A Phase I, Open-Label, Multi-center, Competitive Enrollment and Dose-escalation Study of ALT-836 in Combination With Gemcitabine for Locally Advanced or Metastatic Solid Tumors

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed

- Locally advanced or metastatic non-hematologic malignancies

- Measureable

- Refractory to standard therapies or single agent gemcitabine is indicated as a
standard treatment option

PRIOR/CONCURRENT THERAPY:

- No concurrent radiotherapy, chemotherapy, immunotherapy or other investigational
agents

- Must have recovered from side effects of prior therapies

PATIENT CHARACTERISTICS:

Life expectancy

- > 12 weeks

Performance Status

- ECOG 0 or 1

Bone Marrow Reserve

- Absolute Neutrophil count (AGC/ANC) ≥ 1,500/uL

- Platelets ≥ 100,000/uL

- Hemoglobin > 9 g/dL

Renal Function

- Calculated Glomerular filtration rate (GFR) > 59mL/min/1.73M^2

Hepatic Function

- Total bilirubin ≤ 1.5 X ULN

- AST, ALT, and ALP ≤ 3 X ULN or ≤ 5.0 x ULN, if liver metastasis exists

- PT INR ≤ 1.5 X ULN

Cardiovascular

- No history of clinically significant vascular disease

- No New York Heart Association (NYHA) Class > II heart failure

Hematologic

- No history of bleeding disorders

- No evidence of bleeding diathesis or coagulopathy

- No presence of clinically significant hemoptysis or hematuria, presence of serious
non-healing wound or ulceration, or signs of other bleeding

- No evidence of a tumor invasion of any major blood vessel

- No trauma with increased risk of life-threatening bleeding or history of severe head
trauma or intracranial surgery within two months of study entry

Surgery/Procedures

- No major surgery or open biopsy within 28 days before drug infusion or evidence of
active bleeding postoperatively

- No plan for any major surgery during treatment period

- No presence or requirement of an epidural catheter or lumbar puncture within 48 hours
prior to each dose of study treatment

- No anticipation of receiving an epidural catheter or a lumbar puncture within 48
hours after each dose of study treatment

Excluded Medications or Treatment Regimens

- Unfractionated heparin of > 15,000 units/day within 8 hours prior to each dose of
study treatment

- Low-molecular weight heparin at a higher dose than recommended for prophylactic used
or required within 20 hours prior to each dose of study treatment

- Warfarin used or required within 48 hours prior to each dose of study treatment and
the prothrombin time (INR) exceeded the upper limit of normal range

- Direct thrombin inhibitors or Xa inhibitors

- Acetylsalicylic acid used or required within 72 hours prior to each dose of study
treatment

- Clopidogrel bisulfate used or required within 48 hours prior to each dose of study
treatment

- Anticipated requirement for anti-platelet or anti-coagulant agents excluding
non-aspirin NSAID within 48 hours following study treatment infusion

Other

- No active systemic infection requiring parenteral antibiotic therapy

- No history of or presence of a CNS disease

- No history of allergic reactions to compounds of similar chemical or biologic
composition

- Not HIV positive

- No women who are pregnant or nursing

- A negative serum pregnancy test if female

- Patients, both females and males, with reproductive potential must agree to use
effective contraceptive measures for the duration of the study

- No history of significant renal, endocrinologic, metabolic, immunologic or hepatic
disease

- No evidence of psychiatric illness/social situations

- Other illness that in the opinion of the investigator would exclude the patient from
participating

- Must provide informed consent and HIPAA authorization and comply with
protocol-specified procedures and follow-up evaluations