Proton w/FOLFIRINOX-Losartan for Pancreatic Cancer
This is a Phase II clinical trial, which tests the safety and effectiveness of an investigational combination of drugs to learn whether the combination of drugs works in treating a specific cancer. "Investigational" means that the combination of drugs is being studied. It also means that the FDA has not yet approved it for your type of cancer. Proton beam radiation therapy is an FDA approved radiation delivery system.
Conventional radiation therapy uses photons to treat cancer before patients undergo surgery to remove the tumor. In this study we are using radiation with protons, which spares surrounding tissue and organs from radiation. Proton radiation delivers radiation to the area requiring radiation with no dose beyond the treatment area. This may reduce side effects that patients would normally experience with conventional radiation therapy.
Researchers in the laboratory have discovered pathways inside cancer cells which contribute to the growth and survival of tumors. The FOLFIRINOX chemotherapy regimen is a combination of the drugs 5-fluorouracil, leucovorin and oxaliplatin. These chemotherapy drugs, along with the chemotherapy drug capecitabine, work by blocking these pathways and thereby preventing tumor growth. Capecitabine is FDA approved to be used alone or with other drugs to treat other types of advanced cancer, but not pancreatic cancer. In past research studies, FOLFIRINOX followed by radiation therapy with capecitabine has been identified as the most effective and active chemotherapy for patients with cancer that is spreading, and this is why we are using it to treat your type of cancer.
Losartan is classified as an angiotensin-receptor blocker (ARB), and is FDA approved for use in people with high blood pressure. Recent studies in people with different types of cancer, including pancreatic cancer, have shown that combining chemotherapy drugs with an ARB can help reduce/stop tumor growth more effectively than chemotherapy alone. Losartan has been used in previous research studies, and information from those research studies suggests that this drug in combination with FOLFIRINOX and capecitabine may be better at treating your type of cancer.
In this research study, we seek to determine whether combining FOLFIRINOX with Losartan before proton radiation therapy will be more efficient at controlling the growth of or shrinking your tumor than just FOLFIRINOX alone.
Radiation: Proton Beam Radiation
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Feasibility Study of FOLFIRINOX-Losartan Followed by Accelerated Short Course Radiation Therapy With Proton Beam for Locally Advanced Pancreatic Cancer|
- Feasibility of combining FOLFIRINOX-Losartan [ Time Frame: 2 years ] [ Designated as safety issue: No ]To determine the feasibility of the combination of FOLIRINIOX-Losartan in patients with locally advanced unresectable pancreas cancer determining the proportion free of radiographic progression at the time of restaging and consideration of proton therapy after induction chemotherapy
- Progression-Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]To determine the progression free survival of patients with locally advanced disease who receive FOLFIRINOX-Losartan and proton beam radiation therapy
- Overall Survival for FOLFIRINOX + Proton Beam Radiation [ Time Frame: 2 years ] [ Designated as safety issue: No ]To determine overall survival in patients treated with preoperative FOLFIRINOX and proton beam radiation therapy
- Overall Survival for FOLFIRINOX Without Proton Radiation [ Time Frame: 2 years ] [ Designated as safety issue: No ]To determine the overall survival of patients with locally advanced disease who receive FOLFIRINOX-Losartan without proton radiation (i.e. patients who demonstrate progression at restaging)
- Determine Toxicity FOLFIRINOX-Losartan [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]To determine the toxicity of FOLFIRINOX-Losartan in patients with locally advanced pancreatic disease
- Determine Toxicity of FOLFIRINOX-Losartan and Proton Beam Radiation [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]To determine the toxicity of FOLFIRINOX-Losartan and proton beam radiation in patients with locally advanced pancreatic cancer.
- Rate of Downstaging [ Time Frame: 2 years ] [ Designated as safety issue: No ]To determine the rate of downstaging to surgical resection of FOLFIRINOX-Losartan followed by proton radiation in patients with locally advanced pancreatic cancer
- Determine correlation of Somatic Gene Mutations and Outcome [ Time Frame: 2 years ] [ Designated as safety issue: No ]To determine the correlation between a panel of somatic genetic mutations (SNaPSHOT) and outcome in locally advanced pancreatic cancer treated with FOLFIRINOX-Losartan +/- proton beam radiation/capecitabine
- Determine Correlation Between Circulating Biomarkers and Outcome [ Time Frame: 2 years ] [ Designated as safety issue: No ]To determine the correlation between circulating biomarkers of TGF-B1 downregulation, including circulating Collagen I levels, and outcome in locally advanced pancreatic cancer treated with FOLFIRINOX-Losartan +/- proton beam radiation/capecitabine.
- Describe quality of life, symptom burden and mood [ Time Frame: 2 years ] [ Designated as safety issue: No ]Describe quality of life, symptom burden and mood in the study population
- To measure utilization of health services [ Time Frame: 2 years ] [ Designated as safety issue: No ]To measure utilization of health services (ER, hospital and ICU visits) in the study population
|Study Start Date:||July 2013|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Experimental: Experimental Arm
FOLFIRINOX, Losartan, Proton Beam Radiation Therapy
Oxaliplatin via IV on Day 1 over 2 hours; Irinotecan via IV on Day 1 over 90 minutes, 5FU via IV on Day 1 over 2-4 minutes
Other Names:Drug: Losartan
Taken orally every day during Phase I for all 8 cyclesRadiation: Proton Beam Radiation
30-45 minutes per day, daily Monday-Friday
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01821729
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02214|
|Principal Investigator:||Theodore Hong, MD||Massachusetts General Hospital|