A Phase I and Pharmacokinetic Study of NM-3 Administered Orally Once or Twice Daily on Five Consecutive Days and Repeated Weekly for Six Weeks Every Eight Weeks in Patients With Advanced Solid Tumors.
- 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).