Ganitumab and Gemcitabine Hydrochloride Followed by Radiation Therapy, Ganitumab, Capecitabine, and Maintenance Therapy in Treating Patients With Locally Advanced Cancer of the Pancreas
RATIONALE: Monoclonal antibodies, such as ganitumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as gemcitabine hydrochloride and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Specialized radiation therapy, such as 3-dimensional conformal radiation therapy, that delivers a high-dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.
PURPOSE: This phase I trial is studying the side effects and best dose of ganitumab when given together with gemcitabine hydrochloride followed by radiation therapy, ganitumab, capecitabine, and maintenance therapy in treating patients with locally advanced cancer of the pancreas.
Drug: gemcitabine hydrochloride
Radiation: 3-dimensional conformal radiation therapy
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Induction AMG 479 and Gemcitabine, Followed by AMG 479, Capecitabine, and 3D-Conformal Radiation Therapy (3D-CRT) With Subsequent Maintenance Therapy for Locally Advanced Pancreatic Cancer|
- Dose-limiting toxicity of ganitumab and capecitabine given concurrently with radiotherapy [ Designated as safety issue: Yes ]
- Adverse events (at any time) according to the NCI CTCAE v. 4 [ Designated as safety issue: Yes ]
- Response rate (for patients treated at maximum-tolerated dose of ganitumab) [ Designated as safety issue: No ]
- Overall survival (for patients treated at maximum-tolerated dose of ganitumab) [ Designated as safety issue: No ]
|Study Start Date:||February 2012|
|Estimated Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
- To evaluate the maximum dose of ganitumab, up to a target dose of 20 mg/kg, given concurrently with capecitabine and radiotherapy following induction ganitumab and gemcitabine hydrochloride in patients with locally advanced pancreatic cancer.
- To evaluate the safety profile of induction therapy comprising ganitumab and gemcitabine hydrochloride, followed by ganitumab and concurrent chemoradiation, and subsequently by maintenance ganitumab and gemcitabine hydrochloride until disease progression in patients with locally advanced pancreatic cancer.
- To evaluate response and overall survival of patients treated at the maximum dose of ganitumab given concurrently with capecitabine and radiotherapy following induction ganitumab and subsequently followed by maintenance ganitumab and gemcitabine hydrochloride until disease progression.
OUTLINE: This is a multicenter, dose-escalation study of ganitumab followed by an expanded cohort study.
Induction therapy: Patients receive ganitumab IV over 1-2 hours on days 1 and 15 and gemcitabine hydrochloride IV over 30 minutes on days 1, 15, and 22. Treatment repeats every 28 days for 2 courses.
Concurrent therapy: Beginning 10-28 days later, patients undergo 3-dimensional conformal radiotherapy once daily, 5 days a week for 5.5 weeks beginning on day 1. Patients also receive concurrent ganitumab IV over 1-2 hours on days 1, 15, and 29 and capecitabine orally (PO) twice daily on days 1-5 weekly for 5.5 weeks.
Maintenance therapy: Beginning 21-42 days later, patients receive ganitumab IV over 1-2 hours on days 1 and 15 and gemcitabine hydrochloride IV over 30 minutes on days 1, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 3 months for 2 years, every 4 months for 1 year, and then annually thereafter.
|United States, California|
|St. Joseph Hospital Regional Cancer Center - Orange|
|Orange, California, United States, 92868|
|United States, Delaware|
|CCOP - Christiana Care Health Services|
|Newark, Delaware, United States, 19713|
|United States, Kentucky|
|James Graham Brown Cancer Center at University of Louisville|
|Louisville, Kentucky, United States, 40202|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|United States, New York|
|James P. Wilmot Cancer Center at University of Rochester Medical Center|
|Rochester, New York, United States, 14642|
|United States, Ohio|
|Summa Center for Cancer Care at Akron City Hospital|
|Akron, Ohio, United States, 44309-2090|
|United States, Pennsylvania|
|McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center|
|Reading, Pennsylvania, United States, 19612-6052|
|United States, Rhode Island|
|Northmain Radiation Oncology|
|Providence, Rhode Island, United States, 02904|
|Rhode Island Hospital Comprehensive Cancer Center|
|Providence, Rhode Island, United States, 02903|
|United States, Texas|
|M. D. Anderson Cancer Center at University of Texas|
|Houston, Texas, United States, 77030-4009|
|Principal Investigator:||Christopher H. Crane, MD||M.D. Anderson Cancer Center|