Radiation and Durvalumab Immunotherapy As Neoadjuvant Treatment for MIBC

NCT04543110 | Unknown Phase 2 DMC

• 1 other identifier: OTT-19-07/OZM-105
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Bladder Cancer

Keywords

Urothelial Carcinoma; Muscle-Invasive Bladder Cancer; Neoadjuvant; Radiation; Durvalumab; Immunotherapy

Outcome Measures

Primary Outcomes (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.

  Up to 2 years

Secondary Outcomes (5)

• Adverse events

  Up to 2 years

• Rate of delay of surgery

  Up to 2 years

• Rate of Pathological Downstaging

  Up to 2 years

• Recurrence rates at 1 year and 2 years

  Up to 2 years

• Overall survival rate at 1 and 2 years

  Up to 2 years

Study Arms (1)

Single Arm

EXPERIMENTAL

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

Drug: Durvalumab; Radiation: Immune Modulating Radiation

Interventions

Durvalumab DRUG

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

Also known as: (MEDI4736)

Single Arm

Immune Modulating Radiation RADIATION

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

Also known as: Neoadjuvant Immune Modulating Radiation

Single Arm

Eligibility Criteria

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

You may qualify if:

• 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.
• 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
• a) 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

You may not qualify if:

• 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.
• 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.
• a) 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).
• a) 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.

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Cross Cancer Institute: collaborator
• Hamilton Health Sciences Corporation: collaborator
• London Health Sciences Centre: collaborator
• Ontario Institute for Cancer Research: collaborator
• AstraZeneca: collaborator
• Ozmosis Research Inc.: collaborator

Study Sites (4)

Cross Cancer Institute

Edmonton, Alberta, Canada

RECRUITING

Juravinski Cancer Centre

Hamilton, Ontario, Canada

RECRUITING

London Health Sciences Centre

London, Ontario, Canada

RECRUITING

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H8L6, Canada

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

durvalumab

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; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Michael Ong, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

• Naveen Basappa, MD

  Cross Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael Ong, MD

CONTACT

613-737-7700; mong@toh.ca

Study Design

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

Model Details: Single-arm Phase II Fleming

Study Record Dates

• First Submitted: July 24, 2020
• First Posted: September 9, 2020
• Study Start: January 29, 2021
• Primary Completion: October 1, 2023
• Study Completion: November 1, 2024
• Last Updated: March 23, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)