Low Dose Arsenic Trioxide as a Potential Chemotherapy Protector
Condition: Cancer Other Than Leukemia
Intervention: Arsenic Trioxide
Intervention description: IV; 0.005mg/kg. Infusion on Days -3, -2 and -1 of Chemo Cycles 2, 4, and 6 (if more than 4 cycles received).
Intervention MeSH terms: Arsenic Trioxide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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:

          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.