A Study of the CDX-1307 Vaccine Regimen in Patients With Newly Diagnosed Muscle-Invasive Bladder Cancer (The "N-ABLE" Study)

Bladder Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01094496
• Other study ID #: CDX1307-03
• Status: Terminated
• Phase: Phase 2
• Start date: April 2010
• Est. completion date: July 2011

Study information

• Verified date: February 2016
• Source: Celldex Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-ß 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.

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Biological:
• CDX-1307 Vaccine Regimen
CDX-1307 vaccine co-administered with immune adjuvants (GM-CSF, Poly-ICLC and Resiquimod)

Drug:
• Chemotherapy

Locations

Country	Name	City	State
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland
United States	Roswell Park Cancer Center	Buffalo	New York
United States	Henry Ford Health System	Detroit	Michigan
United States	University of Florida	Gainesville	Florida
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of California - San Diego	La Jolla	California
United States	University of Kentucky Markey Cancer Center Clinical Research Organization	Lexington	Kentucky
United States	University of Southern California Norris Comprehensive Cancer Center LA-USC Medical Center	Los Angeles	California
United States	Weill Cornell Medical College	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	BCG Oncology, PC	Phoenix	Arizona
United States	University of Rochester	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Syracuse VA Medical Center	Syracuse	New York
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Celldex Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	2 year Recurrence-Free Survival Rate	The 2-year recurrence-free survival rate will be estimated based on the proportion of patients who are classified as alive and without documented disease recurrence at this time point.	2 years following enrollment
Primary	Duration of Recurrence-Free Survival	The duration of recurrence-free survival is defined as the number of months from enrollment to the earlier of disease recurrence or death (whatever the cause).	Up-to 4 years after bladder removal surgery (cystectomy)
Secondary	Tumor response to neoadjuvant chemotherapy	The tumor response to neoadjuvant chemotherapy will be evaluated as the proportion of patients who achieve a radiographic response as defined by the Response Evaluation Criteria for Solid Tumors (RECIST 1.1) or a pathologic complete response at cystectomy.	At cystectomy (anticipated to be about 4 months post-enrollment)
Secondary	Overall survival	Overall survival is defined as the number of months from enrollment to the date of death (whatever the cause).	Up-to 4 years following bladder removal surgery (cystecomy)
Secondary	Safety / Tolerability	The number and percentage of patients experiencing one or more adverse events will be summarized by relationship to study drug and severity. Separate tabulations will be provided for the neoadjuvant and adjuvant treatment phases.	Through completion of study treatment (about 1 year post-resection)