A Feasibility Study of Durvalumab +/- Oleclumab as Neoadjuvant Therapy for Muscle-invasive Bladder Cancer (BLASST-2)

NCT03773666 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 18-507
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying a new anti-cancer drug durvalumab (MEDI4736) with or without another new anti-cancer drug Oleclumab (MEDI9447) before surgery for bladder cancer. The drugs involved in this study are:

• Durvalumab (MEDI4736)
• Oleclumab (MEDI9447)

Conditions

Muscle Invasive Bladder Cancer

Keywords

Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants Receiving at least One Dose of Study Therapy Followed by Surgery without Dose-Limiting Toxicity (DLT) up to Twelve Weeks Post-Radical Cystectomy (RC)

  2 years

Secondary Outcomes (3)

• Number of Participants Receiving at least One Cycle of Study Therapy and Undergone RC Having <pT2N0 Disease at Time of RC

  2 years

• Duration of Time of RC to Time of Documented Disease Relapse or Recurrence after RC

  2 years

• Radiographic Progression by RECIST 1.1 Criteria from Time of Baseline Screening Imaging to the End of Treatment Imaging Pre-RC

  2 years

Study Arms (2)

Durvalumab

EXPERIMENTAL

-Durvalumab will be administered intravenously every 2 weeks, with 14 consecutive days defined as a treatment cycle

Drug: Durvalumab

Durvalumab + Oleclumab

EXPERIMENTAL

* Durvalumab will be administered intravenously every 2 weeks, with 14 consecutive days defined as a treatment cycle * Oleclumab will be administered intravenously every 2 weeks, with 14 consecutive days defined as a treatment cycle

Drug: Durvalumab; Drug: Oleclumab

Interventions

Durvalumab DRUG

Durvalumab is a monoclonal antibody (an antibody is a protein produced by the body's immune system) that works by blocking the Programmed Cell Death Ligand 1 (PD-L1), a protein on cancer cells that stops the body's immune system from killing cancer cells.

Also known as: MEDI4736

Durvalumab; Durvalumab + Oleclumab

Oleclumab DRUG

Oleclumab is a monoclonal antibody that works by reducing the amount of adenosine, a small molecule called a metabolite that binds to adenosine receptors on immune cells to regulate the immune system and suppress the immune response. Reducing the amount of immunosuppressive adenosine can increase the body's immune response to kill cancer cells.

Also known as: MEDI9447

Durvalumab + Oleclumab

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 at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (See Appendix A).
• Histologically confirmed bladder transitional cell carcinoma (TCC)
• Patients with mixed histology are required to have a component of TCC, and no component of small cell histology
• T2-T4a N0 M0 disease, considered appropriate and planned for radical cystectomy
• Ineligible for cisplatin-based chemotherapy, defined by any of the following:
• Creatinine clearance (CL) \<60 mL/min. GFR should be calculated from serum/plasma creatinine using the Cockcroft-gault formula.
• CTCAE v5.0 Grade \> 1 hearing loss
• CTCAE v5.0 Grade \> 1 neuropathy
• NYHA Class \> II cardiac dysfunction
• Patients not meeting the above criteria are eligible if she/he declines perioperative cisplatin-based chemotherapy after specific informed consent describing the known benefits of cisplatin-based chemotherapy.
• Adequate organ function laboratory values as defined below:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) 1.5 x (\> 1500 per mm3)
• Platelet count ≥100 x 109/L (\>75,000 per mm3)

You may not qualify if:

• Patients with primary TCC of the ureter, urethra, or renal pelvis without TCC of the bladder
• Inoperable tumor(s) with fixation to the pelvic wall on clinical exam
• Any previous systemic chemotherapy or radiotherapy for TCC of bladder
• Participation in another clinical study with an investigational product during the last 6 months
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease (e.g. cervical cancer in situ)
• Receipt of the last dose of intravesical chemotherapy or biologic therapy
• ≤ 42 days (6 weeks) prior to the first dose of study drug for patients who have received prior intravesical chemotherapy or biologic therapy (e.g. BCG)
• Mean QT interval corrected for heart rate using Fridericia's formula (QTcF)
• ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart) for durvalumab + oleclumab cohorts only. Patient safety and the cardiac EKG should be consulted as needed.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-bycase basis after consultation with the Study Physician.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• AstraZeneca: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

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

Study Officials

• Xiao X Wei, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 8, 2018
• First Posted: December 12, 2018
• Study Start: February 20, 2019
• Primary Completion: February 4, 2021
• Study Completion: August 2, 2021
• Last Updated: September 13, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Requests may be directed to: \[contact information for Sponsor-Investigator or designee\].

Locations

US (2)