An Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Multi-Centre, Multi-Arm Phase 1b Study in Patients with Muscle Invasive Bladder Cancer (MIBC) who have progressed on prior treatment (BISCAY)

Protocol: 
AAAQ4008
Phase: 
I

An Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Multi-Centre, Multi-Arm Phase 1b Study in Patients with Muscle Invasive Bladder Cancer (MIBC) who have progressed on prior treatment (BISCAY)

This research study is designed to determine whether the study drugs are effective in treating muscle invasive bladder cancer in patients whose cancer did not stop, or whose cancer returned after being treated with other drugs, and study what kind of side effects are caused by these study drugs. To do this, a group of patients will be given MEDI4736 in combination with AZD4547, and compared with another group who will receive AZD4547 alone. You have been asked to take part in this research study because your bladder cancer is advanced, and treatment with 2 new investigational drugs (MEDI4736 and AZD4547) is being tested. The study drugs are “investigational drugs” because they are not approved by the Food and Drug Administration (FDA) to treat muscle invasive bladder cancer. When AZD4547 works, it causes your cancer cells to die and keeps the cells from spreading to other parts of your body. MEDI4736 works by helping the body’s own immune system recognize and start to attack the cancer cells. It is thought that when combined, MEDI4736 will make AZD4547 more effective at killing cancer cells. This study will consist of 2 groups of patients: 1 group treated with the MEDI4736 plus AZD4547 and 1 group treated with AZD4547 alone. The purpose of this study is to answer the following questions: 1. What is the best dose of the study drug that can be given to patients with muscle invasive bladder cancer when AZD4547 is given at the same time? 2. What are the side effects of AZD4547 given alone and in combination with MEDI4736? 3. What early effect, if any, is AZD4547 alone or combined with MEDI4736 having on your cancer? 4. How much of the study drugs are in the blood at specific times after dosing? You will be in this study for about 12 months but possibly longer or shorter depending on how your tumor responds to the treatment. Approximately 50 people will take part in this part of the study.

Are you Eligible? (Inclusion Criteria)

Inclusion:
1) Histological confirmation of metastatic muscle invasive bladder cancer
2) Patients may be second- or third-line patients. Patients must have received
1 accepted first-line treatment (eg, methotrexate, vinblastine, doxorubicin, and
cisplatin/gemcitabine). All patients must have documented radiological
progression on the last treatment administered prior to enrolling in the study.
3) Any patient who has failed adjuvant or neo-adjuvant chemotherapy within a year
of Screening

Exclusion:
Prior exposure to any of the following:
- Any other immunotherapy (eg, a CTLA4, PD-1 or PD-L1 inhibitor) before the
first dose of study treatment
- Any other chemotherapy or anticancer agents within 4 weeks before the
first dose of study treatment
- Radiotherapy of the primary site with a wide field of radiation within 4 weeks
or radiotherapy with a limited field of radiation for palliation within 2 weeks
before the first dose of study treatment
- Any investigational agents or study drugs from a previous clinical study within
30 days before the first dose of study treatment.

Specialty Area(s)

Immunotherapy

Trial Location

Herbert Irving Comprehensive Cancer Center
161 Fort Washington Ave.
Herbert Irving Pavilion
New York, NY 10032
United States