Trimodal Therapy Plus Atezolizumab in Muscle-invasive Bladder Cancer

NCT03620435 | Unknown Phase 2 DMC

• 1 other identifier: ML-39576
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm phase II trial to (1) evaluate safety and toxicity profile of intravenous Atezolizumab (anti-PDL-1) administered in combination with TMT in patients with MIBC, (2) To determine the loco-regional control rate (LCR) of TMT combined with PDL-1 blockade.

Conditions

Safety Issues

Outcome Measures

Primary Outcomes (1)

• Safety profile of intravenous Atezolizumab (anti-PDL-1) administered in combination with TMT in patients with MIBC

  Safety will be captured as (1) number of patients with Grade 3 or higher immune related Adverse Events (irAEs), (e.g. inflammatory ocular toxicities, pneumonitis, hepatitis, colitis), (2) number of patients with Grade 3 or higher treatment-related AEs (TRAE) that delay EBRT by \> 21 days. The safety assessments up to the final follow-up visits will consist of monitoring and recording adverse events, including serious adverse events and adverse events of special interest, protocol-specified safety laboratory assessments, protocol-specified vital signs, and other protocol-specified tests that are deemed critical to the safety evaluation of the study.

  2-2.5 years

Secondary Outcomes (3)

• Overall survival

  4 years

• Bladder cancer therapy impact on quality of life

  2-2.5 years

• Complete response to TMT combined with PDL-1 blockade

  2-2.5 years

Study Arms (1)

atezolizumab

EXPERIMENTAL

Atezolizumab will be given during trimodal therapy, and every 3 weeks for 16 cycles or until disease progression or unacceptable toxicity.

Drug: Atezolizumab

Interventions

Atezolizumab DRUG

Atezolizumab (1200mg iv, every 3 weeks) administered concurrently with TMT and adjuvant for up to one year

Also known as: Tecentriq

atezolizumab

Eligibility Criteria

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

You may qualify if:

• years old or older
• Histologic diagnosis of urothelial carcinoma of the bladder. Focal differentiation allowed other than small cell histology.
• Stage T2-T4a N0M0 (AJCC-TNM version 6) based on trans-urethral resection of bladder tumor (TURBT), CT imaging, +/- bimanual examination under anaesthesia (EUA).
• CT scan of chest/abdomen/pelvis within 8 weeks from the start of treatments, showing no evidence of metastatic disease.
• Attempt of complete TURBT within 56 days (8 weeks) prior to the start of chemoradiation. If TURBT was performed \> 8 weeks ago but a recent cystoscopy show no residual disease, then a repeat TURBT is not necessary.
• Life Expectancy greater than 6 months
• ECOG performance status of 2 or better
• Another primary cancer is allowed only if treated with curative intent at least 3 years prior to enrollment without evidence of recurrence or if the untreated cancer is clinical indolent (eg lower risk prostate cancer).
• Adequate hematologic reserve: Platelet count ≥ 150,000/ul, WBC ≥ 4000/ul. Anemia will be corrected to minimum hemoglobin of 100 g/L with red cell transfusions, if necessary.
• Adequate liver function with a bilirubin ≤ 1.5 ULN\[27\] and SGOT/SGPT \< 1.5 X the upper normal limit
• Patients must be considered able to tolerate systemic chemosensitizer combined with pelvic IMRT by the joint agreement of the participating radiation oncologist and medical oncologist.
• Able and willing to give written informed consent.

You may not qualify if:

• Prior systemic therapy for other urothelial tumors. Neoadjuvant chemotherapy can be considered a component of the trimodal therapy and is allowed. Superficial bladder treatments including BCG and mitomycin C are permitted if completed 6 weeks prior to therapy.
• Hypersensitive to Gemcitabine or to any ingredient in the formulation or component of the container.
• Prior RT to the pelvis
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days or five half-lives of the drug, whichever is longer, prior to enrollment
• Malignancies other than urothelial cancer within 5 years prior to Cycle 1, Day 1:
• Patients with localized lower risk prostate cancer (defined as Stage ≤T2b, Gleason score ≤ 7, and PSA at prostate cancer diagnosis ≤ 20 ng/mL\[if measured\]) treated with radical prostatectomy and without prostate-specific antigen (PSA) recurrence are eligible.
• Patients with lower risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 7 and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible.
• Patients with malignancies of a negligible risk of metastasis or death (e.g., risk of metastasis or death \<5% at 5 years) are eligible provided they meet all of the following criteria:
• Malignancy treated with expected curative intent (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated surgically with curative intent) No evidence of recurrence or metastasis by follow-up imaging and any disease-specific tumor markers
• Pre-existing medical conditions precluding treatment (e.g. previous history of immune-related adverse reactions, pneumonitis, colitis, etc.)
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
• History of autoimmune disease, 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, or glomerulonephritis. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
• Active tuberculosis
• Pregnancy or lactating mothers. Women of childbearing age must use contraception during treatment and for 5 months after the last dose of Atezolizumab. Acceptable methods are: oral contraceptives, hormonal implants, hormonal patches, IDU, Diaphragm with spermicides, cervical cape with spermicide, and condom with spermicide.

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

MUHC

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

MeSH Terms

Interventions

atezolizumab

Study Officials

• Wassim Kassouf, MD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  STUDY CHAIR

Central Study Contacts

Afsar Salimi, MSc

CONTACT

5149341934; afsar.salimi@muhc.mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: July 23, 2018
• First Posted: August 8, 2018
• Study Start: May 1, 2018
• Primary Completion: May 30, 2020
• Study Completion: December 30, 2020
• Last Updated: August 13, 2018

Record last verified: 2018-08

Locations

CA (1)