Glioblastoma Multiforme

Study drug Pazopanib will be administered once tumoral evaluation has been performed and after Stupp Protocol (TMZ + Radiation) realisation.

Pazopanib

Centre Antoine Lacassagne

Phase I/II Study of Pazopanib+ Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme

A Phase I/II Study of Pazopanib in Combination With Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme After Surgery and RT-CT

To evaluate the Recommended Phase 2 Dose (RP2D) of pazopanib in oral route in addition to the maintenance phase of the Stupp protocol, regarding the toxicities that should not be more than 33 %

To define the overall tolerance of pazopanib associated with TMZ during the maintenance phase of the "Stupp protocol" regarding biological toxicities, blood pressure and hemorragic events

To assess the antitumor activity of the adjunction of daily dose of pazopanib to the maintenance phase of the Stupp protocol according to the Revised Assessment in Neuro-Oncology (RANO) criteria (response rate) and the median duration of response.

To determine the median Progression-Free-Survival (mPFS), the PFS rate at 12 (PFS-12) months.

To determine the median Overall Survival (mOS), the OS rate at 6 (OS-6) and 12 (OS-12) months.

To determine the pharmacokinetics (PK) profile of pazopanib when given in combination with TMZ.

To determine the pharmacokinetics (PK) profile of TMZ when given in combination with pazopanib.

GlaxoSmithKline

Gliadel/Avastin/CPT-11

Sex: Female, Male

The percentage of participants surviving 24 weeks from the start of study treatment

24-week Overall Survival

The percentage of participants surviving 24 weeks from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to modified Macdonald criteria, or to death due to any cause.

24-week Progression-free Survival (PFS)

Time in months from the start of study treatment to the date of first progression according to modified Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.

Gliadel wafers (1-8) inserted at time of gross total resection. CPT-11 (Irinotecan): 125 mg/m2 (no enzyme-inducing anticonvulsant drugs) or 340 mg/m2 (enzyme-inducing anticonvulsant drugs) given every two weeks on days 1, 15, 29 of each 42 day cycle, up to 12 cycles. If the patient has the UGT 1A1 polymorphism (7/7), they do not metabolize the irinotecan normally, so these patients will start out at a two dose level reduction. For patients on an EIAED, the starting dose will be 275 mg/M2, and for patients not on an EIAED, the starting dose will be 75 mg/M2. Avastin: 10 mg/kg immediately after the irinotecan given every 2 weeks on days 1, 15, 29 of each 42 day cycle.

Median Progression-free Survival (PFS)

Time in months from the start of study treatment to date of death due to any cause. Patients alive at last follow-up are censored as of that follow-up date. Median OS was estimated using a Kaplan-Meier curve.

Median Overall Survival (OS)

Incidence and Severity of Central Nervous System (CNS) Hemorrhage

Incidence of grade ≥ 4 hematologic and ≥ grade 3 non-hematologic toxicities

Incidence of Grade ≥ 4 Hematologic and ≥ Grade 3 Non-hematologic Toxicities

Gliadel wafers (1-8) inserted at time of gross total resection. CPT-11 (Irinotecan): 125 mg/m2 (no enzyme-inducing anticonvulsant drugs) or 340 mg/m2 (enzyme-inducing anticonvulsant drugs) given every two weeks on days 1, 15, 29 of each 42 day cycle, up to 12 cycles. If the patient has the uridine diphosphate (UDP) glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) polymorphism (7/7), they do not metabolize the irinotecan normally, so these patients will start out at a two dose level reduction. For patients on an enzyme-inducing anti-epileptic drugs (EIAED), the starting dose will be 275 mg/M2, and for patients not on an EIAED, the starting dose will be 75 mg/M2. Avastin: 10 mg/kg immediately after the irinotecan given every 2 weeks on days 1, 15, 29 of each 42 day cycle.

Overall Study

Annick Desjardins, MD, FRCPC

Malignant Glioma

Gliosarcoma

Duke University Medical Center Clinical Trials

The Preston Robert Tisch Brain Tumor Center

Duke University Medical Center

A Study of Gliadel Followed by Avastin + Irinotecan for Glioblastoma Multiforme (GBM)

Phase II Trial for Patients With Glioblastoma Multiforme (GBM) Treated With Gliadel Followed by Avastin Plus Irinotecan

Duke University

Eisai Inc.

Genentech, Inc.

Bevacizumab 15 mg/kg every 3 weeks in combination with Capecitabine (Xeloda), 2 weeks on and 1 week off on a every 3 week cycle.

Docetaxel (taxotere) 35mg/m² IV over 60 min days 1, 8, and 15 in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.

CPT-11 (Irinotecan, Camptosar) - Patients being treated with an enzyme inducing antiepileptic drug (EIAED) will receive 340 mg/m² IV; others will receive 125 mg/m² IV 90 min on days 1 and 15, in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.

Paclitaxel (Taxol)90 mg/m2 IV over 60-90 min days 1, 8, and 15, in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.

Vinorelbine Tartrate (Navelbine®) 25 mg/m² IV over 10 min days 1, 8 and 15 in combination with avastin 10 mg/kg IV on days 1 and 15 of a 28-day cycle.

Gemcitabine (difluorodeoxycytidine, dFdC) 1000 mg/m2 IV on days 1 and 8 in combination with avastin 15 mg/kg IV on day 1 of a 21-day treatment cycle.

Bevacizumab / Capecitabine

Bevacizumab / Docetaxel

Bevacizumab / CPT-11

Bevacizumab / Paclitaxel

Bevacizumab /Vinorelbine Tartrate

Bevacizumab / Gemcitabine

Total

Gender

Region of Enrollment

Primary endpoint has not been analysed secondary to slow and low accrual numbers.

Safety and Tolerability Will be Assessed According to Standard (CTCAE Version 3.0) Toxicity Reporting Criteria.

Due to slow accrual study was prematurely closed and endpoint not analysed

Assess the Activity of Avastin When Added to Single Agent Chemotherapy, as Measured by Radiographic Response Rate,Progression Free Survival, and Overall Survival.

Determining the Safety and Tolerability of Adding Avastin to Single Agent Chemotherapy to Treat Patients With Brain Metastasis Originating From Breast Cancer

To Assess the Quality of Life During Treatment With This Therapeutic Approach

Bevacizumab / Irinotecan (Camptosar®, CPT-11)

Kimberly Blackwell, MD

Avastin (Bevacizumab)/ Capecitabine (Xeloda)

Avastin (Bevacizumab) / Camptosar (CPT 11/ Irinotecan)

Avastin (Bevacizumab)/Gemzar(Gemcitabine,Difluorodeoxycytidine

Avastin (Bevacizumab)/Navelbine (Vinorelbine Tartrate)

Breast Cancer

Bevacizumab(Avastin) 15 mg/kg every 3 weeks in combination with Capecitabine (Xeloda), 2 weeks on and 1 week off on a every 3 week cycle. until progression or unacceptable toxicity develops

Bevacizumab

Docetaxel 35mg/m² IV over 60 min days 1, 8, and 15 in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle. until progression or unacceptable toxicity develops

Docetaxel

CPT-11 (Irinotecan, Camptosar) - Patients being treated with an enzyme inducing antiepileptic drug (EIAED) will receive 340 mg/m² IV; others will receive 125 mg/m² IV 90 min on days 1 and 15, in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.until progression or unacceptable toxicity develops

CPT-11

Paclitaxel (Taxol)90 mg/m2 IV over 60-90 min days 1, 8, and 15, in combination with avastin 10 mg/kg on days 1 and 15 of a 28-day cycle.until progression or unacceptable toxicity develops

Paclitaxel

Vinorelbine Tartrate (Navelbine®) 25 mg/m² IV over 10 min days 1, 8 and 15 in combination with avastin 10 mg/kg IV on days 1 and 15 of a 28-day cycle. until progression or unacceptable toxicity develops

Vinorelbine Tartrate

Gemcitabine (difluorodeoxycytidine, dFdC) 1000 mg/m2 IV on days 1 and 8 in combination with avastin 15 mg/kg IV on day 1 of a 21-day treatment cycle.until progression or unacceptable toxicity develops

Gemcitabine

Palm Beach Cancer Center Institute

Presbyterian Health Care

Virginia Oncology Associates

A Phase II Safety and Tolerability Study of Bevacizumab When Added to Single-agent Chemotherapy to Treat Patient With Breast Cancer Metastatic to Brain

irinotecan/edema

Phase I/II Study of Pazopanib+ Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme

A Study of Gliadel Followed by Avastin + Irinotecan for Glioblastoma Multiforme (GBM)

A Phase II Safety and Tolerability Study of Bevacizumab When Added to Single-agent Chemotherapy to Treat Patient With Breast Cancer Metastatic to Brain

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