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Urinary Bladder CancerPhase 2RACE ITNCT03529890

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

A Phase 2 study testing Nivolumab, Radiation therapy of the pelvis and Radical cystectomy with standardized pelvic lymphadenectomy in people with Urinary Bladder Cancer, run by Technical University of Munich at 3 sites in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urinary Bladder Cancer
What is being tested?
Nivolumab, Radiation therapy of the pelvis and Radical cystectomy with standardized pelvic lymphadenectomy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
3 sitesGermany
Study dates
4 Feb 2019to Aug 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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):
  • cT3/4 in imaging studies (bladder wall thickening or infiltration of perivesical fat/adjacent organs)
  • Presence of hydronephrosis (or status post nephrostomy/ureteral stent due to hydronephrosis)
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  • 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
  • Estimated life expectancy > 6 months
  • Adequate function of bone marrow, liver and kidney:
  • WBC ≥ 2000/μL
  • Neutrophils ≥ 1500/μL
  • Platelets ≥ 100 × 103/μL
  • Hemoglobin ≥ 9.0 g/dL
  • AST ≤ 3 × ULN
  • ALT ≤ 3 × ULN
  • Total bilirubin ≤ 1.5 × ULN (except in participants with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • GFR ≥ 15 mL/min without hydronephrosis. In case of hydronephrosis, drainage should be performed prior to inclusion preferably by nephrostomy, alternatively by ureteral stent placement. Use measured creatinine-clearance or estimated clearance (Cockcroft-Gault formula):
  • Female CrCl = [(140 - age in years) × weight in kg × 0.85] / [72 x serum creatinine in mg/dL] ii. Male CrCl = [(140 - age in years) × weight in kg × 1.00] / [72 x serum creatinine in mg/dL]
  • Informed consent:
  • Participants must have signed and dated an IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care.
  • Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study
  • Body weight 35 kg - 160 kg
  • Female patients with childbearing potential must have a negative serum pregnancy test prior to start of trial.
  • Women of childbearing potential (WOCBP) and men (who are sexually active with WOCBP) must use any contraceptive method with a failure rate of less than 1% per year (see Appendix 15.7). These patients will be instructed to adhere to contraception for the period between inclusion into the study and surgery (which leads to sterility). Women who are not of childbearing potential (i.e. who are postmenopausal or surgically sterile) as well as sterile men do not require contraception. If patients do not undergo surgery or in the rare case of fertility preserving cystectomy , effective contraception should be used for at least 5 months following the last dose of Nivolumab. In the latter instance serum pregnancy testing is required in WOCBP at the end of the 5 months.

Who cannot join

  • Metastatic disease defined as distant metastasis or suspicious lymph nodes (> 10mm short axis) outside the pelvis (clearly above aortic bifurcation) using RECIST 1.1 criteria. Enlarged lymph nodes in the pelvis below or at aortic bifurcation are NO exclusion criterion irrespective of size.
  • 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)
  • Experimental therapy or clinical trial at time of inclusion or the previous 4 weeks
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  • 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)
  • Any uncontrolled or severe cardiovascular or pulmonary disease determined by the investigator, including i) NYHA functional classification III or IV, congestive heart failure, unstable or poorly controlled angina, uncontrolled hypertension, serious arrhythmia or myocardial infarction in previous 12 months before inclusion; ii) Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxic.
  • End-stage kidney disease defined as GFR < 15ml/min or need for dialysis in absence of hydronephrosis. In case of hydronephrosis, drainage should be performed prior to inclusion preferably by nephrostomy, alternatively by ureteral stent placement.
  • 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.].
  • Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is longer.
  • Hypersensitivity to Nivolumab or any of it's excipients.
  • Prior organ transplantation
  • Positive test result for hepatitis B or C indicating acute or chronic infection.
  • Positiv HIV test or acquired immunodeficiency syndrome (AIDS)
  • Serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the patient to receive protocol therapy
  • Gastrointestinal disorders, particularly those with high risk of perforation or fistula formation including i) active peptic ulcer disease or active inflammatory bowel disease (incl. ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis during screening and/or ii) history of abdominal fistula or bowel perforation within 6 months prior to first dose of study treatment.

Trial locations and contacts

3 sites in 1 country.

Germany3 sites

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

    München

  • Universitätsklinikum Ulm; Klinik für Urologie

    Ulm

  • Department of Urology, Universitätsklinikum Würzburg

    Würzburg

Other trials in Germany

About this study

Official title: 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

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

Read the detailed description

Patients with locally advanced bladder cancer have a poor prognosis despite radical surgical therapy. The addition of perioperative combination chemotherapy did not add significant benefit to surgery alone. There is data indicating a synergistic effect of radiation and immunotherapy. Therefore, combined application of radiotherapy with Nivolumab before radical cystectomy might lead to improved cure rates and local control in this poor prognosis group with locally advanced bladder cancer. The aim of this phase-II study is to assess feasibility and safety of immunotherapy combined with neoadjuvant radiation before radical cystectomy.

Being tested
Nivolumab, Radiation therapy of the pelvis, Radical cystectomy with standardized pelvic lymphadenectomy
Keywords
locally advanced urothelial carcinoma, immunotherapy, cystectomy, radiation, nivolumab
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called Opdivo

    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

  • Radiation therapy of the pelvisRadiation

    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)

  • Radical cystectomy with standardized pelvic lymphadenectomyProcedure or surgery

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

Study groups in NCT03529890
Study groupRoleWhat they receive
Radio-Immunotherapy before cystectomyExperimentalSingle arm treatment with Nivolumab during a neoadjuvant radiation therapy of the pelvis before radical cystectomy with standardized pelvic lymphadenectomy
Receives: Drug: Nivolumab; Radiation: Radiation therapy of the pelvis; Procedure: Radical cystectomy with standardized pelvic lymphadenectomy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: end of week 15

Secondary outcomes (8)

  1. Acute toxicity of preoperative radio-immunotherapy

    according to CTCAE v4, typical predefined side effects of surgery will be excluded from analysis

    Measured: beginning of treatment until 3 months after end of therapy

  2. Rate of immune related toxicities

    immune mediated pneumonitis, colitis, Hepatitis, hypophysitis, adrenal insufficiency, hypo-/hyperthyroidism, Diabetes (type 1), Nephritis, Skin reactions

    Measured: beginning of treatment until 12 months after cystectomy

  3. Late toxicity

    according to CTCAE v4

    Measured: 3 months after end of therapy until 12 months after cystectomy

  4. Disease free survival

    defined by local recurrence or distant metastasis dor death in R0 resected patients during 1 year follow

    Measured: until 12 months after cystectomy

  5. Overall survival

    time to death by any cause

    Measured: until 12 months after cystectomy

  6. radiological Overall Response rate

    complete Remission, partial Remission, stable disease, progressive disease

    Measured: after completion of radioimmunotherapy before cystectomy (week 12; range 11-14)

  7. ypT0 rate

    rate of pT0 after therapy

    Measured: after cystectomy was performed (week 16)

  8. surgical margin Status

    R0, R1, R2

    Measured: after cystectomy was performed (week 16)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2018
  2. Study start4 Feb 2019
  3. Primary completion14 Apr 2022
  4. Study completionAug 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03529890
Sponsor's protocol ID
AB 65/18
Other IDs
CA209-9WT
Acronym
RACE IT
Status last verified
Dec 2021
First submitted
26 Mar 2018
Last updated
20 Oct 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 31900121

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, Radiation therapy of the pelvis and Radical cystectomy with standardized pelvic lymphadenectomy in people with Urinary Bladder Cancer, run by Technical University of Munich at 3 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 20 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of patients with completed Treatment (time frame: end of week 15). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03529890, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2022.

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