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BRIEF TITLE: Trial of Anti-PD-1 (Nivolumab) in Bladder Cancer Patients Recently Treated With Intravesical BCG Immunotherapy

A Pilot Trial of Anti-PD-1 (Nivolumab) in Bladder Cancer Patients Recently Treated With Intravesical BCG Immunotherapy

  • Org Study ID: 2016-0432
  • Secondary ID: NCI-2017-00647
  • NCT ID: NCT03106610
  • NCT Alias:
  • Sponsor: M.D. Anderson Cancer Center - Other
  • Source: M.D. Anderson Cancer Center

Brief Summary

The goal of this clinical research study is to learn about the tolerability of nivolumab in patients who have bladder cancer, were previously treated with BCG immunotherapy, and who have a cystectomy (removal of all or part of the bladder) scheduled as part of their standard care. This is an investigational study. Nivolumab is FDA approved and commercially available to treat metastatic (has spread) melanoma or non-small cell lung cancer (NSCLC) after the disease has gotten worse while receiving platinum-based chemotherapy. The use of nivolumab in this study is considered investigational. Up to 10 participants will take part in this study. All will be enrolled at MD Anderson.

Detailed Description

Study Drug Administration:

Each study cycle is 14 days (2 weeks).

If you are found to be eligible to take part in this study, you will receive nivolumab by
vein over about 60 minutes on Day 1 of Cycles 1-3.

Length of Study:

You may receive nivolumab for up to 3 cycles before your scheduled surgery. You will no
longer be able to take the study drug if the disease gets worse, if intolerable side effects
occur, or if you are unable to follow study directions.

Your participation on the study will be over after the follow-up visits (described below).

Study Visits

On Day 1 of Cycles 1-3 and at the visit before your surgery:

- You will have a physical exam.

- Blood (about 3-4 teaspoons) will be drawn for routine tests.

- You will be asked to complete 2 quality-of-life questionnaires. These will take about 10
minutes to complete.

- If you can become pregnant, urine or part of the above routine blood sample will be used
for a pregnancy test.

Surgery (Cystectomy):

About 8 weeks after you join the study, you will have surgery for bladder cancer. You will
sign a separate consent form that describes the surgery and its risks.

Follow Up:

About 4 weeks after surgery:

- You will have a physical exam.

- Blood (about 3-4 teaspoons) will be drawn for routine tests.

- You will be asked to complete the 2 quality-of-life questionnaires.

Overal Status Start Date Phase Study Type
Recruiting July 7, 2017 Phase 1 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Safety of Nivolumab in Subjects Previously Treated with Intravesical Bacillus Calmette-Guerin (BCG) Immunotherapy assessed per NCI CTCAE version 4

Primary Outcome 1 - Time Frame: 12 weeks


  • Bladder Cancer


Inclusion Criteria:

1. Patients included in the study must be >/= 18 years old.

2. Histological or cytological evidence of transitional cell carcinoma or carcinoma in
situ of the urothelium involving the bladder or prostatic urethra following treatment
with BCG with the recommendation to proceed for cystectomy. Minor histologic variants
(< 50% overall) are acceptable. Diagnosis must be within 1 year of study entry.

3. Patent must have BCG unresponsive non-muscle-invasive bladder cancer defined as:
Persistent or recurrence of CIS within 12 months, or recurrence of CIS with Ta/T1
papillary disease within 12 months, or recurrence of high grade Ta or T1 papillary
disease alone within 6 months of receiving at least two courses of intravesical BCG
(at least five of six induction doses and at least two doses of either a maintenance
course of BCG or a 2nd re-induction of BCG; or T1 high-grade disease at the first
evaluation following induction of BCG alone (at least five of six induction doses).

4. Subjects must have received intravesical treatment with at least two doses of BCG
within six months of nivolumab treatment initiation.

5. Evaluable tumor tissue (archived or new biopsy) must be available for pre-treatment
biomarker analysis and baseline immune monitoring studies

6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.

7. Screening laboratory values must meet the following criteria and must be obtained
within 14 days prior to first dose: a) WBC >/= 2000/µL; b) Neutrophils >/= 1500/µL; c)
Platelets >/= 100 x 10^3/mcl; d) Hemoglobin >/= 9.0 g/dL; e) AST and ALT f) Total Bilirubin total bilirubin < 3.0 mg/dL)

8. Inclusion 6) continued; g.Serum creatinine >/=30 mL/min (using the Cockcroft-Gault formula): 1) Female CrCl = (140 - age in
years) x weight in kg x 0.85 / 72 x serum creatinine in mg/dL; 2) Male CrCl = (140 -
age in years) x weight in kg x 1.00 / 72 x serum creatinine in mg/dL

9. Ability to understand and willingness to sign a written informed consent document.

10. Females of childbearing potential who are sexually active with a non-sterilized male
partner and non-sterilized males must use a highly effective method of contraception
for 28 days prior to the first dose of investigational product, and must agree to
continue using such precautions for 180 days after the final dose of investigational
product; cessation of contraception after this point should be discussed with a
responsible physician. Periodic abstinence, the rhythm method, and the withdrawal
method are not acceptable methods of contraception. They must also refrain from egg
cell donation for 180 days after the final dose of investigational product;

11. Inclusion 9) continued; a) Females of childbearing potential are defined as those who
are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or
complete hysterectomy) or postmenopausal (defined as 12 months with no menses without
an alternative medical cause)

12. Inclusion 9) continued; b) A highly effective method of contraception is defined as
one that results in a low failure rate (ie, less than 1% per year) when used
consistently and correctly. The acceptable methods of contraception are: Barrier
Method (e.g. male condom with spermicide, copper T intrauterine device, or
levonorgestrel-releasing intrauterine system - Mirena®) or Hormonal Methods (e.g.
implants, hormone shot or injection, combined pill, minipill, or patch).

Exclusion Criteria:

1. Patients with high risk muscle invasive urothelial carcinoma (hydronephrosis, palpable
mass on examination under anesthesia,muscle invasive urothelial carcinoma with
lymphovascular invasion on pathologic specimen, >T3 disease) or those with lymph node
positive or metastatic disease are to be excluded.

2. Any serious or uncontrolled medical disorder that, in the opinion of the investigator,
may increase the risk associated with study participation or study drug
administration, impair the ability of the subject to receive protocol therapy, or
interfere with the interpretation of study results.

3. Prior malignancy active within the previous 3 years except for locally curable cancers
that have been apparently cured, such as basal or squamous cell skin cancer, prostate
cancer without evidence of PSA progression or carcinoma in situ such as the following:
gastric, prostate, cervix, colon, melanoma, or breast for example.

4. Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo,
type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only
requiring hormone replacement, psoriasis not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger are permitted
to enroll.

5. Subjects with a condition requiring systemic treatment with either corticosteroids (>
10 mg daily prednisone equivalents) or other immunosuppressive medications within 14
days of study drug administration. Inhaled or topical steroids and adrenal replacement
doses > 10 mg daily prednisone equivalents are permitted in the absence of active
autoimmune disease.

6. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-cytotoxic
T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody, anti-CD137, or any other
antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint

7. All toxicities attributed to prior anti-cancer therapy other than neuropathy, alopecia
and fatigue must have resolved to Grade 1 (NCI CTCAE version 4) or baseline before
administration of study drug. Subjects with toxicities attributed to prior anti-cancer
therapy which are not expected to resolve and result in long lasting sequelae, such as
neuropathy after platinum based therapy, are permitted to enroll. Neuropathy must have
resolved to Grade 2 (NCI CTCAE version 4).

8. Treatment with any chemotherapy, radiation therapy, biologics for cancer, or
investigational therapy within 28 days of first administration of study treatment.

9. Physical and Laboratory Test Findings; a) Positive test for hepatitis B virus surface
antigen (HBV sAg) or hepatitis C virus ribonucleic acid (RNA) or hepatitis C antibody
(HCV antibody) indicating acute or chronic infection; b) Known history of testing
positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency
syndrome (AIDS).

10. Allergies and Adverse Drug Reaction; a) History of allergy to study drug components;
b) History of severe hypersensitivity reaction to any monoclonal antibody.

11. Sex and Reproductive Status; a) Women of childbearing potential (WOCBP) who are
pregnant or breastfeeding; b) Women with a positive pregnancy test at enrollment or
prior to administration of study medication

12. Prisoners or subjects who are involuntarily incarcerated

13. Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness.
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Matthew Campbell, MD

Role: Principal Investigator

Affiliation: M.D. Anderson Cancer Center

Overall Contact

Name: Matthew Campbell, MD

Phone: 713-792-2830


Link: University of Texas MD Anderson Cancer Center Website


Facility Status Contact
University of Texas MD Anderson Cancer Center
Houston, Texas 77030
United States
Recruiting Clinical Research Operations