Phase II study of combination carboplatin and erlotinib in patients with recurrent glioblastoma multiforme

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2024-2024 ◽  
Author(s):  
J. F. De Groot ◽  
M. R. Gilbert ◽  
K. R. Hess ◽  
T. Hanna ◽  
M. Groves ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Tumor Tissue ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Credible Interval ◽  
Recurrent Glioblastoma ◽  
Clinical Activity ◽  
Recurrent Glioblastoma Multiforme

2024 Background: Targeting the epidermal growth factor receptor (EGFR) in glioblastoma is effective in a subset of patients whose tumors express the phosphatase and tensin homolog (PTEN) tumor suppressor gene and overexpress the EGF variant vIII receptor. Therefore, this study was designed to assess the clinical activity of the EGFR inhibitor erlotinib when combined with carboplatin and to determine molecular predictors of response. The primary endpoint is progression-free survival (PFS). To be eligible for the study, patients had to have recurrent, histologically confirmed glioblastoma or gliosarcoma, no more than two prior relapses, a KPS = 60, and no enzyme-inducing anticonvulsants. Methods: In this ongoing phase II study, patients are given carboplatin intravenously on day 1 of every 28-day cycle to achieve a target AUC of 6 (mg x ml/min) based on creatinine clearance. Erlotinib is administered orally once daily throughout the 28-day cycle at 150 mg/day with dose escalation to 200 mg/day, as tolerated. Patients undergo clinical and MRI assessment every 4 weeks. The primary endpoint is median PFS using a Bayesian time-to-event design. To determine histologic correlates of response, tumor tissue is undergoing immunohistochemical evaluation for known markers of response to EGFR inhibitors, including PI3K/AKT and PTEN status. Results: Of the first 20 patients enrolled, 17 were evaluable and all had failed temozolomide-based therapy. The median age is 56 years, and the median KPS is 80. The median time to progression is 15.2 weeks with a 95% credible interval of 8.0 to 28.4 weeks. These results compare favorably with historical data (median of 9.0 weeks, 95% CI of 8.1 to 10.1 weeks). Bayesian analysis using computer-based simulations indicate a high probability (69%) that the median PFS in our study is at least 3 weeks longer than the historical median PFS. Grade 3 and 4 toxicities included fatigue, leukopenia, thrombocytopenia and rash requiring dose reductions. Conclusions: The results from this ongoing study suggest that the combination of carboplatin and erlotinib has promising activity in patients with recurrent glioblastoma who have failed temozolomide-based therapy. Tumor tissue is being analyzed to determine molecular markers of response. [Table: see text]

A stratified phase II study of cetuximab for the treatment of recurrent glioblastoma multiforme: Preliminary results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 1558-1558 ◽  
Author(s):  
J. Sadones ◽  
C. Chaskis ◽  
E. J. Joosens ◽  
L. A. Dhondt ◽  
J. Baurain ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Gene Copy Number ◽  
Growth Factor Receptor ◽  
Recurrent Glioblastoma ◽  
Gene Copy ◽  
Recurrent Glioblastoma Multiforme ◽  
Egfr Gene ◽  
Recurrent Gbm

1558 Background: The Epidermal Growth Factor Receptor (EGFR) gene is frequently amplified and mutated in high-grade gliomas. We are investigating the activity of the EGFR-targeted monoclonal antibody cetuximab for the treatment of patients (pts) with recurrent glioblastoma multiforme (GBM) following surgery, radiotherapy and chemotherapy. Methods: Adult pts with recurrent GBM are allocated to two parallel treatment strata according to the amplification status of the EGFR gene (determined by FISH). According to a Simon two-stage phase II study design 1 response in 13 pts/stratum is required to continue recruitment and complete the second stage of pt recruitment. Cetuximab is administered at 400 mg/m2 (2 hour infusion) day 1 and 250 mg/m2 day 8 and for all subsequent weekly doses (1 hour infusion). Results: Between May and December 2005, 17 pts were recruited (10 without EGFR-ampl, 4 with EGFR-ampl and 3 under investigation); 4F/13M; median age 51 years, range 32–67). Recruitment is ongoing. Sixteen pts initiated study treatment; 1 pt withdrew consent before the initiation of therapy. Treatment related toxicity in the first 94 treatment cycles consisted of grade 1/2 folliculitis/dermitis in all treated pts. Grade 3 adverse events consisted of thrombocytopenia (n=1 pt), diminished consciousness (n=1 pt), dizziness/confusion (n=1 pt), infectious bronchopneumonia (n=1 pt), and infectious cellulitis (n=1 pt). Thirteen pts have been evaluated for response ≤ week 8 of study treatment. Eleven pts had progression of disease. Two patients had SD at 8 weeks (follow-up is ongoing). Conclusions: These preliminary data suggest that cetuximab can be safely administered to pretreated patients with recurrent GBM. Updated results regarding safety and activity as well as a correlative study of EGFR and PTEN expression and gene copy number of the GBM and response to cetuximab will be presented at the meeting. No significant financial relationships to disclose.

Phase II Study of Imatinib Mesylate Plus Hydroxyurea in Adults With Recurrent Glioblastoma Multiforme

2005 ◽  
Vol 23 (36) ◽  
pp. 9359-9368 ◽  
Author(s):  
David A. Reardon ◽  
Merrill J. Egorin ◽  
Jennifer A. Quinn ◽  
Jeremy N. Rich ◽  
Idharan Gururangan ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Imatinib Mesylate ◽  
Phase Ii ◽  
Cox Regression ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Cox Regression Analysis

Purpose We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). Patients and Methods Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). Results Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. Conclusion Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.

Randomized Phase II Study of Cilengitide, an Integrin-Targeting Arginine-Glycine-Aspartic Acid Peptide, in Recurrent Glioblastoma Multiforme

2008 ◽  
Vol 26 (34) ◽  
pp. 5610-5617 ◽  
Author(s):  
David A. Reardon ◽  
Karen L. Fink ◽  
Tom Mikkelsen ◽  
Timothy F. Cloughesy ◽  
Alison O'Neill ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Antitumor Activity ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Wide Range ◽  
First Recurrence ◽  
Arginine Glycine Aspartic Acid

PurposeCilengitide, an inhibitor of αvβ3 and αvβ5 integrin receptors, demonstrated minimal toxicity and durable activity across a wide range of doses administered to adults with recurrent glioblastoma multiforme (GBM) in a prior phase I study. The current multicenter phase II study was conducted to evaluate the activity and safety of cilengitide in GBM patients at first recurrence.Patients and MethodsEligible patients were randomly assigned to receive either 500 or 2,000 mg of cilengitide twice weekly on a continuous basis. Patients were assessed every 4 weeks. The primary end point was 6-month progression-free survival (PFS) rate. Secondary end points included PFS, overall survival (OS), and radiographic response, as well as quality-of-life and pharmacokinetic assessments.ResultsEighty-one patients were enrolled, including 41 on the 500-mg arm and 40 on the 2,000-mg arm. The safety profile of cilengitide was excellent, with no significant reproducible toxicities observed on either arm. Antitumor activity was observed in both treatment cohorts but trended more favorably among patients treated with 2,000 mg, including a 6-month PFS of 15% and a median OS of 9.9 months.ConclusionCilengitide monotherapy is well tolerated and exhibits modest antitumor activity among recurrent GBM patients. Additional studies integrating cilengitide into combinatorial regimens for GBM are warranted.

Phase II study of pembrolizumab plus SurVaxM for glioblastoma at first recurrence.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS2581-TPS2581 ◽  
Author(s):  
Manmeet Singh Ahluwalia ◽  
David M. Peereboom ◽  
Marci Ciolfi ◽  
Cathy Schilero ◽  
Brian Hobbs ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Clinical Activity ◽  
Leptomeningeal Disease ◽  
Free Survival ◽  
Apoptosis Protein ◽  
First Recurrence

TPS2581 Background: Glioblastoma is the most common primary malignant brain tumor with median survival of approximately 15-16 months. Following first recurrence, progression free survival at six months ~15%. There is no therapy in recurrent glioblastoma associated with any survival benefit and there is an urgent need for better therapeutic options. Immunotherapy is one promising option for patients with cancer. This is being explored in glioblastoma and a number of forms of active specific vaccination and immune checkpoint based approaches have been devised and are being investigated in glioblastoma. Methods: Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor. Survivin is a 16.5 kDa intracellular protein that belongs to the inhibitor of apoptosis protein (IAP) family. SurVaxM is a 15 amino acid antigenic peptide that targets surviving capable of binding several human MHC class I molecules. Primary Objective is to assess clinical activity of Pembrolizumab and SurVaxM in patients with recurrent glioblastoma using progression free survival at 6 months (PFS-6) as determined using RANO criteria. Secondary Objective(s) includes safety and tolerability of combination, response rates, progression free survival and overall survival. Exploratory Objective include measuring cellular and humoral immune responses during concurrent administration of Pembrolizumab and SurVaxM. This is a phase II study of two arms in patients with recurrent glioblastoma. Arm A is patients with first recurrence of glioblastoma who have failed prior chemotherapy and radiation but have not received any immunotherapy. Arm B is an exploratory arm of glioblastoma patients who have failed prior anti-PD1 therapy. This clinical trial will enroll 41 patients with glioblastoma at first recurrence (bevacizumab naïve) in arm 1.This will include a 6-patient toxicity/safety run-in. There will an exploratory cohort of 10 patients who have failed prior PD1 blockade for a total of 51 patients in 2 arms. Key inclusion criteria include diagnosis of glioblastoma, Age ≥18 years old, Previous first line treatment with at least radiotherapy with or without temozolomide and Documented first recurrence of GBM and Karnofsky performance status of 70 and normal organ function. Key exclusion criteria include more than one recurrence of GBM, presence of extracranial metastatic or leptomeningeal disease, patients with > 1 cm midline shift on imaging. Patients must not require > 10 mg daily of prednisone equivalent. Clinical trial information: NCT04013672 .

First-Line Chemotherapy With Cisplatin Plus Fractionated Temozolomide in Recurrent Glioblastoma Multiforme: A Phase II Study of the Gruppo Italiano Cooperativo di Neuro-Oncologia

2004 ◽  
Vol 22 (9) ◽  
pp. 1598-1604 ◽  
Author(s):  
Alba A. Brandes ◽  
Umberto Basso ◽  
Michele Reni ◽  
Francesca Vastola ◽  
Alicia Tosoni ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Hematologic Toxicity ◽  
Recurrent Glioblastoma Multiforme

Purpose Cisplatin and temozolomide (TMZ) are active in glioblastoma multiforme (GBM), with different profiles of toxicity. A bid regimen of TMZ achieves a strong inhibition of O6-alkylguanine DNA-alkyl transferase (AGAT), and cisplatin reduces AGAT activity in vitro, suggesting a possible synergic interaction. The primary end point of the present multicenter phase II study was progression-free survival (PFS) at 6 months (PFS-6); secondary end points included response, toxicity, and overall survival. Patients and Methods Chemotherapy-naive patients with GBM who experienced disease recurrence or progression after surgery and standard radiotherapy were eligible. Chemotherapy cycles consisted of cisplatin 75 mg/m2 on day 1, TMZ 130 mg/m2 bolus followed by nine doses of 70 mg/m2 every 12 hours (total of 5 days) from day 2 every 4 weeks. In the absence of hematologic toxicity, TMZ was escalated to 1,000 mg/m2 in 5 days. Results A total of 50 patients (median age, 53.4 years; range, 27 to 70 years; median Karnofsky performance status, 80; range, 60 to 100) were accrued in the study. PFS-6 was 34% (95% CI, 23% to 50%), and PFS-12 was 4% (95% CI, 0.3% to 16%). Median PFS was 18.4 weeks (95% CI, 13 to 25.9 weeks). Among 49 assessable patients, one complete response and nine partial responses were obtained, with an overall response rate of 20.4% (95% CI, 7.7% to 33%). Among 203 treatment cycles delivered, the most common grade 3 or grade 4 events included granulocytopenia in 7.9% of cycles, thrombocytopenia in 4%, and neurologic toxicity in three patients (6%). Conclusion The new cisplatin plus bid TMZ regimen appears active in chemotherapy-naive patients with recurrent GBM and incurs an acceptable toxicity.

scholarly journals Phase II study of XR5000 (DACA) administered as a 120-h infusion in patients with recurrent glioblastoma multiforme

2002 ◽  
Vol 13 (5) ◽  
pp. 777-780 ◽  
Author(s):  
C. Twelves ◽  
M. Campone ◽  
B. Coudert ◽  
M. Van den Bent ◽  
M. de Jonge ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme

Phase II study of ifosfamide, carboplatin and etoposide (ICE) in recurrent glioblastoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2066-2066
Author(s):  
T. Aoki ◽  
K. Nojima ◽  
T. Mizutani ◽  
M. Ishikawa ◽  
A. Takasu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
First Line ◽  
Open Label ◽  
Free Survival ◽  
Secondary Endpoints

2066 Background: To evaluate the efficacy and tolerability of ifosfamide, carboplatin and etoposide ( ICE ) in patients with recurrent glioblastoma. Methods: This was an open-label, single-center phase II trial. Forty-two patients with first recurrent glioblastoma after surgery, standard radiotherapy and a first-line temozolomide-based or ACNU-based chemotherapy, were enrolled.The primary endpoint was progression-free survival at 6 months ( PFS-6 ), and secondary endpoints were response rate, toxicity, and survival. Chemotherapy consisted of Ifosfamide ( 700 mg / m2 on day 1, 2 and 3 ), carbopaltin ( 100 mg / m2 on day 1 ), etoposide ( 70 mg / m2 on day 1, 2, and 3 ), every 6 weeks. Results: PFS-6 was 37 %. The median PFS was 17 weeks. Response rate was 27 %. Adverse events were generally mild ( grade 1 or 2 ) and consisted mainly of alopecia. Conclusions: This regimen is well tolerated and has activity in patients with recurrent glioblastoma. No significant financial relationships to disclose.

Phase II trial of high dose imatinib in recurrent glioblastoma multiforme (GBM) with platelet derived growth factor receptor (PDGFR) expression

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2056-2056 ◽  
Author(s):  
F. S. Viola ◽  
A. Katz ◽  
A. Arantes ◽  
A. Gaiger ◽  
C. Vasconcellos ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Significant Proportion ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Recurrent Glioblastoma ◽  
High Dose ◽  
Recurrent Glioblastoma Multiforme ◽  
Disease Stabilization ◽  
Ecog Ps

2056 Background: GBM are the most common primary brain tumors in adults. Despite available treatment they carry a poor prognosis with recurrences in most patients (pts) after initial therapy. PDGF signaling has been postulated to play a role in GBM transformation. We have demonstrated that PDGFRβ is expressed in tumor cells in 50% and in peritumoral endothelial cells in 65% of GBM (Barrios et al, abstract 11518, Proc ASCO 2006). Imatinib, an inhibitor of PDGFRa/β kinase activity could have therapeutic activity in these cases. Methods: We evaluated Imatinib in pts with recurrent GBM (previous radiation and chemotherapy) selected by PDGFR expression. Analysis of PDGFRa/β was performed by standard IHC. Positivity was considered in case of any qualitative expression. Pts were treated with 800 mg/day of Imatinib until tumor progression. All were on steroids and taking enzyme inducing antiepileptic drugs. Response was determined by MRI with spectroscopy and perfusion every 8 weeks according to RECIST criteria. Results: Twenty pts were enrolled (18 GBM, 2 AA). Median age: 51 (21–74), 7 were females. ECOG-PS at inclusion: 0 (3), 1 (10), 2 (7). All pts had expression of PDGFRa and 55% expressed PDGFRβ. Response data are available for all 20 pts. Main adverse events (all grade 1–2) were: edema (55%), nausea (50%), diarrhea and fatigue (35% each). We did not observe any PR but 13 pts (65%) showed disease stabilization. Median progression-free survival was 7.8 months with 60.8% of pts alive at 6 months; 6 months PFS was 52.2%. Conclusions: Imatinib was well tolerated in this group of poor prognosis highly pre-treated GBM pts demonstrating disease stabilization in a significant proportion of cases. These results, in a limited sample, compare favorably with historical data in similar populations. Selection of pts according to the specific molecular expression of their tumor may lead to better therapeutic results. No significant financial relationships to disclose.

MC044h, a phase II trial of sorafenib in patients (pts) with metastatic neuroendocrine tumors (NET): A Phase II Consortium (P2C) study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4504-4504 ◽  
Author(s):  
T. J. Hobday ◽  
J. Rubin ◽  
K. Holen ◽  
J. Picus ◽  
R. Donehower ◽  
...  
Keyword(s):  
Growth Factor ◽  
Neuroendocrine Tumors ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Uncontrolled Hypertension ◽  
Eligibility Criteria ◽  
Grade 3

4504 Background: Treatment options for metastatic NET, including islet cell carcinoma (ICC) and carcinoid tumor (CT), are limited. These tumors frequently express vascular endothelial growth factor receptor-2 (VEGFR-2) and platelet derived growth factor receptor receptor-β (PDGFR-β). Sorafenib, a small-molecule inhibitor of the VEGFR-2 and PDGFR-β tyrosine kinase domains, is a rational targeted therapy to evaluate in NET. Methods: Eligibility criteria included: ECOG PS = 2, = 1 prior chemotherapy, good organ function and signed informed consent. Prior interferon and prior or concurrent octreotide at a stable dose were allowed. Pts unable to take oral medications, with uncontrolled hypertension or with symptomatic coronary artery disease were excluded. Pts received sorafenib 400 mg po BID. Primary endpoint was response by RECIST in two cohorts (ie, CT and ICC) using separate 2-stage phase II designs. Results: 93 pts were enrolled: (50 CT, 43 ICC). For pts evaluable for the primary endpoint, 4 of 41 (10%) CT pts and 4 of 41 (10%) ICC pts had a PR. There were 3 minor responses (MR = 20–29% decrease in sum of target lesion diameters) in CT pts and 9 MRs in ICC pts for PR+MR rate of 17% for CT pts and 32% for ICC pts. For pts evaluable, 6-month progression-free survival was observed in 8/20 CT and 14/23 ICC pts. Grade 3–4 toxicity occurred in 43% of pts, with skin (20%), GI (7%) and fatigue (9%) most common. Translational studies from tumor tissue will be presented. Conclusions: Sorafenib at 400 mg po BID has modest activity in metastatic neuroendocrine tumors, with frequent grade = 3 toxicity. Supported by NOI CM6225. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document