Kaposi's Sarcoma Trial Recruiting: TNP-470 (AGM-1470), New Kind of Treatment

A new kind of treatment for Kaposi's sarcoma (KS) has now
begun human testing at the U. S. National Cancer Institute. The
treatment, TNP-470 (formerly called AGM-1470) prevents the growth
of new blood vessels; KS is associated with excessive growth of
blood vessels. The current trial is only for persons with KS;
however, animal studies have suggested that this class of
compounds, called angioinhibins, could also be important for
treating many kinds of solid-tumor cancers. [For background on
TNP-470, see "Angiogenesis Inhibitors -- New Approach to Cancer,
KS Treatments," AIDS TREATMENT NEWS #135, September 20, 1991.]

Volunteers must:

* be HIV positive;

* have KS but no evidence of pulmonary or gastrointestinal KS;

* be ambulatory and at least well enough to care for themselves;
and

* be on a stable dose of antiretroviral therapy for at least a
month.

Also, because the drug has caused small hemorrhages in
animals at very high doses, this trial has strict exclusion
criteria for hematological abnormalities, including hemoglobin
less than 9, ANC less than 1,000, platelets less than 100,000, or
APTT or PT greater than 120 percent of normal, or known bleeding
disorders. Persons are also excluded if they have pulmonary KS,
actively bleeding or critically located KS, or life-threatening
KS which is responsive to other treatments. Other exclusions are
grade 2 or greater peripheral neuropathy from any cause, seizures
in the last 10 years, any cancer except completely removed basal
cell carcinoma of the skin, active severe or life-threatening
infection, or KS treatment in the last three weeks with
chemotherapy, interferon, radiation, steroids, or any local KS
treatment such as intralesional injections. There are other
entry criteria, but the ones listed above are most likely to
exclude potential volunteers. Because this is the first human
trial of the drug, the entry criteria are strict both to reduce
the danger to the volunteers and to allow the most scientific
knowledge to be obtained; future trials will probably have less
severe restrictions.

As this article goes to press, two volunteers are enrolled;
as many as 48 will be recruited. The drug is given
intravenously, during one hour, every other day. Eight dosage
levels will be tested (from 4.6 to 76.3 mg per meter squared
every other day), with three to six patients at each level,
unless toxicity prevents the higher doses from being tried. The
reason for the schedule with the two-week break is that new drugs
are not usually tested in humans for longer than the animal
toxicity trials have run, in this case four weeks; the FDA
allowed a six-week test after the break, since there was no
evidence of any cumulative toxicity in the animals.

Arrangements

Volunteers will probably need to stay near Washington, D. C.
for most of the 12 weeks of the trial. (The 12 weeks includes a
two-week rest period, after the first four weeks, during which
volunteers from outside the Washington area can go home.) For
the first two weeks of receiving the drug, each volunteer will be
an inpatient at the Clinical Center of the National Institute of
Health, in order to allow careful medical monitoring. For the
rest of the time, living expenses can be partially covered for
those from outside the Washington area. Persons must pay their
own expenses for traveling to NIH for the first time to be
evaluated for this trial; after they are accepted as NIH
patients, NIH will pay transportation to and from home, in
addition to the living expenses.

For information about volunteering for this trial, call
Sergio Bauza, R. N., or Kathleen Wyvill, R. N., at the National
Cancer Institute, 301/496-8959, or James Pluda, M. D., 301/496-
8398.