Neoadjuvant Immunotherapy With Durvalumab and Tremelimumab for Bladder Cancer Patients Ineligible for Cisplatin

NCT03234153 | Terminated Phase 2

• 1 other identifier: NITIMIB-Trial
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The trial assess the safety and antitumor activity of the anti-PD-L1 antibody Durvalumab in combination with the anti-CTLA4 antibody Tremelimumab.

Conditions

Muscle-invasive Bladder Cancer

Keywords

Muscle-invasive Bladder Cancer; Ineligible for Cisplatin-based Chemotherapy; Durvalumab; Tremelimumab

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Response rate (computer tomography or magnet resonance imaging) as measured per standard RECIST v1.1 after four cycles of combined treatment with Durvalumab (MEDI4736) and tremelimumab.

  16 weeks

Secondary Outcomes (3)

• Adverse Events

  26 weeks

• Recurrence-free Survival

  78 weeks

• Overall Survival

  78 weeks

Study Arms (1)

Durvalumab and Tremelimumab

EXPERIMENTAL

Durvalumab 1500 mg i.v. every 4 weeks in combination with Tremelimumab 75 mg i.v. every 4 weeks for a total of 4 cycles before surgery.

Drug: Durvalumab (Imfinzi); Drug: Tremelimumab

Interventions

Durvalumab (Imfinzi) DRUG

Durvalumab 1500 mg i.v. every 4 weeks in combination with Tremelimumab 75 mg i.v. every 4 weeks for a total of 4 cycles before surgery.

Also known as: Neoadjuvant Immunotherapy

Durvalumab and Tremelimumab

Tremelimumab DRUG

Tremelimumab 75 mg i.v. in combination with Durvalumab 1500 mg i.v. every 4 weeks every 4 weeks for a total of 4 cycles before surgery.

Also known as: Neoadjuvant Immunotherapy

Durvalumab and Tremelimumab

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Signed Informed Consent Form
• ECOG performance status of 0 or 1
• Histologically confirmed muscle-invasive urothelial carcinoma of the bladder (T2-T4 and/or N+). Patients with mixed histologies are required to have a dominant transitional cell pattern.
• Measurable disease according to RECIST v1.1 criteria
• Representative fresh tumor specimen; TURB (transurethral resection of bladder ) specimens must contain a muscle invasive component (at least T2)
• Ineligible to receive cisplatin-based neoadjuvant chemotherapy based on at least one of the following criteria:
• Creatinin clearance less than 60ml/min (24h urine)
• CTCAE Gr ≥ 2 hearing loss
• CTCAE Gr ≥ 2 neuropathy
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
• Body weight \>30 kg
• Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 14 days prior the first study treatment:
• Absolute neutrophil count (ANC) ≥ 1500 cells/µl
• WBC counts \> 2500/µl

You may not qualify if:

• Known metastatic disease
• Intravesical chemo- or biological/immune (BCG) therapy within 6 weeks of first treatment dose
• Prio treatment with immune checkpoint blockade therapies like anti-CTLA-4, anti-PD1 and anti-PD-L1 therapeutic antibodies, including durvalumab and tremelimumab
• 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 anti-phospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis or glomerulonephritis Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study. Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen are eligible for this study
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational drug.
• Female patients who are pregnant or breast feeding as well as male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy.
• Known allergy or hypersensitivity to any of the investigational study drugs or any of the study excipients.
• Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
• Uncontrolled intercurrent illness, including but limited to, ongoing infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina.
• Patients with prior allogeneic stem cell or solid organ transplantation
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan
• Positive test for HIV
• Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen test at screening) or hepatitis C.
• Active tuberculosis

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• AstraZeneca: collaborator

Study Sites (1)

Departement of Medical Oncology, University Hospital Berne

Bern, 3010, Switzerland

Location

MeSH Terms

Interventions

durvalumab; tremelimumab

Study Officials

• Julian Schardt, MD

  Departement of Medical Oncology, University Hospital Berne

  STUDY CHAIR

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 open-Label prospective Phase II

Study Record Dates

• First Submitted: July 26, 2017
• First Posted: July 31, 2017
• Study Start: July 15, 2018
• Primary Completion: November 8, 2019
• Study Completion: May 18, 2020
• Last Updated: June 17, 2020

Record last verified: 2020-06

Locations

CH (1)