Inclusion Criteria

INCLUSION CRITERIA:

All patients with refractory solid tumors and lymphoma are eligible according to the
criteria listed below. Patients with tumor marker evidence of disease only, will not be
eligible for study. A patient must have bone scan evidence of metastatic disease.

Patients must have histopathological documentation of cancer confirmed in the Laboratory
of Pathology/NCI of the Clinical Center at the National Institutes of Health prior to
starting this study.

Patients must have clinically progressive disease documented prior to entry. Progression
must be documented by at least one of the following parameters: two consecutively rising
tumor marker levels, and/or at least one new metastatic deposit on Tc-99 bone
scintigraphy, and/or progression of soft tissue metastases as measured by appropriate
modalities (i.e., imaging, palpation), and/or development of new area of malignant disease
(measurable or evaluable).

Patients must have failed therapy of proven efficacy for their disease. Patients with
metastatic melanoma, non-small cell lung cancer, and renal cell carcinoma will be eligible
without receiving prior therapy. Initial treatment of the non-chemotherapy responsive
malignancies (e.g., disseminated gastrointestinal, noncolorectal cancer) may be done at
the discretion of the investigators.

Patients must be ECOG performance status of less than or equal to 2.

Patients must have a life expectancy of more than three months.

Hematological eligibility parameters (within 1 week of starting therapy): Granulocyte
count greater than or equal 1,500/mm3; Hemoglobin greater than or equal to 9.0 g/dL
(pre-treatment transfusion is allowed, provided the hemoglobin is maintained for more than
30 days and/or active source of bleeding is identified and treated); Platelet count is
greater than or equal to 120,000/mm3; If the creatinine is greater than 1.5 mg/dL, obtain
a 24 hour urine collection. Creatinine clearance must be greater than 60 mL/min; Hepatic
function: normal bilirubin (total); ALT is less than 2.5 times the normal; AST is less
than 2.5 times the normal.

Patients must have recovered from any toxicity related to prior therapy, including
surgery.

Patients must be off prior chemotherapy, hormonal therapy, radiation therapy, or
biological therapy for at least 4 weeks prior to initiation of COL-3. Patients who were
receiving mitomycin C, nitrosoureas, or carboplatin must be 6 weeks from the last
administration of chemotherapy. Patients who were receiving suramin must be 3 months from
the last administration. Patients with prostate cancer must continue to receive LHRH
agonist (unless orchiectomy has been done) but must have failed antiandrogen withdrawal.

Patients with prostate cancer that have not undergone surgical castration must continue
treatment with an LHRH agonist. If for some reason the LHRH agonist has been discontinued
prior to entry on the study, then it should be reinstituted and disease progression must
be documented prior to enrollment.

Patients with local complications which require urgent local medical therapy are not
eligible, but may become so after resolution of the acute problem (i.e., severe bone pain,
spinal cord compression, urinary flow obstruction, etc.).

Patients must not have an acute, critical illness, including a serious untreated
infection. Ureteral stents, or foley catheter, although often colonized, are not a
contraindication to enrollment.

Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial
infarction (within 6 months of enrollment), New York class II-IV congestive heart failure,
chronic obstructive lung disease requiring oxygen therapy or uncontrolled seizure activity
are not eligible.

Patients must be willing to travel from their home to the NIH for follow-up visits.

All patients of childbearing capability will be required to use contraception during
treatment and for two months after the completion of COL-3 treatment. All females
patients of childbearing potential will have a negative pregnancy test.

Patients must be able to understand and sign the attached informed consent form.

Patients must be older than or 18 years of age.

Although prior radiation therapy to the primary, or a metastatic lesion, does not exclude
an individual from this study, it does exclude that lesion from the optional biopsy.
Thus, if an individual has a primary lesion which has been radiated, then they can not
participate in that portion of the study.

EXCLUSION CRITERIA:

Active infection, including positive serology for HIV. Colonized urinary tract
instrumentation is not excluded.

Patients with brain metastases or primary CNS malignancies.

Concurrent therapy for their cancer (i.e., radiation therapy, chemotherapy, etc.).

Patients who are pregnant or lactating. No data is currently available about the
excretion of COL-3 in breast milk. Also, no toxicity data in gestating animals exists at
the present time. Until data of this nature becomes available, we will exclude patients
who are pregnant or lactating.

Patients who are known to be HIV positive will not be eligible for this protocol. Since
COL-3 is a known inhibitor of neutrophil gelatinase, HIV patients will be excluded because
of their increased risk of infection. HIV testing will be required.

Patients who are currently taking anticonvulsants (phenobarbital, phenytoin,
carbamazepine). Patients taking rifampin will also be excluded. There is a potential
drug interactions between COL-3 and these classes of drugs.