Phase 2, 2-Part, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of CT-322 Monotherapy and Combination Therapy With Irinotecan in Patients With Recurrent Glioblastoma Multiforme

Inclusion Criteria

DISEASE CHARACTERISTICS

- Histologically confirmed diagnosis of recurrent/progressive GBM presenting in first,
second, or third relapse (progression following anti-cancer therapy other than
surgery)

- Bidimensionally measurable recurrent or residual primary disease on contrast-enhanced
MRI

PATIENT CHARACTERISTICS

Age:

• 18 and over

Hematopoietic:

- ANC ≥ 1,500/mL

- Platelets ≥ 100,000/mL

- Hemoglobin ≥ 9.0g/dL

Hepatic:

- AST and ALT ≤ 1.5 x ULN

- Bilirubin ≤ 1.5 x ULN

Coagulation:

• INR < 1.5 or PT within normal limits; and PTT within normal limits

Renal:

Creatinine ≤ 1.5 x ULN; Urine protein/creatinine ratio ≤ 1

Cardiovascular

- 2-dimensional echocardiogram or cardiac multigated acquisition (MUGA) scan
demonstrating left ventricular ejection fraction within the institutional normal
range.

- No coronary artery bypass graft, angioplasty, vascular stenting, myocardial
infarction, unstable angina, congestive heart failure within the preceding 12 months.

- No thrombotic or embolic cerebrovascular accident, including transient ischemic
attacks within the past 12 months and no conditions that would not permit the safe
discontinuation of specified anti-platelet medications

- No intraparenchymal CNS hemorrhage, except for Grade 1 intraparenchymal hemorrhage in
the immediate post-operative period or Grade 1 intraparenchymal hemorrhage that has
been stable or improved

Immunologic:

• Not known to have human immunodeficiency virus infection (HIV) or active hepatitis B or
C virus infection

Other:

- Negative pregnancy test within 72 hours prior to drug administration

- Not pregnant or breast feeding

- Fertile patients must agree to use effective methods of birth control and must agree
to do so until at least 4 weeks after the last dose of drug administration

- No serious non-healing wound, ulcer or bone fracture or recent significant traumatic
injury (within 4 weeks)

- Have ability to understand and sign an informed consent document

- Be willing and able to comply with scheduled visits, treatment plan, laboratory
tests, and other study procedures

- No other malignancy within the past 3 years, except for basal cell skin cancer,
cervical carcinoma in situ, or other primary malignancy that is not currently
clinically significant or does not require active intervention

- No prior grade 3 or greater toxicity to irinotecan

- No other severe, acute, or chronic medical or psychiatric condition or laboratory
abnormality that could increase the risks associated with study participation or
study drug administration or could interfere with the interpretation of the study
results and would make the patient inappropriate for study entry

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- See Disease Characteristics

- At least 4 weeks between prior biological or immunotherapy and recovered

Chemotherapy:

- See Disease Characteristics

- At least 4 weeks since prior chemotherapy and recovered (6 weeks for nitrosoureas),
unless there is unequivocal evidence of tumor progression

Radiotherapy:

• At least 12 weeks from completion of standard, daily radiotherapy and recovered, unless
any of the following occurs:

- New area of enhancement on MRI that is outside the radiotherapy field

- Biopsy-proven recurrent tumor

- Radiographic evidence of progressive tumor on 2 consecutive scans taken ≥ 4 weeks
apart

Surgery

- At least 4 weeks since major surgery, open biopsy or significant traumatic injury and
recovered

- At least 1 week since other prior biopsy

Other:

- Not concurrently enrolled in another therapeutic clinical trial involving ongoing
therapy

- No prior treatment with VEGF or VEGFR inhibitors or vascular targeting/disrupting
agents

- No prior CT-322 therapy

- No prior failure of irinotecan therapy

- No prior treatment with stereotactic radiosurgery, brachytherapy, or a surgically
created resection cavity to support other anatomically localized therapies

- No severe or uncontrolled medical disease (uncontrolled diabetes, hypertension,
serious infection > CTCAE grade 2, significant bleeding or platelet dysfunction,
gastrointestinal bleed)