Astrocytoma, Grades II, III and IV

Glioblastoma Multiforme

Giant Cell Glioblastoma

Glioma

Oligodendrogliomas

LB-100 will be infused over 2 hours via syringe pump in the OR or 1-12 hours before to surgery. The dose established from a Phase I study will be 2.33 mg/m(2).

LB-100

National Institutes of Health Clinical Center

Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma

Phase II Trial of LBlOO, a Protein Phosphatase 2A Inhibitor, in Recurrent Gliomas

To determine the pharmacokinetic properties of LB100 in Gliomas tumor tissues

determine the plasma concentration and calculated PK parameters of LB100 and LB100M (endothall).

determine the concentration LB100 and its major metabolite, 7-oxabicyclo [2.2.1] heptanes-2,3- dicarboxylic acid (LB100M) in glioma tumor tissue when a known non-toxic dose of LB100 is delivered intravenously over 2 hours

Intra-patient PD effect in PBMC and tumor tissue will be evaluated in all subjects for presence of correlation to identify potential predictive markers

determine changes in phospho- protein expression in circulating PBMC

National Cancer Institute (NCI)

Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II.

Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II.
cetuximab: Given IV
irinotecan hydrochloride: Given IV

Arm I (Cetuximab, Irinotecan Hydrochloride)

Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
cetuximab: Given IV
irinotecan hydrochloride: Given IV
vemurafenib: Given PO

Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib)

Total

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Prior treatment with Irinotecan

From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. Progression is defined as one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of any new lesion/site; and/or death due to disease without prior documentation of progression and without symptomatic deterioration.

Progression-free Survival

Only adverse events that are possibly, probably or definitely related to study drug are reported.

Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cetuximab + Irinotecan

Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Vemurafenib + Cetuximab + Irinotecan

Crossover: Vemurafenib + Cetuximab + Irinotecan

Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug

From date of randomization to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Overall Survival

Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.

Overall Response Rate

From date of Step 3 Crossover registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of progression are censored at date of last contact. Progression is defined as one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of any new lesion/site; and/or death due to disease without prior documentation of progression and without symptomatic deterioration.

Progression-free Survival in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1

Overall Survival in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1

Overall Response Rate in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1

Overall Study

SWOG Statistician

Colorectal Cancer

cetuximab

irinotecan hydrochloride

vemurafenib

Anchorage Radiation Therapy Center

Alaska Breast Care and Surgery LLC

Alaska Oncology and Hematology LLC

Alaska Regional Hospital

Alaska Women's Cancer Care

Anchorage Oncology Centre

Katmai Oncology Group

Providence Alaska Medical Center

Fairbanks Memorial Hospital

University of Arizona Cancer Center-Orange Grove Campus

University of Arizona Cancer Center-North Campus

The University of Arizona Medical Center-University Campus

Mercy Cancer Center-Hot Springs

Fowler Family Center for Cancer Care

University of Arkansas for Medical Sciences

Veteran's Administration Medical Center

Kaiser Permanente-Anaheim

Kaiser Permanente-Deer Valley Medical Center

Sutter Auburn Faith Hospital

Sutter Cancer Centers Radiation Oncology Services-Auburn

Kaiser Permanente-Baldwin Park

Kaiser Permanente-Bellflower

Alta Bates Summit Medical Center-Herrick Campus

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Mills - Peninsula Hospitals

Sutter Cancer Centers Radiation Oncology Services-Cameron Park

Eden Hospital Medical Center

Sutter Davis Hospital

City of Hope Comprehensive Cancer Center

Epic Care-Dublin

Bay Area Breast Surgeons Inc

Epic Care Partners in Cancer Care

Kaiser Permanente Hospital

Kaiser Permanente-Fremont

Kaiser Permanente

Marin Cancer Care Inc

Marin General Hospital

Kaiser Permanente - Harbor City

Kaiser Permanente-Irvine

Kaiser Permanente Los Angeles Medical Center

Los Angeles County-USC Medical Center

USC / Norris Comprehensive Cancer Center

Kaiser Permanente-Cadillac

Contra Costa Regional Medical Center

Fremont - Rideout Cancer Center

Memorial Medical Center

Kaiser Permanente-Modesto

Palo Alto Medical Foundation-Camino Division

Palo Alto Medical Foundation-Gynecologic Oncology

Sutter Cancer Research Consortium

Alta Bates Summit Medical Center - Summit Campus

Bay Area Tumor Institute

Hematology and Oncology Associates-Oakland

Kaiser Permanente Oakland-Broadway

Kaiser Permanente-Oakland

UC Irvine Health/Chao Family Comprehensive Cancer Center

Palo Alto Medical Foundation Health Care

Kaiser Permanente - Panorama City

Keck Medical Center of USC Pasadena

PCR Oncology

Kaiser Permanente-Rancho Cordova Cancer Center

Kaiser Permanente-Redwood City

Kaiser Permanente-Richmond

Kaiser Permanente-Riverside

Rohnert Park Cancer Center

Kaiser Permanente-Roseville

Sutter Cancer Centers Radiation Oncology Services-Roseville

Sutter Roseville Medical Center

The Permanente Medical Group-Roseville Radiation Oncology

Sutter General Hospital

University of California Davis Comprehensive Cancer Center

Kaiser Permanente-South Sacramento

South Sacramento Cancer Center

Kaiser Permanente - Sacramento

Salinas Valley Memorial

Kaiser Permanente-San Diego Mission

Kaiser Permanente-San Diego Zion

California Pacific Medical Center-Pacific Campus

Kaiser Permanente-San Francisco

UCSF Medical Center-Mount Zion

UCSF Medical Center-Mission Bay

Kaiser Permanente-Santa Teresa-San Jose

Kaiser Permanente San Leandro

Kaiser Permanente-San Marcos

Kaiser Permanente-San Rafael

Kaiser Permanente Medical Center - Santa Clara

Palo Alto Medical Foundation-Santa Cruz

Kaiser Permanente-Santa Rosa

Sutter Pacific Medical Foundation

Kaiser Permanente Cancer Treatment Center

Kaiser Permanente-South San Francisco

Kaiser Permanente-Stockton

Palo Alto Medical Foundation-Sunnyvale

Gene Upshaw Memorial Tahoe Forest Cancer Center

Sutter Cancer Centers Radiation Oncology Services-Vacaville

Kaiser Permanente Medical Center-Vacaville

Kaiser Permanente-Vallejo

Sutter Solano Medical Center/Cancer Center

Kaiser Permanente-Walnut Creek

S1406 Phase II Study of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF Mutant Metastatic Colorectal Cancer

Randomized Phase II Study of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF Mutant Metastatic Colorectal Cancer

Southwest Oncology Group

Roche-Genentech

Beginning preferably between day 56 and day 85 post-ASCT, but may be delayed up to day 200, patients receive isotretinoin PO BID for 14 days. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients may cross over to Arm II provided they have not experienced disease progression and have not received any further anti-neuroblastoma therapy following completion of isotretinoin therapy.

Beginning preferably between day 56 and day 85 post-ASCT, but may be delayed up to day 200, patients receive immunotherapy comprising sargramostim SC or IV over 2 hours on days 0-13 during courses 1, 3, and 5 and dinutuximab IV over 10-20 hours on days 3-6 of courses 1-5. Patients also receive aldesleukin IV continuously on days 0-3 and 7-10 during courses 2 and 4. Immunotherapy repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity. Patients also receive isotretinoin as in Arm I beginning on day 11 of immunotherapy.

Regimen A

Regimen B

Region of Enrollment

Comparison to determine if RA + Immunotherapy improves EFS as compared to RA Only

Randomized to Regimen B - RA + Immunotherapy

Event-Free Survival (EFS)

Comparison to determine if RA + Immunotherapy improves EFS as compared to RA Only for the subgroup of randomized patients with INSS Stage 4 disease. Descriptive comparison of outcome data for patients with persistent disease documented by biopsy to historical data for the analogous patients from CCG-3981.

EFS for patients receiving RA + Immunotherapy following the cessation of the randomized portion of the study.

Non-randomly assigned to Regimen B after halting of randomization, excluding patients with persistent disease

Event-Free Survival (EFS) of Patients From the Non-randomized Portion of the Trial

Proportion of patients experiencing at least one Grade 3 or higher toxicity.

Patients that received RA + Immunotherapy before halting of randomization

Incidence of Toxicities Assessed Using Common Terminology Criteria for Adverse Events Version 4.0

Number of courses of therapy delivered for patients randomized to RA + Immunotherapy vs. patients non-randomly assigned to RA + Immunotherapy, excluding patients with persistent disease.

Number of Courses of Therapy Delivered

Comparison to determine if RA + Immunotherapy improves OS as compared to RA Only. Comparison to determine if RA + Immunotherapy improves OS as compared to RA only and for the subgroup of randomized patients with INSS Stage 4 disease.

Overall Survival (OS)

OS for patients receiving RA + Immunotherapy following the cessation of the randomized portion of the study.

Overall Survival (OS) of Patients From the Non-randomized Portion of the Trial

The average level of HACA at each collection time point during immunotherapy will be calculated.

Average Level of HACA

In general, descriptive summaries will include n, mean, standard deviation, median, minimum, maximum and 90% confidence intervals for continuous variables, and n and percent for categorical variables. Summaries will present data by assessment time when appropriate.

Cardiac Repolarization

A descriptive analysis of the change from baseline of MRD will be performed. Also, a Wilcoxon rank-sum test will be performed to compare the median change from baseline of MRD between the two treatment arms. A multivariate Cox proportional hazards regression model will test to see if the change in MRD burden is associated with EFS or OS.

Change in MRD

A multivariate Cox proportional hazards regression model will test to see if the dinutuximab serum level, HACA titer, effector cell function, or serum marker for effector cell activation are associated with EFS or OS.

Change in Tumor Biology

Kaplan-Meier plots of EFS and OS will be generated after dichotomization using the median value for the cohort. To determine the prognostic value of circulating B7-H6 level, univariate analysis will be performed using a log rank test for EFS and OS. In multivariable analysis of EFS and OS, Cox models will be used to test for the independent prognostic ability of circulating B7-H6 level, adjusting for significant prognostic factors including MYCN status, INSS stage, histology and age at diagnosis.

Circulating B7-H6 Levels

Kaplan-Meier plots of EFS will be generated for the three genotype subgroups of FcR as well as for the three genotype subgroups of Kir/Kir-ligand. In addition, a log rank test comparison will be made in a pairwise fashion of each of the genotypes within FcR and within Kir/Kir-ligand.

Genotype of FcR

Genotype of Kir/Kir-ligand

To determine if there is a relationship of the peak serum concentration level with EFS, the term for this level will be tested in a Cox proportional hazards model. To determine if there is a relationship of the peak serum concentration level with toxicity rates, Kendall's Tau statistic will be calculated.

Isotretinoin Pharmacokinetic Parameters

Levels of ADCC

Kaplan-Meier plots of EFS and OS will be generated after dichotomization using the median value for the cohort. To determine the prognostic value of NKp30 isoform expression and SNP, univariate analysis will be performed using a log rank test for EFS and OS. In multivariable analysis of EFS and OS, Cox models will be used to test for the independent prognostic ability of NKp30 isoform expression and SNP, adjusting for significant prognostic factors including v-MYC myelocytomatosis viral related oncogene, neuroblastoma derived (avian) (MYCN) status, INSS stage, histology and age at diagnosis.

NKp30 Isoform Expression and SNP

A Fisher's exact test will be performed to determine if the presence of naturally occurring anti-glycan antibodies correlates with allergic reactions. A Wilcoxon test will be performed to determine if the presence of naturally occurring anti-glycan antibodies correlates with blood levels of dinutuximab.

Presence of Naturally Occurring Anti-glycan Antibodies

Results Reporting Coordinator

Localized Resectable Neuroblastoma

Localized Unresectable Neuroblastoma

Recurrent Neuroblastoma

Regional Neuroblastoma

Stage 4 Neuroblastoma

Stage 4S Neuroblastoma

Isotretinoin With or Without Dinutuximab, Aldesleukin, and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma

Phase III Randomized Study of Chimeric Antibody 14.18 (Ch14.18) in High Risk Neuroblastoma Following Myeloablative Therapy and Autologous Stem Cell Rescue

neuroblastoma/phosphatase

Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma

S1406 Phase II Study of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF Mutant Metastatic Colorectal Cancer

Isotretinoin With or Without Dinutuximab, Aldesleukin, and Sargramostim Following Stem Cell Transplant in Treating Patients With Neuroblastoma

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