scholarly journals CTNI-47. PHASE II STUDY OF ABEMACICLIB IN RECURRENT GBM PATIENTS WITH CDKN2A/B LOSS AND INTACT RB

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii53-ii53
Author(s):  
Eudocia Lee ◽  
Alona Muzikansky ◽  
Isabel Arrillaga-Romany ◽  
Ugonma Chukwueke ◽  
Timothy Cloughesy ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Recurrent Glioblastoma ◽  
Open Label ◽  
Cyclin Dependent Kinases ◽  
Best Response ◽  
Common Grade ◽  
First Relapse ◽  
Grade 3 ◽  
Recurrent Gbm

Abstract Deregulation of the cyclin-dependent kinases (CDK) 4 and 6 (cdk4/6)–cyclin D-INK4—retinoblastoma protein (Rb) signaling pathway is among the most common aberrations found in glioblastoma (GBM) with more than 80% of patients estimated to be affected. We conducted an open label, multi-center, phase II trial of abemaciclib in participants with recurrent glioblastoma (GBM) at their first relapse and with documented evidence of CDKN2A/B loss and intact RB from archival tissue. A total of 32 patients enrolled on the non-surgical arm of the study with 13 women (40.63%) and median KPS 90 [range 60–100]. The PFS6 rate was 9.37% [95% CI, 2.4%, 22.27%], median PFS 55 days [95% CI, 49, 56], and median OS 384 days [95% CI, 228, 488]. Out of 31 evaluable patients, best response was PR 1 (3.2%), SD 11 (35.5%), and PD 19 (61.3%). The most common grade 3 or higher toxicities at least possibly related to abemaciclib included leukopenia (21.9%), neutropenia (18.6%), lymphopenia (9.4%), and thrombocytopenia (6.3%). Abemaciclib has minimal activity in this preselected recurrent GBM population. Correlative studies from the surgical arm of this study are pending.

NABTT-0702: A phase II study of R-(-)-gossypol (AT-101) in recurrent glioblastoma multiforme (GBM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2010-2010 ◽  
Author(s):  
J. B. Fiveash ◽  
S. A. Chowdhary ◽  
D. Peereboom ◽  
T. Mikkelsen ◽  
L. B. Nabors ◽  
...  
Keyword(s):  
Phase Ii ◽  
Troponin T ◽  
Recurrent Glioblastoma ◽  
Recurrent Glioblastoma Multiforme ◽  
Potent Inducer ◽  
Response Data ◽  
Best Response ◽  
Grade 3 ◽  
The Impact ◽  
Recurrent Gbm

2010 Background: R-(-)-gossypol (AT-101) is an oral bcl-2 family protein inhibitor (Bcl-2, Bcl-XL, Mcl-1, Bcl-W) and potent inducer of proapoptotic proteins. A prior study of racemic gossypol demonstrated objective responses in patients with malignant glioma. The objectives of this trial were to determine the efficacy and safety of the more active (-) enantiomer of gossypol (AT-101) in patients with recurrent GBM. Methods: Fifty-six patients with recurrent GBM were enrolled in this multi-institution phase II clinical trial through the NABTT CNS consortium designed to detect a 33% increase in overall survival (OS, primary endpoint) from 5 to 6.65 months with Power/Alpha 80%/0.01. All patients had received prior radiation and none had received more than two prior treatments. Patients taking P450-inducing anticonvulsants were not eligible. AT-101 was administered at 20 mg PO per day for 21 of 28 days in repeated cycles. Radiographic assessment of tumor response was made at q 8-week intervals. Results: Fifty-six patients were enrolled with a median age of 59 (range 34–79) and KPS of 80 (range 60–100). Grade 3 or greater adverse events possibly or probably related to AT-101 included fatigue (n = 2), ileus (n = 1), elevated cardiac troponin T levels (n = 1), elevated GGT (n = 1), and thrombocytopenia (n = 1). Response data is available for 43 patients. OS determination is ongoing. Seven patients (16%) had stable disease as the best response. One partial response (centrally reviewed) was observed. No complete responses were observed. Although treatment is ongoing, two patients are without progression after more than 7 months of therapy. Conclusions: AT-101 is well tolerated and without unique toxicities in patients with recurrent GBM. Further follow-up will determine the impact of AT-101 on OS and whether any tissue correlate is predictive of efficacy. No significant financial relationships to disclose.

Regorafenib in patients with refractory metastatic pancreatic cancer: a Phase II study (RESOUND)

2019 ◽  
Vol 15 (35) ◽  
pp. 4009-4017
Author(s):  
Silvia Bozzarelli ◽  
Lorenza Rimassa ◽  
Laura Giordano ◽  
Simona Sala ◽  
Maria Chiara Tronconi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Clinical Trial Registration ◽  
Free Survival ◽  
End Point ◽  
Best Response ◽  
Cancer Types ◽  
Grade 3 ◽  
Experienced Grade

Aim: Regorafenib may be active in different cancer types. This Phase II trial included patients with various refractory cancer types treated with regorafenib. Here, we report the results of the pancreatic adenocarcinoma cohort. Methods: The primary end point was progression-free survival (PFS) rate at 8 weeks; further investigation of regorafenib would be warranted with a PFS rate ≥50%. Results: A total of 20 patients were enrolled. The best response was stable disease in four patients (20%). The 8-week PFS rate was 25% with a median PFS of 1.7 months (95% CI: 1.5–2.0). A total of 13 patients (65%) experienced grade 3–4 treatment-related adverse events. Conclusion: The study did not meet its primary end point. Further investigation of regorafenib monotherapy in this setting is not recommended. Clinical Trial Registration: NCT02307500

Advancements in Treatment for Newly Diagnosed Frail and Elderly Myeloma Patients: A Systematic Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5589-5589
Author(s):  
Syed Maaz Abdullah ◽  
Tariq Iqtidar Sadiq Syed ◽  
Muhammad Salman Faisal ◽  
Awais Ijaz ◽  
Syeda Sabeeka Batool ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Phase Iii ◽  
Two Phase ◽  
Phase Iii Trial ◽  
Frail Patients ◽  
Best Response ◽  
Drug Regimens ◽  
Grade 3

Introduction: About 60% newly diagnosed multiple myeloma (NDMM) cases are above age of 60 years. The paucity of studies exclusively targeting management of frail patients has led to persistence of therapeutic uncertainties. With data on more than ten thousand patients, purpose of this review is to summarize the available therapeutic options with emphasis on recent advances for treatment of frail and elderly, transplant ineligible NDMM patients. Methods: We performed a comprehensive literature search on June 1st, 2019 on PubMed, Cochrane Library and ClinicalTrials.gov. We used the MeSH terms: 'Multiple Myeloma' and 'Frail Elderly', with associated entry words. Search yielded 71 studies regarding our topic of interest. Following PRISMA guidelines and subsequent screening by two reviewers, we shortlisted 19 ongoing/completed studies (n=10297) and included data from these studies in our systematic review. Results: Two/Three Drug regimens: Among the two drug regimens [Table 1], Lenalidomide (R) and Dexamethasone (D) (RD) combination has been most widely studied (n=1445). RD yielded objective response rate (ORR) of 81.3%, complete response (CR) or above of 24.9% and progression free survival (PFS) of 31.9 months in a phase III trial (Usmani, 2019) (n=369). Facon et al. (2019) [n=368] used Daratumumab (Dara)+R+D (DaraRD) which exhibited the best response overall with an ORR of 92.9%, CR of 47.6%, VGPR of 31.8% while the PFS was not reached till study end point. However, >grade 3 neutropenia developed in 50% patients. Three-drug regimen of Bortezomib(V)+Melphalan(M)+Prednisolone(P) (VMP) has been the most widely studied regimen (n=1059) in four phase II/III clinical trials. In a phase II trial (Kizaki, 2016) (n=87), VMP yielded a PFS of 36 months and CR of 25%. In a Phase II trial by Larocca et al (2016, n=148), 3 cohorts (VP, V+ Cyclophosphamide (C) +P and VMP respectively) were studied. Best response was achieved by VMP with ORR of 86%, PFS of 17.1 months and CR of 14%, compared with VCP (ORR=67%, PFS=15.2 months and CR=2%) and VP (ORR=64%, PFS=14 months, CR=8%). However, the discontinuation rate (DR) due to AEs for VMP was relatively high (20%). A phase III trial (San-Miguel, 2018) (n=955) compared Carfilzomib(K)+M+P (KMP) against VMP. Median PFS was found to be 22.3 months with KMP Vs 22.1 months with VMP. Grade ≥3 AE rates were 74.7% for KMP and 76.2% for VMP. Thus, the results showed no significant difference between both regimens. Thalidomide (T) has also been used in three drug combinations in two phase II/III trials (n=667). Ixazomib(I)+T+D (ITD) in a phase II trial (Abildgaard, 2017) (n=120) revealed an ORR of 75% compared to ORR of 62% in a phase III trial (Benboubker et al, 2014) (n=547) using MPT. Notable >grade 3 AEs with ITD were infections (15%) and cardiac abnormalities (10%) while with MPT were >grade 3 neutropenia (45%) and infections (17%). A retrospective analysis by Facon et al. (2015, n=1517) comparing RD Vs MPT demonstrated that RD reduced the risk of progression or death by 21% compared to MPT in frail patients. 2. Four Drug Regimens: Four drug regimens have also been used in transplant-ineligible patients in two phase II/III trials (n=583). Mateos et al. (2015, n=233) conducted a phase II trial in which patients were treated with VMP+RD (VMPRD). 49 frail patients based on Age >80 years (IMWG criteria) had ORR of 68%, PFS of 25 months and CR of 10%, with a DR of 63% due to toxicity or informed consent withdrawal. However, in the ALCYONE trial (San-Miguel, 2017) (n=350), use of Dara+VMP (DaraVMP) resulted in ORR of 90.9%, ≥CR of 42.6%, VGPR of 28.6% and PFS was not reached till study end point. Furthermore, the DR due to AEs for DaraVMP was also lesser (4.9%). Various trials [Table 2] are being conducted to establish correlation of frailty scores with parameters of efficacy. Conclusion: Management of frail and elderly NDMM patients is challenging as there is need to individualize therapy for this group. Novel agents such as lenalidomide, bortezomib and daratumumab have shown promising efficacy when used as combination therapies with other conventional agents. Intensity of treatment and efficacy goals should be tailored to the functional capacity and tolerance of each individual patient. There is need for focused clinical trials for this group in terms of greater recruitment into clinical trials to establish better correlation between frailty status and efficacy, and consolidating evidence for improved patient care. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

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 oral gimatecan in adults with recurrent glioblastoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2009-2009
Author(s):  
J. Hu ◽  
P. Y. Wen ◽  
L. E. Abrey ◽  
C. Fadul ◽  
J. Drappatz ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Single Agent ◽  
Recurrent Glioblastoma ◽  
Hematologic Toxicity ◽  
Radiographic Response ◽  
Daily Dose ◽  
Grade 3 ◽  
Experienced Grade

2009 Background: Gimatecan is a highly lipophilic oral camptothecin analogue with impressive preclinical activity in glioma models. Methods: We conducted a multicenter two-stage phase II trial to evaluate the efficacy of gimatecan in adults with recurrent glioblastoma. Eligibility criteria included ≤1 prior treatment for recurrent disease, age ≥18, ECOG performance status 0 or 1, and normal organ function. Patients taking enzyme-inducing anti-seizure medications were excluded. Gimatecan 1.22 mg/m2 was given orally once daily for 5 consecutive days during each 28-day cycle. Radiographic response was evaluated by MRI after every second cycle. The primary endpoint of the study was 6 months PFS. A Simon's 2-stage design was used in which 19 patients were evaluated in the first stage, with an additional 36 patients accrued if > 4 patients in stage 1 achieved 6 month PFS. Results: A total of 29 patients were enrolled in the study, with median age of 58 years (range, 25–77 years); 58.6% female; all of whom had received prior surgery, radiation therapy, and at least one regimen of chemotherapy. The daily dose was reduced to 1.0 mg/m2 after four of the first 10 patients experienced grade 4 hematologic toxicity. One patient was removed from trial due to toxicity (grade 3 leukopenia and thrombocytopenia). Treatment delay occurred in 11 patients (38%) and dose reduction was necessary in eight patients (28%). Treatment-related grade 3/4 toxicities included thrombocytopenia (17.2%), leukopenia (17.2%), and neutropenia (10.3%). Only 1/19 patients treated with 1.0 mg/m2/day experienced grade 3/4 hematologic toxicity. The 18% reduction in the daily dose resulted in a 19% decrease in the concentration of total gimatecan in plasma prior to administration of the fifth daily dose (56 ± 23 vs. 45 ± 20 ng/mL) and a 33% decrease in the AUC for dose 5 (8.0±4.8 vs. 5.3±4.2 ng*h/mL). Only one patient had a partial radiographic response by the modified Macdonald criteria and stable disease was the best response in 13 patients. All other patients had progressive disease after two cycles of therapy. Only three patients (12%) were progression-free at 6 months. Median time to progression was 12.0 weeks (95% CI: 7.0, 17.0). Conclusions: Treatment with single-agent gimatecan 1.0 mg/m2/day for 5 days, repeated every 28-days showed minimal efficacy. [Table: see text]

A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: A trial of the PMH Phase II Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5576-5576
Author(s):  
S. Welch ◽  
H. J. Mackay ◽  
H. Hirte ◽  
G. F. Fleming ◽  
R. Morgan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Open Label ◽  
Second Stage ◽  
Best Response ◽  
Grade 3 ◽  
Ecog Ps

5576 Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Vascular endothelial growth factor (VEGF) overexpression in EC correlates with poor outcome, thus targeting VEGF is a rational therapeutic approach. We have conducted a two-stage open-label phase II study in advanced EC with sunitinib, an oral tyrosine kinase inhibitor of multiple VEGF receptors. Methods: Eligible pts have recurrent or metastatic EC and have received up to 1 prior chemotherapy (CT) regimen for metastatic disease. Sunitinib is given at 50 mg daily (OD) for 4 consecutive weeks (wks) followed by 2 wks off. Dose could be reduced to 37.5 mg OD and then 25 mg OD in the setting of toxicity. Imaging is repeated every 12 wks. Primary objectives are objective response rate (ORR by RECIST) and rate of 6-month progression-free survival (PFS). If 1 or more responses occur in the first 15 evaluable pts, the study would continue to a second stage (total = 30 pts). Secondary objectives are time to progression (TTP), overall survival (OS), and safety. Results: We report the results of the first stage of this study. Sixteen pts have been treated (median age: 63; range 41–74) with 37 cycles of sunitinib (median 2; range: 1–7). Baseline ECOG PS was 0 (7 pts), 1 (8 pts), or 2 (1 pt). Histology was endometrioid (7 pts), serous (5 pts), clear cell (1 pt), or mixed/other (3 pts). Most pts had high-grade histology (G3: 8; G2: 4; G1: 2; GX: 2). Nine pts had prior adjuvant CT, 8 pts had 1 prior CT for advanced EC, 4 pts had prior hormones and 7 pts had prior radiotherapy. Partial response was achieved by 2 pts (ORR = 12.5%), and 2 other pts had a best response of stable disease; 3 of these pts remained progression-free > 6 months. Median TTP = 2.5 months (95% CI: 2.47-NR), and median OS = 6.2 months (95% CI: 5.1-NR). Grade 3/4 adverse events (AE) in >10% of pts were fatigue (7 pts, 44%) and hypertension (5 pts, 31%). Dose reduction was required for 11 of 16 pts (69%). Two pts were inevaluable after receiving <2 cycles due to AE (grade 4 hyponatremia; grade 3 fatigue) and 1 other pt has yet to complete 2 cycles. Conclusions: Sunitinib shows preliminary activity in EC. This trial will proceed to a second stage of accrual to further explore the efficacy and safety of sunitinib in advanced EC. [Table: see text]

Phase II study of PX-866 in recurrent glioblastoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2051-2051
Author(s):  
Marshall W. Pitz ◽  
Mary Valeria MacNeil ◽  
David R. Macdonald ◽  
Ankineedu Saranya Kakumanu ◽  
Brian Thiessen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Recurrent Glioblastoma ◽  
Pi3k Inhibitor ◽  
Stage I ◽  
Stage Ii ◽  
Response Data ◽  
Grade 3 ◽  
Recurrent Gbm

2051 Background: Glioblastoma (GBM) is the most aggressive malignancy of the central nervous system. The majority of GBM have genetic changes that increase the activity of the phosphatidylinositol-3-OH kinase (PI3K) signal transduction pathway, critical for cell motility, proliferation, and survival. We present the interim results of PX-866, an oral PI3K inhibitor, in patients (pts) with recurrent GBM. Methods: Pts with histologically confirmed GBM at first recurrence after treatment with chemoradiation and adjuvant temozolomide are given PX-866 8 mg daily on this single-arm phase II study. MRI and clinical exam are done every 8 weeks to determine treatment response. The trial has a 2-stage design with dual endpoints of objective response and early progression (within 8 weeks). In Stage I, 15 pts are evaluated and if 0 responses and 10 or more early progressions are seen, enrolment will stop. Otherwise, Stage II will enrol another 15 pts for efficacy analysis. Tumour tissue is collected for analysis of potential markers of PI3K inhibitory activity (PTEN, EGFRvIII, PIK3CA mutations). Results: Seventeen pts have been enroled to date: 14 evaluable for response and 15 for toxicity. Median age was 54 years (range 35-70), with 7 females and 10 males. No pts had received treatment for recurrent GBM, and median time between initial diagnosis and study enrolment was 300 days (range: 113-447 days). Pts have received a median of one 8-week cycle of PX-866 (range: 1-4). Twelve pts have discontinued therapy, 9 due to disease progression and 3 due to grade 3/4 liver enzyme abnormalities. Other adverse effects have included fatigue (10 pts/1 grade 3), diarrhea (6 pts/3 grade 3), nausea (7 pts/0 grade 3), vomiting (6 pts/0 grade 3), lymphopenia (14 pts/3 grade 3). Stage I response data are premature; it is not yet known if the trial will continue to Stage II. Archival tissue is available on all patients and is undergoing analysis. Conclusions: This is one of the first trials of a PI3K inhibitor in pts with recurrent GBM. PX-866 has been relatively well tolerated. Stage I response data are premature; while it is not yet known if the criteria will be met to continue to Stage II, prolonged SD has been observed in some pts. The correlative biomarker assays underway will be important to understand this observation.

Randomized phase II study of S-1/CDDP plus TSU-68 versus S-1/CDDP in patients with advanced gastric cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 72-72
Author(s):  
Kensei Yamaguchi ◽  
Wasaburo Koizumi ◽  
Hisashi Hosaka ◽  
Yasutaka Takinishi ◽  
Norisuke Nakayama ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Phase Ii ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Open Label ◽  
Parallel Group ◽  
Common Grade ◽  
Grade 3 ◽  
Endothelial Growth Factor

72^ Background: Gastric cancer (GC) is the second leading cause of cancer death in Japan as well as globally. Effective treatment of GC remains a therapeutic challenge. Although in the AVAGAST trial, bevacizumab was found to offer no survival benefit. Angiogenesis continues to be the standard treatment for GC, and thus, clinical trials on many anti-angiogenic drugs have been conducted. TSU-68 (orantinib) is an oral, angiokinase inhibitor targeting the vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor β, and fibroblast growth factor receptor 1. The present study evaluated the progression-free survival (PFS) and pharmacokinetics (PK) of TSU-68 in combination with Japanese standard S-1 and cisplatin (S-1/CDDP) in patients with advanced GC. Methods: In this open-label, multicenter, randomized, controlled, parallel-group, phase II trial, patients were randomized to Arm A (S-1/CDDP) or Arm B (TSU-68 plus S-1/CDDP). All patients received oral S-1 (40-60 mg/m2) twice daily for 21 days followed by a 14 day rest plus intravenous CDDP (60 mg/m2) on Day 8, repeated every 35 days. In Arm B pts received oral TSU-68 (400 mg/dose) alone, twice daily by addition 35 days. The primary endpoint was PFS. Results: In total, 93 patients were enrolled. For Arm A [male:female ratio], n=47 [35:11]; Arm B, n=45 [30:15]; the respective median age was 63.5 and 62.0 years. The median PFS was 7.0 and 6.8 months in Arms A and B, respectively (HR, 1.23; 95%CI, 0.74 to 2.05; P=0.425); the respective response rates were 56.5% and 62.2%. The most common grade 3/4 toxicities were neutropenia (Arms A and B, 34.8% and 31.1%) and hemoglobin (Arms A and B, 26.1% and 48.9%). There were no differences in other toxicities between the 2 arms, both treatments were tolerated, and no treatment-related deaths were observed. In the PK study, although Arm B had a significantly lower plasma exposure to FT, CDHP, and Oxo compared to Arm A, the exposure to 5-FU was not different between the 2 arms. The exposure to CDDP in Arm B was significantly but slightly lower than that in arm A. Conclusions: Thus,TSU-68 plus S-1/CDDP therapy did not prolong PFS of patients with advanced GC as compared with S-1/CDDP. Clinical trial information: JapicCTI-101327.

Phase II trial of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma (HCC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 240-240 ◽  
Author(s):  
Aiwu Ruth He ◽  
Anteneh Tesfaye ◽  
Daniel Smith ◽  
John Marshall ◽  
Michael J. Pishvaian ◽  
...  
Keyword(s):  
Dna Repair ◽  
Disease Progression ◽  
Cancer Progression ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Common Grade ◽  
Grade 3

240 Background: The combination of the imidazotetrazine derivative temozolomide (TMZ) and poly(ADP-ribose) polymerase inhibitor veliparib (ABT-888) has shown in vivo activity against a variety of tumor types through the alkylating effects of TMZ and DNA repair inhibition by ABT-888. To date, no studies have examined the combination of TMZ and ABT-888 in treating advanced HCC refractory to sorafenib. Methods: This is a single arm Phase II trial. Eligible HCC patients have Child Pugh A/B cirrhosis and have failed prior treatment with sorafenib either through intolerance or disease progression. All patients have received ABT-888 40 mg daily on days 1-7 and Temozolomide 150 mg/m2 daily on days 1-5 in 28 day cycles for a maximum of 6 cycles. Tumor response is analyzed every 2 cycles using RECIST criteria. The primary endpoint is time to disease progression. The trial is being conducted using a modified Simon’s two-stage design optimal design as implemented by Hanfelt, et al. Results: The trial is currently in Simon Stage 1 with 16 patients recruited: 9 patients have stopped the study due to disease progression, 3 patients are still on protocol, and 4 patients stopped the study for reasons other than disease progression. 7 patients had disease progression at two months, 1 patient had cancer progression at 4 months, and 1 patient had disease progression at 16 months. Median time to progression in these 9 patients was 56 days (range 42-486 days). The four patients that stopped the study prematurely were for the following reasons: hiccups/dehydration, Mallory-Weiss tear secondary to refractory nausea, intraperitoneal bleeding from exophytic HCC lesion, and development of hepatorenal syndrome in a paracentesis-dependent patient. The most common grade 3 toxicities in this cohort so far have been nausea/vomiting (in 2 subjects), and anemia/thrombocytopenia (in 2 subjects). Defects in DNA repair pathways are being tested from the liver biopsy in the patient who had response to TMZ and ABT-888 for 16 months. Conclusions: The combination of TMZ and ABT-888 is fairly tolerated in patients with advanced HCC. So far, the treatment did not show activities in majority of patients with advanced HCC. Clinical trial information: NCT01205828.

Randomized, open-label, phase II study comparing five-weekly S-1 plus cisplatin (SP) with tri-weekly capecitabine plus cisplatin (XP) in chemotherapy-naïve patients with HER2 negative advanced gastric cancer (AGC): OGSG 1105 HERBIS-4A trial.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 102-102
Author(s):  
Atsushi Takeno ◽  
Youichi Makari ◽  
Shunji Endo ◽  
Jin Matsuyama ◽  
Ryohei Kawabata ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Open Label ◽  
Group 13 ◽  
Common Grade ◽  
Open Label Phase ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
To Receive

102 Background: This phase II study aimed to investigate the safety and efficacy of XP compared to SP in the first-line treatment of HER2 negative AGC. Methods: Patients were randomly assigned to receive either SP (S-1 at 40–60 mg twice daily for 21 days plus cisplatin at 60 mg/ m2 on day 8, every 5 weeks) or XP (capecitabine 1,000 mg/m2 twice daily for 14 days plus cisplatin 80 mg/m2 on day 1, every 3 weeks). Primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), and adverse events. Results: 84 eligible patients were randomly assigned to receive SP ( N = 41) or XP ( N = 43). No statistical difference was observed in overall RR between the SP and XP groups [51.2% (95% CI, 35.1% to 67.1%) vs. 53.5% (95% CI, 37.7% to 68.8%), P = 1.000]. Despite not significant, however, SP vs. XP showed a trend toward better PFS [median, 5.9 months vs. 4.1 months; hazard ratio (HR), 0.763; 95% CI, 0.462 to 1.259; P = .284] and OS (median, 13.5 months vs. 10.0 months; HR, 0.776; 95% CI, 0.485 to 1.244; P = .290). This trend in the SP vs. XP comparison was more pronounced in TTF (median, 4.5 months vs. 3.1 months; HR, 0.651; 95% CI, 0.421 to 1.006; P = .052). Common grade 3 to 4 hematological toxicities were neutropenia and anemia (SP group, 23% and 23%; XP group, 35% and 28%). Grade 3-4 anorexia and hyponatremia were more frequently seen in the XP group (31% and 16%) compared to the SP group (13% and 5%). Treatment-related deaths occurred in one patient (2.3%) in the XP group. Conclusions: XP failed to demonstrate the superior efficacy over SP. Higher incidence of severe toxicities by XP suggests SP as the standard 1st line chemotherapy for HER2 negative AGC in Japan. Clinical trial information: UMIN000006755.

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