Neoplasms

All Conditions

Rare Diseases

Glioma

Glioblastoma

Gliosarcoma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Irinotecan

Carmustine

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Gliadel/Avastin/CPT-11

Annick Desjardins, MD, FRCPC

The primary objective of the study is to use 24 week survival to assess the efficacy of the combination of Gliadel followed by Avastin and irinotecan in the treatment of grade IV malignant glioma patients following surgical resection. The secondary objectives are to determine the progression-free survival following the combination of Gliadel followed by Avastin and irinotecan and to describe the toxicity of Gliadel followed by Avastin and irinotecan.

This is a phase II study of the combination of Gliadel followed by Avastin and irinotecan in grade IV malignant glioma patients. The study will have survival and toxicity endpoints. Subjects will be identified by the investigator as those patients who have histologically documented grade IV malignant glioma (glioblastoma multiforme or gliosarcoma) with recurrent or progressive disease who are able to undergo a gross total resection (GTR).

Part I: Gliadel wafer- 1-8 wafers inserted at time of gross total resection. Treatment cycle is 42 days in length. For patients with ≥ Grade 1 toxicity will allow 84 days prior to beginning therapy with Avastin and Irinotecan (CPT-11).

Part II: Avastin Plus Irinotecan (Cycles 1-12) consists of the following (cycle length is 6 weeks):

* Irinotecan 125 mg/m2 (not taking enzyme-inducing anti-epileptic drugs (EIAEDs)) or 340 mg/m2 (taking EIAEDs) given every two weeks on days 1, 15, 29, etc.;
* 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 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, etc.

The primary objective of this phase II study is to determine whether the administration of Gliadel wafers followed by Avastin and irinotecan to patients with recurrent GBM is a treatment regimen worthy of further investigation in a randomized clinical trial. The basis for making this decision will be the proportion of patients who survive at least 24 weeks after initiation of protocol treatment.

In the initial Phase I and II clinical trials, four potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, and hemorrhage. The two major toxicities associated with irinotecan are myelosuppression and diarrhea. Side effects associated with Gliadel are seizures, brain edema (swelling), healing abnormalities, wound infection and body pain.

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

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

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.

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.

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.

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

Eisai Inc.

Genentech, Inc.

Duke University

Adverse Events were collected for the study using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, but were converted to CTCAE version 4.0 for entry in ClinicalTrials.gov.

Age Continuous

Sex: Female, Male

24-week Overall Survival

24-week Progression-free Survival (PFS)

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)

Median Overall Survival (OS)

Grade 5 CNS Hemorrhage

Grade 4 CNS Hemorrhage

Incidence and Severity of Central Nervous System (CNS) Hemorrhage

Grade >= 4 Hematologic Toxicity

Grade >= 3 Non-hematologic Toxicity

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

Symptoms and General Pathology

Nervous System Diseases

Recurrence

Brain Neoplasms

Antineoplastic Agents, Alkylating

Alkylating Agents

IL13-PE38QQR

surgery and catheter placement (2 procedures)

prolifespan 20 with carmustine implant (GLIADEL® Wafer)

surgery and wafer placement (1 procedure)

The purpose of the PRECISE trial is to determine whether overall survival duration, safety, and quality of life are improved for patients treated with IL13-PE38QQR compared to patients treated with GLIADEL® Wafer following surgical tumor removal in the treatment of first recurrence of glioblastoma multiforme.

PRECISE is a Phase III clinical trial of experimental drug IL13-PE38QQR (Study Drug). IL13-PE38QQR is a tumor-targeting agent administered by a continuous infusion directly into the brain around the cavity where the tumor has been removed. Through previous research, this Study Drug has shown potential to control some of the recurrent malignant gliomas, such as glioblastoma multiforme (GBM), anaplastic astrocytoma, and malignant mixed oligoastrocytoma.

The Study Drug is made by combining a human protein (IL13) with a portion of a bacterial toxin protein, Pseudomonas Exotoxin (PE). The IL13 portion binds to receptors on the tumor like a "key to a lock," allowing the PE portion to enter and kill those cells. Since tumor cells preferentially bind the drug, normal (healthy) brain cells are much less likely to be damaged by the drug. The Study Drug is delivered through tubing or catheters placed directly into the area surrounding the resection cavity. These catheters will be surgically placed from 2-7 days after the tumor has been removed. A pump is then used to slowly push the drug solution through the catheters using convection-enhanced delivery (CED) over a period of 4 days.

The GLIADEL® Wafer is an anti-cancer drug that is approved by the U.S. Food and Drug Administration (FDA) and sold for the treatment of recurrent or newly diagnosed GBM. Patients receiving GLIADEL® will have wafers placed at the time of surgery to remove tumor.

Eligible patients enrolled in the PRECISE trial will be randomly assigned to receive either IL13-PE38QQR or GLIADEL® Wafer. Patients will have a 2 out of 3 chance to receive IL13-PE38QQR and 1 out of 3 chance to receive GLIADEL® Wafer.

The PRECISE Trial: Study of IL13-PE38QQR Compared to GLIADEL Wafer in Patients With Recurrent Glioblastoma Multiforme

PRECISE - Phase III Randomized Evaluation of Convection Enhanced Delivery of IL13-PE38QQR Compared to GLIADEL® Wafer With Survival Endpoint in Glioblastoma Multiforme Patients at First Recurrence

INSYS Therapeutics Inc

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Resect the tumor as completely as possible. After repeated irrigation of the decompressed area demonstrates no bleeding, and care is taken not to have any foreign material enter the ventricle, up to 8 GLIADEL wafers should be placed to cover the entire surface area of the resection cavity (if possible). Slight overlapping of wafer edges is permitted. The number of wafers will be determined by the size of the tumor resection cavity. Each GLIADEL wafer contains 7.7 mg of carmustine, resulting in a dose of 61.6 mg when 8 wafers are implanted. The GLIADEL wafer is a round white to yellow disk with flat surfaces.

GLIADEL

The purpose of this study is to determine the effect of the surgical intervention and insertion of GLIADEL wafers on the neurocognitive functioning in patients with metastatic brain cancer.

Exploratory Study, Evaluating the Treatment Effect of Surgery Plus GLIADEL® Wafer in Patients With Metastatic Brain Cancer

A Phase 2, Multicenter, Exploratory Study, Evaluating the Treatment Effect of Surgery Plus GLIADEL® Wafer in Patients With Metastatic Brain Cancer

NF was assessed as the performance of 3 neurocognitive domains:memory(MD),executive function(EFD), fine motor coordination(FMCD). For each domain, z-scores were derived from participant's scores in individual neurocognitive tests using an age-adjusted and education-adjusted normative distribution of scores from an unimpaired population.Individual z-scores from related tests were averaged to determine overall z-score.If a z-score average decreased from baseline by greater than or equal to(\>=)3 standard deviations(SD)in tests' normative age-adjusted distribution on 2 consecutive visits or decreased by \>=3 SD on last follow-up visit, participant were considered to have significant deterioration in their NF at time of the first decrease in z-score.Deterioration in NF:demonstrated deterioration for at least two of the three neurocognitive domains based on these changes from screening.Rate of deterioration in NF was measured as estimated percentage of participants using Kaplan-Meier method.

Preservation of NF was defined as a decrease of \<=1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).

Preservation of NF was defined as a decrease of less than or equal to (\<=) 1 SD, any increase, or no change (0 SD) in z-score for each domain (memory domain, executive function domain, and fine motor coordination domain).

The correlation between recurrence (local, distant or overall) \& NF was assessed by presenting change in NF domain scores (memory domain \[MD\], executive function domain \[EFD\], fine motor coordination domain \[FMCD\]) after tumor recurrence (Visits X, X+1, X+2, and X+3) compared to before tumor recurrence (Visit X-1). Here 'Visit X' refers to visit at which participants had tumor recurrence, Visit X-1 refers to visit immediately before the recurrence and X+1, X+2, X+3 refers to subsequent first, second \& third visit after the recurrence.NF domain z-scores were derived from participant's scores in individual neurocognitive tests using an age-adjusted \&education-adjusted normative distribution of scores from an unimpaired population. Individual z-scores from related tests were averaged to determine overall z-score for each of NF domains.

Neurologic Death was defined as death due to progression of neurologic disease.

The time to neurocognitive deterioration was defined as the number of days between the date of study treatment and the date of neurocognitive deterioration based on NF assessment. This was assessed using Kaplan Meier method.

Neurocognitive decline was defined as any decrease in NF scores less than (\<) 0 SD from baseline. Here, in category titles EFD represents Executive Function Domain and FMCD represents Fine Motor Coordination Domain.

The study team only has access to serious and all treatment-emergent adverse events (serious and non-serious). All efforts to locate other adverse event data have been exhausted. All treatment-emergent adverse events, whether serious or non-serious, have been reported in the Other (Not Including Serious) Adverse Events tables as severity of the event cannot be distinguished in available data.

Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine). Participants were followed up to 12 months or until the participant experienced local recurrence, withdrew, died, was lost to follow-up, or the study was closed.

Age, Continuous

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The safety analysis set included all enrolled participants who underwent surgical resection and received GLIADEL treatment.

Eisai Medical Services

Participants with metastatic brain tumors who underwent neurosurgical resection of their lesions were implanted with up to 8 GLIADEL wafers in their tumor cavities (each containing 7.7 mg of carmustine).

The per protocol 1 (PP1) population included all participants who received surgery plus GLIADEL, had an intra-operative diagnosis confirmed by permanent pathology findings, remained compliant with protocol procedures, and did not receive disallowed concomitant therapies (example whole brain radiation therapy \[WBRT\]) before recurrence.

Rate of Deterioration in Neurocognitive Functioning (NF) at Month 12

Domains preserved=3

Domains preserved=2

Domains preserved=1

Domains preserved=0

The PP1 population included all participants who received surgery plus GLIADEL, had an intra-operative diagnosis confirmed by permanent pathology findings, remained compliant with protocol procedures, and did not receive disallowed concomitant therapies (example WBRT) before recurrence.

Number of Participants With Neurocognitive Domains Preserved at Month 2

Number of Participants With Neurocognitive Domains Preserved at Month 4

Number of Participants With Neurocognitive Domains Preserved at Month 6

Number of Participants With Neurocognitive Domains Preserved at Month 9

Number of Participants With Neurocognitive Domains Preserved at Month 12

Local Recurrence

Distant Recurrence

Overall Recurrence

Percentage of Participants With Brain Tumor Recurrence (Local Recurrence, Distant Recurrence and Overall Recurrence)

Time to Local Recurrence

Time to Distant Recurrence

Time to Overall Recurrence

Time to Recurrence (Local, Distant and Overall)

PP1 population. Since only two participants had residual tumor mass, no correlation analyses were performed for recurrence and residual mass effect.

Correlation of Tumor Recurrence With Residual Mass Effect

Local Recurrence: MD at Visit (X-1)

Local Recurrence: MD Change at Visit (X-1)

Local Recurrence: MD Change at Visit (X+1)

Local Recurrence: MD Change at Visit (X+2)

Local Recurrence: MD Change at Visit (X+3)

Local Recurrence: EFD at Visit (X-1)

Local Recurrence: EFD Change at Visit (X-1)

Local Recurrence: EFD Change at Visit (X+1)

Local Recurrence: EFD Change at Visit (X+2)

Local Recurrence: EFD Change at Visit (X+3)

Local Recurrence: FMCD at Visit (X-1)

Local Recurrence: FMCD Change at Visit (X-1)

Local Recurrence: FMCD Change at Visit (X+1)

Local Recurrence: FMCD Change at Visit (X+2)

Local Recurrence: FMCD Change at Visit (X+3)

Distant Recurrence: MD at Visit (X-1)

Distant Recurrence: MD Change at Visit (X-1)

Distant Recurrence: MD Change at Visit (X+1)

Distant Recurrence: MD Change at Visit (X+2)

Distant Recurrence: MD Change at Visit (X+3)

Distant Recurrence: EFD at Visit (X-1)

Distant Recurrence: EFD Change at Visit (X-1)

Distant Recurrence: EFD Change at Visit (X+1)

Distant Recurrence: EFD Change at Visit (X+2)

Distant Recurrence: EFD Change at Visit (X+3)

Distant Recurrence: FMCD at Visit (X-1)

Distant Recurrence: FMCD Change at Visit (X-1)

Distant Recurrence: FMCD Change at Visit (X+1)

Distant Recurrence: FMCD Change at Visit (X+2)

Distant Recurrence: FMCD Change at Visit (X+3)

Overall Recurrence: MD at Visit (X-1)

Overall Recurrence: MD Change at Visit (X-1)

Overall Recurrence: MD Change at Visit (X+1)

Overall Recurrence: MD Change at Visit (X+2)

Overall Recurrence: MD Change at Visit (X+3)

Overall Recurrence: EFD at Visit (X-1)

Overall Recurrence: EFD Change at Visit (X-1)

Overall Recurrence: EFD Change at Visit (X+1)

Overall Recurrence: EFD Change at Visit (X+2)

Overall Recurrence: EFD Change at Visit (X+3)

Overall Recurrence: FMCD at Visit (X-1)

Overall Recurrence: FMCD Change at Visit (X-1)

Overall Recurrence: FMCD Change at Visit (X+1)

Overall Recurrence: FMCD Change at Visit (X+2)

Overall Recurrence: FMCD Change at Visit (X+3)

Correlation of Tumor Recurrence (Local, Distant or Overall) With NF Domain Scores

Percentage of Participants With Neurologic Death

Time to Neurocognitive Deterioration

Month 2: Memory Domain, decline <0 to -1 SD

Month 2: Memory Domain, decline <-1 to -2 SD

Month 2: Memory Domain, decline <-2 to -3 SD

Month 2: Memory Domain, decline <-3 to -4 SD

Month 2: Memory Domain, decline <-4 to -5 SD

Month 2: Memory Domain, decline <-5 SD

Month 2: EFD, decline <0 to -1 SD

Month 2: EFD, decline <-1 to -2 SD

Month 2: EFD, decline <-2 to -3 SD

Month 2: EFD, decline <-3 to -4 SD

Month 2: EFD, decline <-4 to -5 SD

Month 2: EFD, decline <-5 SD

Month 2: FMCD, decline <0 to -1 SD

Month 2: FMCD, decline <-1 to -2 SD

Month 2: FMCD, decline <-2 to -3 SD

Month 2: FMCD, decline <-3 to -4 SD

Month 2: FMCD, decline <-4 to -5 SD

Month 2: FMCD, decline <-5 SD

Month 4: Memory Domain, decline <0 to -1 SD

Month 4: Memory Domain, decline <-1 to -2 SD

Month 4: Memory Domain, decline <-2 to -3 SD

Month 4: Memory Domain, decline <-3 to -4 SD

Month 4: Memory Domain, decline <-4 to -5 SD

Month 4: Memory Domain, decline <-5 SD

Month 4: EFD, decline <0 to -1 SD

Month 4: EFD, decline <-1 to -2 SD

Month 4: EFD, decline <-2 to -3 SD

Month 4: EFD, decline <-3 to -4 SD

Month 4: EFD, decline <-4 to -5 SD

Month 4: EFD, decline <-5 SD

Month 4: FMCD, decline <0 to -1 SD

Month 4: FMCD, decline <-1 to -2 SD

Month 4: FMCD, decline <-2 to -3 SD

Month 4: FMCD, decline <-3 to -4 SD

Month 4: FMCD, decline <-4 to -5 SD

Month 4: FMCD, decline <-5 SD

Month 6: Memory Domain, decline <0 to -1 SD

Percentage of Participants With Neurocognitive Decline in NF by Severity (Memory Domain, Executive Function Domain, and Fine Motor Coordination Domain)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Gliadel Followed by Avastin + Irinotecan for Glioblastoma Multiforme (GBM)	NCT00735436	Malignant Gliom... Glioblastoma Mu... Gliosarcoma	Gliadel/Avastin...	18 Years -	Duke University
The PRECISE Trial: Study of IL13-PE38QQR Compared to GLIADEL Wafer in Patients With Recurrent Glioblastoma Multiforme	NCT00076986	Glioblastoma Mu...	IL13-PE38QQR surgery and cat... prolifespan 20 ... surgery and waf...	18 Years -	INSYS Therapeutics Inc
Exploratory Study, Evaluating the Treatment Effect of Surgery Plus GLIADEL® Wafer in Patients With Metastatic Brain Cancer	NCT00525590	Metastatic Brai...	GLIADEL	18 Years -	Eisai Inc.
The PRECISE Trial: Study of IL13-PE38QQR Compared to GLIADEL Wafer in Patients With Recurrent Glioblastoma Multiforme	NCT00076986	Glioblastoma Mu...	IL13-PE38QQR surgery and cat... prolifespan 20 ... surgery and waf...	18 Years -	INSYS Therapeutics Inc
Gliadel, XRT, Temodar, Avastin Followed by Avastin, Temodar for Newly Diagnosed Glioblastoma Multiforme (GBM)	NCT01186406	Glioblastoma Mu... Gliosarcoma	Gliadel Radiation Thera... Avastin Temodar	18 Years -	Duke University
A Study of Gliadel Followed by Avastin + Irinotecan for Glioblastoma Multiforme (GBM)	NCT00735436	Malignant Gliom... Glioblastoma Mu... Gliosarcoma	Gliadel/Avastin...	18 Years -	Duke University
Gliadel, XRT, Temodar, Avastin Followed by Avastin, Temodar for Newly Diagnosed Glioblastoma Multiforme (GBM)	NCT01186406	Glioblastoma Mu... Gliosarcoma	Gliadel Radiation Thera... Avastin Temodar	18 Years -	Duke University
Examination of Changes on Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) in Patients Who Receive Gliadel Wafers During Initial Surgery for Glioblastoma Multiforme. Response or Failure to Gliadel Wafers for Subjects With Glioblastoma Multiforme.	NCT00645385	Glioblastoma Mu... Anaplastic Astr... Anaplastic Olig...	MRS Spectroscop...	18 Years - 85 Years	Weill Medical College of Cornell University

Spots Global Cancer Trial Database for gliadel

Every month we try and update this database with for gliadel cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for gliadel

Every month we try and update this database with for gliadel cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for gliadel cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.