Low Dose Arsenic Trioxide as a Potential Chemotherapy Protector
Many types of cancer are treated with chemotherapy drugs and/or radiation therapy. These forms of treatment, however, can also damage normal (non-cancer) cells and cause a variety of side effects. There are many side effects of chemotherapy. A few examples are: lowered red blood cell counts (anemia) which can lead to tiredness, weakness or shortness of breath; lowered white cell counts (white blood cells which help the body to fight infection); low platelet counts (platelets help blood to clot); nausea and vomiting; diarrhea; lip and mouth sores and hair loss. These side effects can range from mild to severe. P53 is a protein in the body that regulates the cell cycle. If a cell becomes damaged from chemotherapy or radiation treatment, the p53 protein becomes activated. This activation can cause the cell to die and is involved in causing side effects from chemotherapy or radiation therapy.
Arsenic trioxide is a drug that is currently approved by the FDA (Food and Drug Administration) for the treatment of acute promyelocytic leukemia (APL), which is a type of blood and bone marrow cancer. It is given by I.V (intravenous, by vein). New preclinical studies have shown that when given in smaller than normal doses before treatment with chemotherapy and/or radiation therapy, the arsenic trioxide can block the activation of p53 and protect normal tissues from treatment damage. Preclinical means that the studies have been done in a laboratory and not on humans.
This study has two purposes. The first is to find the dose range for arsenic trioxide that will block p53 activity. This dose has been determined from the first five subjects who took part in the study and received arsenic trioxide. The dose of arsenic trioxide for this study is about 1/30 of the normal dose given when arsenic trioxide is used to treat acute promyelocytic leukemia. The second is to see if the arsenic trioxide will decrease the side effects of chemotherapy. In this study, arsenic trioxide is investigational. "Investigational" means that arsenic trioxide has not yet been approved by the FDA to block p53 activity.
This study will help find out what the smallest (best) dose is that can be given and the effects, good and/or bad, this drug has on people who take it. The safety of this drug in humans has been tested in prior research studies; however, whether the side effects will still be present at this lower dose is not yet known.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Low Dose Arsenic Trioxide in Patients With Malignancies as a Potential Chemotherapy Protector|
- Decrease in p53 protein production [ Time Frame: Day 1 of chemotherapy ] [ Designated as safety issue: No ]A main objective of this trial is to find the dose of arsenic that blocks the activation of p53. Blocakage will reduce the amount of p53 production as measured by Western Blot.
- complete blood count (CBC) [ Time Frame: Day 9 of chemotherapy ] [ Designated as safety issue: Yes ]Another objective of this trial is to assess if arsenic protects the blood counts that are adversely affected by chemotherapy
|Study Start Date:||April 2011|
|Study Completion Date:||January 2013|
|Primary Completion Date:||January 2013 (Final data collection date for primary outcome measure)|
|Experimental: Arsenic Trioxide||
Drug: Arsenic Trioxide
IV; 0.005mg/kg. Infusion on Days -3, -2 and -1 of Chemo Cycles 2, 4, and 6 (if more than 4 cycles received).
Other Name: Brand name: Trisonex
|United States, Texas|
|The University of Texas Health Science Center at San Antonio|
|San Antonio, Texas, United States, 78229|
|Principal Investigator:||Chul S. Ha, M.D.||The University of Texas Health Science Center at San Antonio|