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

A Phase 2 Study of Check Point Inhibitor, Durvalumab (Medi4736) for Bacillus Calmette-Guérin (BCG) Refractory Urothelial Carcinoma in Situ (CIS) of the Bladder


  • Org Study ID: MCC-18788
  • Secondary ID: ESR-15-11326
  • NTC ID: NCT02901548
  • Sponsor: H. Lee Moffitt Cancer Center and Research Institute


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.

  • Overall Status
  • Start Date
    February 16, 2017
  • Phase
    Phase 2
  • Study Type


Primary Outcome 1 - Measure: Complete Response Rate at 6 Months

Primary Outcome 1 - Timeframe: 6 Months


  • Carcinoma in Situ of Bladder
  • Bladder Cancer


Inclusion Criteria:

- 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.

Exclusion Criteria:

- Muscle invasive (T2 or above) urothelial carcinoma or urothelial carcinoma outside the

- 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

- 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.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
bleeding diatheses including any participant known to have evidence of acute or
chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric
illness/social situations that would limit compliance with study requirements or
compromise the ability of the participant to give written informed consent.

- Known history of previous clinical diagnosis of tuberculosis.

- History of leptomeningeal carcinomatosis.

- Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab.

- Females who are pregnant, breast-feeding or males or females of reproductive potential
who are not employing an effective method of birth control.

- Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results.

- Uncontrolled seizures.

- Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive
of but not limited to surgery, radiation and/or corticosteroids.

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No


Name: Jingsong Zhang, M.D., Ph.D.

Role: Principal Investigator

Affiliation: H. Lee Moffitt Cancer Center and Research Institute

Overall Contact

Name: Jingsong Zhang, M.D., Ph.D.

Phone: 813-745-1363

Email: jingsong.zhang@moffitt.org


Facility Status Contact
Facility: Mount Sinai Medical Center Miami
Miami Beach, Florida 33140
United States
Status: Recruiting Contact:
Jenny Camus

Facility: H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida 33612
United States
Status: Recruiting Contact:
Natalie Burgess