Clinical trial NCT01094496: A Study of the CDX-1307 Vaccine Regimen in Patients With Newly Diagnosed Muscle-Invasive Bladder Cancer (The "N-ABLE" Study)
Official title: A Phase II, Open-Label Study of the CDX-1307 Vaccine Regimen as Neoadjuvant and Adjuvant Therapy in Patients With Newly Diagnosed Muscle-Invasive Bladder Cancer Expressing hCG-β
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Bladder Cancer
Keywords: bladder cancer
immunotherapy
cystectomy
cancer vaccine
human chorionic gonadotropin
hCG
urogenital neoplasms
urinary bladder neoplasms
muscle invasive
non-metastatic
transitional cell (urothelial) bladder cancer
Lead sponsor: Celldex Therapeutics
Sponsor class: INDUSTRY
First posted: 2010-03-29
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The major purpose of this study is to examine the anti-tumor activity of the CDX-1307 vaccine regimen when it is given before and after bladder cancer surgery. The study will also provide information about the safety of the vaccine regimen when given in combination with chemotherapy, and how it affects the immune systems.

Detailed description: CDX-1307 is an experimental vaccine that is designed to generate an immune response against a protein called human chorionic gonadotropin-beta (hCG-β). hCG-β is made by several types of cancers, including bladder cancer, and has been shown to be associated with shorter times to development of metastases and reduced survival in bladder cancer. In this study, it is hoped that administering the CDX-1307 vaccine will cause the body's immune system to attack bladder cancer cells in order to kill them or otherwise keep them from spreading or coming back.

Standard treatment for early stage, muscle invasive bladder cancer includes the administration of chemotherapy to shrink the tumor followed by surgical removal of the bladder (cystectomy).

This study will compare the effect of adding CDX-1307 administration to this standard treatment. CDX-1307 will be given with 3 different immune stimulants to try to increase the immune response against the tumor cells; collectively, this is called the "CDX-1307 vaccine regimen."

Only patients whose tumors make the hCG-β protein will be included in this study. Eligible patients will receive "standard of care" chemotherapy with the CDX-1307 vaccine regimen before surgery, and then CDX-1307 vaccine regimen alone (without chemotherapy) after surgery.

Eligibility criteria: Inclusion Criteria:

Among other criteria, patients must meet all of the following conditions to be eligible to be in the study:

1. 18 years of age or older.
2. Newly diagnosed muscle-invasive transitional cell (urothelial) bladder cancer where neoadjuvant chemotherapy and radical cystectomy with curative intent are indicated (i.e., American Joint Committee on Cancer (AJCC) stage T2-4a, Nany, M0). Patients must be entered into the study within eight weeks of their most recent diagnostic procedure, which is usually a diagnostic biopsy or transurethral resection of bladder tumor (TURBT) procedure.
3. Histopathologically confirmed, transitional cell (urothelial) carcinoma. Urothelial tumors with mixed histology (but with \<50% variant) are eligible.
4. Tumor tissue (obtained during a prior procedure) confirmed to express hCG-β by a central laboratory.
5. Candidate for therapy with neoadjuvant chemotherapy.

Exclusion Criteria:

Among other criteria, patients who meet any of the following conditions are NOT eligible to be in the study:

1. Previous systemic chemotherapy or radiation for bladder cancer. Note: Prior immunotherapy or intravesical (administered within the bladder) chemotherapy for superficial disease is acceptable.
2. History of anaphylactic reaction following exposure to humanized or human therapeutic monoclonal antibodies, hypersensitivity to GM-CSF or yeast derived products, clinically meaningful allergic reactions to imiquimod, resiquimod, or any known hypersensitivity or prior reaction to any of the formulation excipients in the study drugs.
3. Concurrent chronic treatment with immunosuppressive or immunomodulatory agents, including any systemic steroid (exception: inhaled or topically applied steroids, and acute and chronic standard dose NSAIDs, are permitted).
4. Known infection with HIV, HBV or HCV.
5. Any underlying medical condition that, in the Investigator's opinion, will make the administration of study vaccine hazardous to the patient, would obscure the interpretation of adverse events, or would contraindicate receipt of neoadjuvant chemotherapy or surgical resection.

Primary outcomes:
measure: 2 year Recurrence-Free Survival Rate
timeFrame: 2 years following enrollment
measure: Duration of Recurrence-Free Survival
timeFrame: Up-to 4 years after bladder removal surgery (cystectomy)
Secondary outcomes:
measure: Tumor response to neoadjuvant chemotherapy
timeFrame: At cystectomy (anticipated to be about 4 months post-enrollment)
measure: Overall survival
timeFrame: Up-to 4 years following bladder removal surgery (cystecomy)
measure: Safety / Tolerability
timeFrame: Through completion of study treatment (about 1 year post-resection)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: BCG Oncology, PC
state: Arizona
city: La Jolla
country: United States
facility: University of California - San Diego
state: California
city: Los Angeles
country: United States
facility: University of Southern California Norris Comprehensive Cancer Center LA-USC Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky Markey Cancer Center Clinical Research Organization
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Syracuse
country: United States
facility: Syracuse VA Medical Center
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
Study officials:
References: