CT-322 in Treating Patients With Recurrent Glioblastoma Multiforme and Combination Therapy With Irinotecan

Study Overview
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Brief Summary
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RATIONALE: CT-322 may stop the growth of glioblastoma multiforme by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving CT-322 together with irinotecan may kill more tumor cells. PURPOSE: This phase 2 trial is studying the side effects, tolerability, and efficacy of CT-322 when given alone and in combination with irinotecan to patients with glioblastoma multiforme.

Official Title
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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

Conditions
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Brain and Central Nervous System Tumors, Recurrent Glioblastoma Multiforme

Intervention / Treatment
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* Drug: CT-322
* Drug: irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>CT-322 | Drug: CT-322<br>* IV solution, weekly<br>|
| Experimental: 2<br>CT-322 and irinotecan hydrochloride | Drug: CT-322<br>* IV solution, weekly<br>Drug: irinotecan hydrochloride<br>* IV solution, biweekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of CT-322 when administered alone or in combination with irinotecan hydrochloride (Part 1) |  | 15 ± 5 days post the last dose of study drug | 
| Progression-free survival at 6 months (Part 2) |  | Measured upon initiation of cycles 2, 3, 5, 7, 9, 11, and end of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the plasma pharmacokinetics of CT-322 (Cmax, Tmax, AUC, T-HALF) derived from plasma concentration vs time for CT-322 given alone and in combination with irinotecan |  | Part 1: cycle 1, days 1-3, day 5 or 6, days 8, 15, and 22; cycles 2-4, 6, 9, and 12, day 1; EOS and follow up visits. Part 2: cycle 1, days 1, 8, 15, and 22; cycles 2-4, 6, 9, and 12, day 1; EOS and follow up visits. | 
| To assess the presence of anti CT-322 antibodies |  | Part 1: cycle 1, days 1 and 15; cycles 2-4, 6, 9, and 12, day 1; EOS and follow up visits. Part 2: cycle 1, days 1 and 15; cycles 2-4, 6, 9, and 12, day 1; EOS and follow up visits. | 
| To assess the biological activity of CT-322 as measured by plasma biological markers and neuroimaging |  | Part 1: cycle 1, days 1, 2, 8, 15 and 22; cycles 2-4, 6, 9, and 12, day 1; EOS visit. Part 2: cycle 1, days 1, 8, 15 and 22; cycles 2-4, 6, 9, and 12 EOS visit. |