Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Glioblastoma

Brain Neoplasms

Gliosarcoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Brain Tumor, Adult

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Ramucirumab

Olaratumab

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive ramucirumab IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Patients receive olaratumab IV over 60-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

olaratumab

ramucirumab

Jaishri O. Blakeley, MD

RATIONALE: Monoclonal antibodies, such as ramucirumab and anti-PDGFR alpha monoclonal antibody IMC-3G3 (Olaratumab), can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.

PURPOSE: This phase II trial is studying how well ramucirumab or anti-PDGFR alpha monoclonal antibody IMC-3G3 works in treating patients with recurrent glioblastoma multiforme.

OBJECTIVES:

Primary

* To assess the progression-free survival rate at 6 months after treatment with ramucirumab or anti-PDGFR alpha monoclonal antibody IMC-3G3 in patients with recurrent glioblastoma multiforme.

Secondary

* To evaluate the acute and late toxicities associated with these regimens.
* To assess the objective tumor response rate.
* To estimate the overall survival of these patients.
* To describe the pharmacokinetic and pharmacodynamic profiles and immunogenicity of these regimens.

OUTLINE: This is a multicenter study. Patients are sequentially assigned to 1 of 2 treatment groups.

* Group 1: Patients receive ramucirumab IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
* Group 2: Patients receive anti-PDGFR alpha monoclonal antibody IMC-3G3 IV over 60-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Ramucirumab or Anti-PDGFR Alpha Monoclonal Antibody IMC-3G3 in Treating Patients With Recurrent Glioblastoma Multiforme

An Open Label, Phase 2 Study Evaluating the Safety and Efficacy of IMC-3G3 or IMC-1121B in Patients With Recurrent Glioblastoma Multiforme

PFS was defined as the start of treatment to the earliest date of tumor progression or death from any cause based on the modified Response Assessment in Neuro-Oncology Group through the American Society of Clinical Oncology (RANO) criteria. Progression is defined by any of the following: ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions; any new lesion; or clinical deterioration. RANO is a standardized response criteria using bi-dimensional measurements of the largest contrast-enhancing area (Macdonald, 1990).

The number of participants who experienced serious adverse events (SAEs) that were considered to be related to ramucirumab or olaratumab. A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.

The pts achievement of both measurement and confirmation criteria for a status of CR, PR or MR based on the modified RANO criteria.CR requires all of the following:complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks (wks);no new lesions;no corticosteroids;and stable or improved clinically.PR requires all of the following:≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions sustained for at least 4 wks;no new lesions;stable or reduced corticosteroid dose;and stable or improved clinically.MR requires ≥ 25% reduction in sum of products of the perpendicular diameters of all measureable enhancing lesions sustained for at least 4 wks and no new lesions or progression of non-measurable lesions. PD is defined by any of these: ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions;any new lesion;or clinical deterioration.

OS is the time from the start of treatment to the date of death. Participants who had not expired by the data analysis cutoff date were censored at their last date known to be alive.

Percentage of Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.

Percentage of Participants with Treatment Emergent (TE) anti-ramucirumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.

National Cancer Institute (NCI)

Eli Lilly and Company

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participants receive ramucirumab IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Group 1 Ramucirumab

Participants receive olaratumab IV over 60-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Group 2 Olaratumab

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Jaishri Blakely

Participants receive ramucirumab intravenously (IV) over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

All enrolled participants who received at least one dose of study drug.

Percentage of Participants Who Achieved Progression-Free Survival Rate at 6 Months (PFS-6)

Other adverse events (AEs)

Number of Participants With Treatment Emergent Adverse Events as Assessed by NCI CTCAE v4.0 (National Cancer Institute-Common Terminology Criteria for Adverse Events)

Percentage of Participants (Pts) With Complete Response (CR), Partial Response (PR) and Minor Response (MR) (Objective Response Rate [ORR])

All enrolled participants who received at least one dose of study drug. Participants censored in ramucirumab = 4 and olaratumab = 4.

Median Overall Survival (OS)

Cmin (n=5)

Cmax (n=6)

All enrolled participants who received at least one dose of ramucirumab and had evaluable PK data.

Pharmacokinetics (PK): Concentration Maximum (Cmax) and Concentration Minimum (Cmin) of Ramucirumab

Cmax (n=5)

All enrolled participants who received at least one dose of Olaratumab and had evaluable PK data.

PK: Cmax and Cmin of Olaratumab

Zero participants were analyzed for pharmacodynamic profile as the plasma collection procedure in this study was not fit for this purpose.

Pharmacodynamics (PD) Profiles

All enrolled participant who had any amount of olaratumab and evaluable anti-olaratumab antibody data.

Percentage of Participants With Anti-Olaratumab Antibodies (ADA)

All enrolled participants who had any amount of ramucirumab and evaluable anti-ramucirumab antibodies.

Percentage of Participants With Anti-Ramucirumab Antibodies (ADA)

Overall Study

Disease Attributes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Carmustine

O(6)-benzylguanine

Antineoplastic Agents, Alkylating

Alkylating Agents

Enzyme Inhibitors

Gliadel wafers in combination with O6-benzylguanine

Jennifer A. Quinn, MD

RATIONALE: Drugs used in chemotherapy, such as Gliadel wafer and O6-benzylguanine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving Gliadel wafer together with O6-benzylguanine works in treating patients with recurrent glioblastoma multiforme.

OBJECTIVES:

* Define the activity of Gliadel® wafers in combination with a 5-day infusion of O6-benzylguanine in patients with recurrent glioblastoma multiforme.
* Define the toxicity of Gliadel® wafers in combination with 5-day infusion of O6-benzylguanine in patients with recurrent glioblastoma multiforme.

OUTLINE: This is an open-label study.

Patients undergo surgical resection of tumor followed by placement of Gliadel® wafers . Within 6 hours after completion of surgery, patients receive a 1 hour high dose infusion of O6-benzylguanine followed by a lower dose continuous infusion for 5 days. Every 48 hours a repeat infusion of the high dose over 1 hour will be administered for a total of 3 doses.

After completion of study treatment, patients are followed every 8 weeks.

PROJECTED ACCRUAL: A total of 50 patients should be accrued for this study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ramucirumab or Anti-PDGFR Alpha Monoclonal Antibody IMC-3G3 in Treating Patients With Recurrent Glioblastoma Multiforme	NCT00895180	Adult Glioblast...	olaratumab ramucirumab	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Ramucirumab or Anti-PDGFR Alpha Monoclonal Antibody IMC-3G3 in Treating Patients With Recurrent Glioblastoma Multiforme	NCT00895180	Adult Glioblast...	olaratumab ramucirumab	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Gliadel Wafer and O6-Benzylguanine in Treating Patients With Recurrent Glioblastoma Multiforme	NCT00362921	Recurrent Adult...	Gliadel wafers ...	18 Years -	Duke University

Spots Global Cancer Trial Database for adult glioblastoma multiforme