Cancer Other Than Leukemia
Conditions
Brief 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.
Interventions
DRUGArsenic 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).
Sponsors
The University of Texas Health Science Center at San Antonio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose of Arsenic That Blocks Activation of p53 | Day 1 of chemotherapy | A main objective of this trial is to find the dose of arsenic that blocks the activation of p53. Blockage will reduce the amount of p53 production as measured by Western Blot. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Blood Count (CBC) | Day 9 of chemotherapy | Another objective of this trial is to assess if arsenic protects the blood counts that are adversely affected by chemotherapy |
Countries
United States
Participant flow
Recruitment details
Recruitment took place from April 2011 to November 2012. Patients were recruited from Medical Oncology clinic and due to receive standard of care chemotherapy.
Pre-assignment details
No baseline p52 activation in peripheral lymphocytes in culture, but p53 activation inducible upon radiation in culture.
Participants by arm
| Arm | Count |
|---|---|
| Arsenic Trioxide 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). | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Received Neulasta in one cycle | 2 |
| Overall Study | Screen failure by p53 | 10 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Arsenic Trioxide |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Age, Continuous | 52 years |
| Region of Enrollment United States | 33 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 35 / 35 |
| serious Total, serious adverse events | 9 / 35 |
Outcome results
Primary
Dose of Arsenic That Blocks Activation of p53
A main objective of this trial is to find the dose of arsenic that blocks the activation of p53. Blockage will reduce the amount of p53 production as measured by Western Blot.
Time frame: Day 1 of chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arsenic Trioxide | Dose of Arsenic That Blocks Activation of p53 | 0.005 mg/kg |
Secondary
Complete Blood Count (CBC)
Another objective of this trial is to assess if arsenic protects the blood counts that are adversely affected by chemotherapy
Time frame: Day 9 of chemotherapy
Population: Data was not collected from CBC at 9 days