy before radical CystEctomy combined with ImmunoTherapy in locally advanced urothelial carcinoma of the bladder

Conditions

Urinary Bladder Cancer

Keywords

locally advanced urothelial carcinoma; immunotherapy; cystectomy; radiation; nivolumab

Outcome Measures

Primary Outcomes (1)

• Rate of patients with completed Treatment

  Completed Treatment (consisting of radio-immunotherapy and radical cystectomy) is defined by Administration of at least 2 complete cycles of nivolumab 240 mg and Administration of at least 23 of planned 28 Radiation fractions (at least 41.4 Gy in total)

  end of week 15

Secondary Outcomes (8)

• Acute toxicity of preoperative radio-immunotherapy

  beginning of treatment until 3 months after end of therapy

• Rate of immune related toxicities

  beginning of treatment until 12 months after cystectomy

• Late toxicity

  3 months after end of therapy until 12 months after cystectomy

• Disease free survival

  until 12 months after cystectomy

• Overall survival

  until 12 months after cystectomy

Study Arms (1)

Radio-Immunotherapy before cystectomy

EXPERIMENTAL

Single arm treatment with Nivolumab during a neoadjuvant radiation therapy of the pelvis before radical cystectomy with standardized pelvic lymphadenectomy

Drug: Nivolumab; Radiation: Radiation therapy of the pelvis; Procedure: Radical cystectomy with standardized pelvic lymphadenectomy

Interventions

Nivolumab DRUG

Experimental intervention: Immunotherapy with 4 cycles of Nivolumab: 240 mg intravenously every 2 weeks, starting one week before radiotherapy (week1, d1), last infusion on week 7, d1

Also known as: Opdivo

Radio-Immunotherapy before cystectomy

Radiation therapy of the pelvis RADIATION

Neoadjuvant radiation therapy of pelvis with 45+5,4 Gy for 6 weeks: 28 x 1.8 Gy including a boost of bladder with 5.4 Gy, starting with week 2 (d1)

Radio-Immunotherapy before cystectomy

Radical cystectomy with standardized pelvic lymphadenectomy PROCEDURE

Radical cystectomy with standardized bilateral pelvic lymphadenectomy: performed between week 11 - 15 (Aim: week 13)

Radio-Immunotherapy before cystectomy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed, locally advanced bladder cancer (cT3/4 cN0/N+ cM0)
• Urothelial cancer with at least 10% urothelial differentiation (excluding presence of small cell differentiation, which is not allowed in any percentage)
• Histologic proof of muscle invasion in TUR-B specimen: ≥ pT2
• Signs of locally advanced bladder cancer (at least one of the following must apply):
• i. cT3/4 in imaging studies (bladder wall thickening or infiltration of perivesical fat/adjacent organs)
• ii. Presence of hydronephrosis (or status post nephrostomy/ureteral stent due to hydronephrosis)
• iii. Pelvic lymph nodes ≥ 8 mm in short axis
• Ineligibility for neoadjuvant cisplatin-based chemotherapy due to any of the following criteria:
• Creatinine Clearance (using the Cockcroft-Gault formula) \< 60 mL/min
• Hearing loss ≥ grade 2 (CTCAE version 4)
• Peripheral neuropathy ≥ grade 2 (CTCAE version 4)
• ECOG performance score 2
• Subjects that are eligible for cisplatin may be candidates if they refuse available neoadjuvant cisplatin-based chemotherapy, despite being informed by the investigator about the treatment options. The subject's refusal must be thoroughly documented.
• Eligible for radical cystectomy
• ECOG 0 - 2

You may not qualify if:

• Prior chemotherapy before treatment (not including intravesical chemotherapy)
• Prior radiation therapy of the pelvis
• Active, known or suspected autoimmune disease (not including: vitiligo, allergic rhinitis/asthma, type 1 diabetes mellitus, residual hypothyroidism due to an autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger)
• Immunosuppressive treatment with corticosteroids or other drugs within 14 days of study drug administration (not including: inhaled or topical steroids and adrenal replacement doses are permitted in the absence of active autoimmune disease)
• Previous treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways (not including BCG therapy)
• Thromboembolic events like pulmonary embolism or apoplexy in previous 3 months
• Other active tumor disease (not including basal cell carcinoma of the skin, carcinoma in situ of the cervix and incidental prostate carcinoma). Tumor is regarded non active after curative therapy and 5 years of follow up without pathological findings.
• Medium to extended surgery or trauma in the previous 4 weeks (not including transurethral bladder resection, nephrostomy or ureteral stent or biopsy)
• Uncontrolled and serious somatic or mental illness
• Age \< 18 years
• Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
• Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities \[§ 40 Abs. 1 S. 3 Nr. 4 AMG\].
• Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts \[§ 40 Abs. 1 S. 3 Nr. 3a AMG\].
• Female subjects who are pregnant, breast-feeding or male/female patients of childbearing potential who are not employing an effective method of birth control (failure rate of less than 1% per year). \[Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessaries (only hormonal devices), sexual abstinence or vasectomy of the partner, see Appendix 15.7.\].
• Hypersensitivity to Nivolumab or any of it's excipients.

Sponsors & Collaborators

• Technical University of Munich: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Department of Urology, Klinikum rechts der Isar der Technischen Universität München

München, Germany

Location

Universitätsklinikum Ulm; Klinik für Urologie

Ulm, Germany

Location

Department of Urology, Universitätsklinikum Würzburg

Würzburg, Germany

Location

Related Publications (1)

• Schmid SC, Koll FJ, Rodel C, Maisch P, Sauter A, Beckert F, Seitz A, Kubler H, Flentje M, Chun F, Combs SE, Schiller K, Gschwend JE, Retz M. Radiation therapy before radical cystectomy combined with immunotherapy in locally advanced bladder cancer - study protocol of a prospective, single arm, multicenter phase II trial (RACE IT). BMC Cancer. 2020 Jan 3;20(1):8. doi: 10.1186/s12885-019-6503-6.

  PMID: 31900121 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Nivolumab; Cystectomy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Sebastian C Schmid, PD Dr. med

  Department of Urology, Klinikum rechts der Isar der Technischen Universität München

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2018
• First Posted: May 18, 2018
• Study Start: February 4, 2019
• Primary Completion: April 14, 2022
• Study Completion: August 1, 2023
• Last Updated: October 20, 2022

Record last verified: 2021-12

Locations

DE (3)