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Bladder CancerPhase 2RADIANTNCT04543110

Radiation and Durvalumab Immunotherapy As Neoadjuvant Treatment for MIBC

A Phase 2 study testing Durvalumab and Immune Modulating Radiation in people with Bladder Cancer, run by Ottawa Hospital Research Institute at 4 sites in Canada.

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 The sponsor has not verified this record for over two years, so it may be out of date.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

This study assesses the effect of sequential radiation and durvalumab immunotherapy given as treatment prior to surgery with radical cystectomy for bladder cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bladder Cancer
What is being tested?
Durvalumab and Immune Modulating Radiation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
4 sitesCanada
Study dates
29 Jan 2021to Nov 2024
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

  • Patient is willing and able to provide written informed consent
  • Patient is willing and able to comply with the protocol
  • Age ≥ 18 years
  • Body weight >30 kg.
  • Histopathologically confirmed transitional cell carcinoma/urothelial carcinoma (TCC/UC).
  • Patients with mixed transitional/non-transitional cell histologies (adenocarcinoma, squamous cell) or variant transitional histology (eg, micropapillary, plasmacytoid, sarcomatoid, nested variant, lymphoepithelioid, nested variant) are eligible.
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  • Patients with pure non-transitional cell variant histologies and/or any component of small cell histology are not eligible.
  • Clinical stage T2-T4a N0 M0 TCC/UC, as evaluated by CT, MRI and/or PET (per standard local imaging practices) within 4 weeks prior to randomization.
  • Fit and planned for cystectomy (according to local guidelines).
  • Ineligible for neoadjuvant cisplatin-based chemotherapy OR patient declines to receive neoadjuvant cisplatin-based chemotherapy
  • Ineligibility for chemotherapy include any of: i) Poor renal function (GFR < 50 ml/min) ii) Poor performance status (ECOG PS ≥ 2) iii) Significant (grade ≥2) neuropathy iv) Significant (grade ≥2) hearing loss v) Heart failure (NYHA-class-III/IV) OR b) Declining to receive neoadjuvant cisplatin regimen is documented by consultation with medical oncologist
  • Deemed by investigator to be medically fit (at the time of enrollment) for:
  • Radiotherapy to pelvis
  • Immunotherapy with durvalumab
  • Radical cystectomy
  • Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens (blocks preferred) or at least 15 unstained slides, with an associated pathology report
  • ECOG performance status of 0-1
  • Adequate hematologic and end-organ function tests.
  • Hemoglobin ≥9.0 g/dL
  • Absolute neutrophil count ≥1.5×109/L
  • Platelet count ≥100×109/L
  • Serum bilirubin ≤1.5×the upper limit of normal (ULN).
  • This will not apply to patients with confirmed Gilbert's syndrome, who will be allowed after discussion with the study sponsor / medical monitor.
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0×ULN f) CrCl >40 mL/min calculated by Cockcroft-Gault equation (using actual body weight) or measured by 24-hour urine collection for determination. In cases where both are performed, measured 24- hour urine collection will be used to determine eligibility, providing an adequate collection was performed.
  • Must have a life expectancy of at least 12 weeks at enrollment
  • Patients of childbearing / reproductive potential should use highly effective birth control methods, as defined by the investigator, during the study treatment period and for a period of at least 90 days after the last dose of durvalumab. A highly effective method of birth control (as defined in Section 8.7.2) are those that result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
  • Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test at the time of screening. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a serum follicle stimulating hormone, (FSH) level > 40 mIU/mL to confirm menopause.
  • Females must not be breastfeeding at time of enrollment until at least 90 days after last dose of durvalumab
  • Male patients should agree to not donate sperm during the study until at least 90 days after the last dose of durvalumab

Who cannot join

  • Evidence of suspected metastatic lymph node(s) (defined as short axis measurement of ≥10 mm as per IV contrast-enhanced CT or MRI scan) and/or PET-CT scan
  • Extravesical TCC/UC that invades the pelvic and/or abdominal wall for bladder cancer (T4b)
  • Distantly metastatic TCC/UC
  • Primary non-bladder (ie, ureter, urethral, or renal pelvis) TCC/UC
  • Inoperable tumor(s) with fixation to the pelvic wall on clinical exam
  • History of allogeneic organ transplantation that requires use of immunosuppressive agents. Patients with a history of allogenic stem cell transplantation are also excluded.
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  • Malignancies other than TCC/UC within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (Gleason score ≤ 3 + 4 and PSA < 10 ng/mL undergoing active surveillance and treatment naive).
  • Any history of autoimmune disease or connective tissue disorder including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, glomerulonephritis, or scleroderma.
  • The following are exceptions to this criterion: i) Patients with vitiligo or alopecia ii) Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on thyroid replacement iii) Any chronic skin condition that does not require systemic therapy iv) Patients with celiac disease controlled by diet alone may be included after consultation the study sponsor and medical monitor v) Patients without active autoimmune disease in the last 5 years may be included after consultation with the study sponsor and medical monitor
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
  • Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after discussion with the study sponsor / medical monitor.
  • History of idiopathic pulmonary fibrosis
  • History of active primary immunodeficiency
  • Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder)
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 6 months prior to enrolment, unstable arrhythmias, or unstable angina.
  • Severe infections within 4 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
  • Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the durvalumab formulation
  • History of any illness or disease that would significant compromise patient ability to receive radiation or any reason that would preclude a patient from radiation therapy as delivered by this study design
  • Prior systemic treatment for TCC/UC
  • Prior local intravesical chemotherapy or immunotherapy (e.g. BCG) is allowed if completed at least 6 weeks prior to initiation of study treatment
  • Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer- related conditions (eg, hormone replacement therapy) is acceptable.
  • Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin [BCG]), including but not limited to other anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies.
  • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
  • Note: Patients, if enrolled, should not receive live vaccine while receiving IP and up to 30 days after the last dose of IP.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • Prior pelvic radiotherapy treatment
  • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrolment
  • Concurrent enrollment in another clinical study unless it is non- interventional or during the follow-up period of an interventional study

Trial locations and contacts

4 sites in 1 country.

Michael Ong, MD contact

613-737-7700 ext. 70179

mong@toh.ca

Canada4 sites, 4 recruiting

  • Cross Cancer Institute

    Edmonton, Alberta

    Naveen Basappa

    Recruiting

  • Juravinski Cancer Centre

    Hamilton, Ontario

    Aly-Khan Lalani

    Recruiting

  • London Health Sciences Centre

    London, Ontario

    Ricardo Fernandes, MD

    Recruiting

  • The Ottawa Hospital Cancer Centre

    Ottawa, Ontario, K1H8L6

    Caroline Proulx, caproulx@ohri.ca

    Recruiting

Other trials in Canada

About this study

Official title: Neoadjuvant Immune-Modulating Radiation With Durvalumab (MEDI4736) Prior to Radical Cystectomy in Patients With Muscle-Invasive Bladder Carcinoma (RADIANT)

This study assesses the effect of sequential radiation and durvalumab immunotherapy given as treatment prior to surgery with radical cystectomy for bladder cancer.

Read the detailed description

In this phase II study, patients who are either not eligible or declined to have chemotherapy prior to surgery for muscle-invasive bladder cancer may consent and enrol to study. Patients will have single 8 Gy hypofractionated radiation to bladder followed by 3 cycles of durvalumab immunotherapy prior to radical cystectomy. This study will assess the safety and tolerability, pathological and radiological response, and immune biological correlatives to understand the effect of radiation and durvalumab.

Conditions
Bladder Cancer
Being tested
Durvalumab, Immune Modulating Radiation
Keywords
Urothelial Carcinoma, Muscle-Invasive Bladder Cancer, Neoadjuvant, Radiation, Durvalumab, Immunotherapy
Medical subject headings
Urinary Bladder Neoplasms, Carcinoma, Transitional Cell

What participants receive

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

  • DurvalumabDrug

    Also called (MEDI4736)

    Durvalumab prior to Radical Cystectomy in Patients With Muscle-Invasive Bladder Carcinoma

  • Immune Modulating RadiationRadiation

    Also called Neoadjuvant Immune Modulating Radiation

    Neoadjuvant Immune-Modulating Radiation prior to Radical Cystectomy in Patients With Muscle-Invasive Bladder Carcinoma

Study groups in NCT04543110
Study groupRoleWhat they receive
Single ArmExperimentalImmune-Modulating Radiation with Durvalumab prior to Radical Cystectomy in Patients With Muscle-Invasive Bladder Carcinoma
Receives: Drug: Durvalumab; Radiation: Immune Modulating Radiation

What is being measured

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

  1. Pathological Complete Response (pCR) Rate

    pCR rate is defined as the proportion of patients whose pathological staging was T0N0M0 as assessed using specimens obtained post radical cystectomy following the study intervention.

    Measured: Up to 2 years

Secondary outcomes (5)

  1. Adverse events

    Adverse events related to the study treatment will be identified and characterized using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. A copy of the CTCAE version 5.0 can be downloaded from the Cancer Therapy Evaluation Program website (http://ctep.cancer.gov). Data will be collected from time of confirmed study entry

    Measured: Up to 2 years

  2. Rate of delay of surgery

    Feasibility. Surgery is expected to occur within 90 days of radiotherapy. Any delay beyond that will be noted and the cause of the delay attributed to study intervention or otherwise, with supporting details.

    Measured: Up to 2 years

  3. Rate of Pathological Downstaging

    Proportion of patients who have pathological staging <T2 as determined after radical cystectomy.

    Measured: Up to 2 years

  4. Recurrence rates at 1 year and 2 years

    he proportion of patients who have radiographically confirmed recurrence of their cancer at 1 and 2 years. Time to recurrence is defined from the time of study entry to the first recurrence of disease after cystectomy. A recurrence of disease includes local (pelvic) recurrence, urinary tract recurrence, or distant metastases of urothelial carcinoma. Recurrence rate will be assessed using computed tomography (CT)/magnetic resonance imaging (MRI) and/or Positron Emission Tomography (PET)-CT (per standard local imaging practices) and pathology testing performed according to local standards and as clinically indicated.

    Measured: Up to 2 years

  5. Overall survival rate at 1 and 2 years

    The proportion of patients who are alive at 1 and 2 years. Overall survival is defined from the date of study entry until death of any cause.

    Measured: Up to 2 years

Timeline

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

  1. First posted9 Sep 2020
  2. Study start29 Jan 2021
  3. Primary completionOct 2023 (estimated)
  4. Study completionNov 2024 (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
Model description
Single-arm Phase II Fleming
Masking
None (open label)
Enrolment
16 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04543110
Sponsor's protocol ID
OTT-19-07/OZM-105
Acronym
RADIANT
Status last verified
Mar 2023
First submitted
24 Jul 2020
Last updated
23 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Qualified researchers can contact Dr. Michael Ong regarding sharing of data and be evaluated for what their purpose and plan is for the data.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab and Immune Modulating Radiation in people with Bladder Cancer, run by Ottawa Hospital Research Institute at 4 sites in Canada.

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 29 inclusion and 33 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 23 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Canada. 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?

Contact Michael Ong, MD (613-737-7700 ext. 70179, mong@toh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological Complete Response (pCR) Rate (time frame: Up to 2 years). 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 NCT04543110.

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 23 Mar 2023.

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