Phase 2 Durvalumab (Medi4736) for Bacillus Calmette-Guérin (BCG) Refactory Urothelial Carcinoma in Situ of the Bladder

NCT02901548 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: MCC-18788ESR-15-11326
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to test if an experimental drug called Durvalumab (Medi4736) given by intravenous (IV) infusion is effective in treating carcinoma in situ (CIS) of the bladder that no longer responds to Bacillus Calmette-Guérin (BCG) and to collect information on the safety of these drugs and whether they cause any side effects.

Conditions

Carcinoma in Situ of Bladder; Bladder Cancer

Keywords

BCG refractory CIS; Urothelial CIS of bladder; Carcinoma in situ (CIS); Bacillus Calmette-Guérin (BCG); Medi4736; Durvalumab; CIS of the bladder; Bladder cancer; BCG Vaccine; Bladder diseases; Urothelial diseases

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate at 6 Months

  Complete Response Rate at month six based on the week 26 mapping biopsy in BCG refractory CIS urothelial bladder cancer. The absence of CIS of bladder on the mapping biopsies after pathological review would be considered complete response to treatment.

  6 Months

Secondary Outcomes (1)

• Complete Response Rate at 24 Months

  24 Months

Study Arms (1)

Durvalumab Plus Cystoscopy

EXPERIMENTAL

Durvalumab: Fixed dose level IV infusion every 4 weeks for 13 study treatment cycles/infusions over 12 months/1 year. Cystoscopy with biopsy will be performed every 3 months to monitor the treatment response during this one year of treatment phase. It will be performed every 6 months during year 2 of the surveillance phase.

Drug: Durvalumab; Procedure: Cystoscopy with Biopsy

Interventions

Durvalumab DRUG

Durvalumab will be given every 4 weeks at 1500 mg/kg IV for total of 12 months/13 doses.

Also known as: Medi4736

Durvalumab Plus Cystoscopy

Cystoscopy with Biopsy PROCEDURE

Cystoscopy with biopsy and transurethral resection of the bladder tumor (TURBT) (if indicated) will be performed at baseline, month 3, 6, 9, 12, 18, and 24. The month 6 and 24 cystoscopy will be done in the operating room with mapping biopsy. Rest of the cystoscopic exam with biopsy will be performed in the out-patient office setting and if clinically indicated will be repeated in the operating room. Participants will be off study if any of the biopsies document muscle invasive (T2 or above) urothelial carcinoma. Participants will also be off study if their month 6, 9, 12, 18 biopsies show persistent (month 6) or recurrent CIS or invasive (T1 or above) urothelial carcinoma. Otherwise, participants will remain on study until after the month 24 mapping biopsy.

Durvalumab Plus Cystoscopy

Eligibility Criteria

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

You may qualify if:

• Must have pathologically confirmed urothelial carcinoma in situ (CIS) of the bladder that meet one of the following criteria: 1. Persistence of high-grade CIS at 6 months following an adequate course of BCG; OR - 2. Stage/grade progression at 3 months after induction BCG; OR - 3. Recurrence of high-grade CIS after achieving a disease-free state (i.e., CR) following induction of an adequate course of BCG that occurs \< 9 months after the last exposure to BCG; OR - 4. Persistent CIS noted on the bladder biopsies within 3 months of completing at least 2 induction BCG (minimum of five weekly instillations). An adequate course of BCG should be defined as at least one course of induction (minimum of five weekly instillations) and one maintenance (two of three instillations) in a 6 months period, with an exception for any patient with grade/stage progression after induction BCG (minimum of five weekly instillations).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Adequate organ and marrow function.
• Written informed consent and any locally required authorization (e.g., HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations.
• Females must not be pregnant, or breast feeding and must have a negative urine or serum pregnancy test within 28 days prior to treatment on day 1. Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception from the time of screening, and must agree to continue using such precautions for 90 days after the final dose of Durvalumab. They must also refrain from egg cell donation for 90 days after the final dose of Durvalumab.
• Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception and refrain from sperm donation from Day 1 through 90 days after receipt of the final dose of Durvalumab.

You may not qualify if:

• Muscle invasive (T2 or above) urothelial carcinoma or urothelial carcinoma outside the bladder.
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) or previous enrolment in the present 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 anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, tyrosine kinase inhibitor, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 30 days prior to the first dose of study drug and within 6 weeks for nitrosourea, mitomycin C or intravesical therapy).
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
• Any unresolved toxicity (CTCAE grade 2 or above) from previous anti-cancer therapy. \[Potential participants with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy)\].
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1.
• Active or prior documented autoimmune disease within the past 2 years. NOTE: Potential participants with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• History of primary immunodeficiency.
• History of allogeneic organ transplant.
• History of pneumonitis.
• History of hypersensitivity to durvalumab or any excipient.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• AstraZeneca: collaborator

Study Sites (2)

Mount Sinai Medical Center Miami

Miami Beach, Florida, 33140, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma in Situ; Urinary Bladder Diseases

Interventions

durvalumab; Cystoscopy; Biopsy

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Endoscopy; Diagnostic Techniques, Surgical; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Urological; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Specimen Handling; Investigative Techniques

Limitations and Caveats

All reported deaths were on post study treatment survival follow up.

Results Point of Contact

• Title: Jingsong Zhang, MD, PhD
• Organization: Moffitt Cancer Center

Jingsong.Zhang@moffitt.org

813-745-6926

Study Officials

• Jingsong Zhang, M.D., Ph.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: September 12, 2016
• First Posted: September 15, 2016
• Study Start: February 16, 2017
• Primary Completion: July 24, 2020
• Study Completion: September 7, 2021
• Last Updated: July 29, 2022
• Results First Posted: June 11, 2021

Record last verified: 2022-07

Locations

US (2)