A Phase I, Multi-Dose Study of RAV12 (ANTI-RAAG12 MAB) in Patients With Metastatic or Recurrent Adenocarcinoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma

- Metastatic or recurrent disease

- Not curable by standard therapies

- Must have failed at least 1, but no more than 3, prior therapies for metastatic or
recurrent disease

- Patients with colorectal or breast adenocarcinoma must have failed at least 2
prior therapies

- Must have had at least stable disease for 3 months while on last treatment prior
to most recent disease progression

- Meets 1 of the following criteria:

- At least 1 measurable site of disease ≥ 2 cm by radiography

- Evaluable disease that could be reliably and consistently followed, as deemed by
the principal investigator

- RAAG12 expression confirmed* by immunohistochemistry NOTE: *Not required for patients
with colon, pancreatic, or gastric adenocarcinoma

- No evidence of residual or recurrent CNS metastases

- Hormone receptor status:

- Not specified

PATIENT CHARACTERISTICS:

Age

- 18 and over

Sex

- Not specified

Menopausal status

- Not specified

Performance status

- ECOG 0-1

Life expectancy

- More than 3 months

Hematopoietic

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9.0 g/dL (transfusions allowed)

- Absolute neutrophil count ≥ 1,500/mm^3

Hepatic

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- γ-glutamyl transferase ≤ 2.5 times ULN

- Adequate hepatic function sufficient to undergo study therapy

Renal

- Creatinine < 1.5 mg/dL

- Adequate renal function sufficient to undergo study therapy

Cardiovascular

- No New York Heart Association class III or IV heart disease

- No thrombosis within the past 3 months, including any of the following:

- Deep vein thrombosis

- Myocardial infarction

- Stroke

- Adequate cardiac function sufficient to undergo study therapy

Pulmonary

- No pulmonary embolism within the past 3 months

- No significant pulmonary compromise, particularly dependence on supplemental oxygen
on an as-needed or continuous basis

- Adequate pulmonary function sufficient to undergo study therapy

Immunologic

- No active viral, bacterial or systemic fungal infection requiring parenteral therapy
within the past 4 weeks

- No history of chronic or recurrent infection requiring continual antiviral,
antifungal, or antibacterial agents

- No known hypersensitivity to murine or recombinant proteins, polysorbate 80, or any
excipient contained in study drug

Other

- Amylase and lipase normal

- No other primary malignancy within the past 3 years except for the following:

- Treated non-melanoma skin cancer

- Carcinoma in situ of the cervix by biopsy

- Squamous intraepithelial lesion of the cervix by PAP smear

- Localized prostate cancer (Gleason score < 6)

- Resected melanoma in situ

- No other serious medical condition that would preclude study participation

- No dementia or altered mental status that would preclude giving informed consent

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after study
participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- At least 3 half-lives since prior monoclonal antibody therapy

- No concurrent vaccinations

- No concurrent prophylactic hematologic growth factors

Chemotherapy

- At least 4 weeks since prior chemotherapy

Endocrine therapy

- No concurrent steroids except for the following:

- Inhaled, ophthalmic, or nasal steroids

- Stable dose of oral prednisone (or equivalent) ≤ 10 mg/day

Radiotherapy

- At least 4 weeks since prior radiotherapy

Surgery

- More than 4 weeks since prior major surgery

Other

- More than 4 weeks since prior investigational agents

- Prior oral antiviral, antifungal, or antibacterial therapy allowed provided therapy
was completed within the past week

- No other concurrent antineoplastic therapy

- No concurrent immunosuppressive medications

- No other concurrent investigational agents

- No concurrent vitamins except those approved by the medical monitor

- Concurrent daily multivitamin allowed

- Concurrent bisphosphonates allowed provided patient is on stable dose for ≥ 1 month
prior to study entry