Low Dose Arsenic Trioxide as a Potential Chemotherapy Protector
Status: | Completed |
---|---|
Conditions: | Blood Cancer |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 12/15/2017 |
Start Date: | April 2011 |
End Date: | January 2013 |
A Phase II Study of Low Dose Arsenic Trioxide in Patients With Malignancies 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.
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.
Inclusion Criteria:
1. Patients ≥ 18 years of age with the diagnosis of malignancy other than leukemia who
are to start chemotherapy known to suppress peripheral blood counts. The expected
interval between each cycle of chemotherapy should be a minimum of 2 weeks. The
minimum number of planned chemotherapy cycles should be 4. Radiation therapy during
chemotherapy is allowed as long as less than 10% of the total bone marrow is radiated.
2. Present with or without previous treatment for the disease.
3. ECOG (Eastern Cooperative Oncology Group) performance status = 2 (see Appendix B).
4. Life expectancy of greater than 6 months
5. Organ functions as deemed appropriate for chemotherapy per standard of care
6. Agree to use adequate contraception prior to study entry and for the duration of study
participation.
7. Ability to understand and the willingness to sign a written informed consent document.
8. No baseline p53 activation in peripheral lymphocytes in culture but p53 activation
should be inducible upon radiation with 2 Gy in culture
Exclusion Criteria:
1. History of allergic reactions attributed to Arsenic Trioxide
2. Experiencing uncontrolled inter-current illness including, but not limited to, ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements.
3. Pregnant
4. HIV-positive patients and taking combination antiretroviral therapy.
5. History of having circulating malignant cells if the patient has lymphoma or myeloma
6. Impaired cardiac function or clinically significant cardiac diseases, including any of
the following: history of long QT syndrome; mean QTc (corrected QT interval) > 500
msec on screening EKG; history of clinically manifest ischemic heart disease including
myocardial infarction; stable or unstable angina, coronary arteriography or cardiac
stress testing/imaging with findings consistent with coronary occlusion or infarction
< 6 months prior to study start; history of heart failure or left ventricular (LV)
dysfunction (LVEF < 45%) by MUGA or ECHO; clinically significant EKG abnormalities
including one or more of the following: left bundle branch block (LBBB), right bundle
branch block (RBBB) with left anterior hemiblock (LAHB). ST segment elevations or
depressions > lmm, or 2nd (Mobitz 11) or 3rd degree AV block; history or presence of
atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular
tachycardia or Torsades de Pointes; other clinically significant heart disease (e.g.
congestive heart failure, uncontrolled hypertension, history of labile hypertension,
or history of poor compliance with an antihypertensive regimen); clinically
significant resting bradycardia (< 50 beats per minute); obligate use of a cardiac
pacemaker.
We found this trial at
1
site
4502 Medical Drive
San Antonio, Texas 78284
San Antonio, Texas 78284
(210) 567-7000

University of Texas Health Science Center at San Antonio The University of Texas Health Science...
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