A study for patients who have failed standard therapy. If there is no dose limiting
toxicities the patients will receive further cycles of therapy if there is no evidence of
This is a non-randomized, open-label, Phase I study. A modified Fibonacci dose escalation
will be used to determine the MTD for subsequent Phase II trials. Study duration is
expected to be 12 to 18 months. Patients with a histological or cytological diagnosis of a
solid tumor who have failed standard therapy or for whom no standard therapy exists are
enrolled. If there is no dose limiting toxicities and if patients meet the inclusion
criteria and have none of the exclusion criteria of the protocol, they will receive further
cycles of therapy if there is no evidence of disease progression.
- Adult patients at least 18 years of age.
- All patients must have an advanced solid tumor that has failed standard therapy or
for which no standard therapy exists.
- Histological or cytological diagnosis of a malignant solid tumor.
- Measurable or non-measurable disease.
- Any chemotherapy, radiotherapy, or major surgery at least 4 weeks prior to study
entry (6 weeks for nitrosoureas or mitomycin C). Patients must have recovered from
the toxic effects of any prior therapy.
- Karnofsky performance status index greater than or equal to 80.
- Must have adequate organ and immune system function according to the study design,
obtained less than or equal to 7-days prior to treatment with NM-3.
- Female patients of childbearing potential must have a negative serum pregnancy test
within 7 days of study enrollment. Men and women with reproductive potential must
use an effective contraceptive method while enrolled in this study and for 3 months
after the patient has completed study.
- Patient must be able to swallow.
- Signed, written informed consent from patient or guardian.
- Estimated life expectancy of at least 12 weeks.
- Known sensitivity to study drug or its analogs.
- Treatment with any investigational therapy within the preceding 4 weeks.
- Patients with hematological malignancies including leukemia, lymphoma, or multiple
- Active and uncontrolled infection.
- Psychiatric disorders, alcohol or chemical abuse that would interfere with consent or
- Uncontrolled congestive heart failure or angina.
- Pregnancy or lactation.
- Any other severe concurrent disease, which as judged by the investigator, would make
the patient inappropriate for entry into this study.
- Patients with active gastrointestinal bleeding or ulceration, unhealed wounds or
- Patients who are on anticoagulant therapy or taking aspirin, nonsteroidal
anti-inflammatory drugs, unfractionated heparin, low molecular weight heparin,
danaproid, thrombolytic agents, anti-platelet antibodies, glycoprotein IIb, IIIa
antagonists, H2 blockers, or proton pump inhibitors.
- Brain or leptomeningeal metastases.
- Patients known to be HIV positive or who have an AIDS-related illness.
- Patients with a history of gastrointestinal bleeding from varices, arteriovenous
malformations, Osler Weber Rendu syndrome, polyps, prior surgery, or gastric
ulcerations. Patients who had bleeding not associated with a coagulopathy after
surgery or gastric ulceration and who have no further bleeding or recurrence of their
ulcers for more than one year are eligible for this study.
- Patients with a total accumulated doxorubicin or equivalent dose over 450 mg/m2.
- Patients with more than 1 risk factor, where a risk factor is defined as any one of
the following (1-7):1. prior anthracyclines larger than 300 mg/m2 doxorubicin
equivalent.2.mediastinum/left breast irradiation. 3.history of arterial hypertension
(systolic blood pressure greater than 140 or diastolic blood pressure greater than
90, or receiving anti-hypertensive treatment).4. obesity (body mass index
(BMI)).5. diabetes mellitus (fasting plasma glucose level greater than 126 mg/dL
American Diabetes Association (ADA) guidelines).6. smoking (any smoking in the month
prior to study entry).7. hypercholesterolemia (greater than 240 mg/dL).