Phase 2
N=50
Low Dose Arsenic Trioxide as a Potential Chemotherapy Protector
Cancer Other Than Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT01428128 ↗Enrolled (actual)
50
Serious AEs
25.7%
Results posted
Jul 2014
Primary outcome: Primary: Dose of Arsenic That Blocks Activation of p53 — 0.005 mg/kg
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Arsenic Trioxide (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- The University of Texas Health Science Center at San Antonio
- Primary completion
- Jan 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Dose of Arsenic That Blocks Activation of p53 |
0.005 | — |
| SECONDARY Complete Blood Count (CBC) |
— | — |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- 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.
- Present with or without previous treatment for the disease.
- ECOG (Eastern Cooperative Oncology Group) performance status 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 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.
Data sourced from ClinicalTrials.gov (NCT01428128). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.