Phase III Randomized Controlled Trial Comparing the Survival of Patients With Unresectable Hepatocellular Carcinoma Treated With Nolatrexed or Doxorubicin

2007 ◽  
Vol 25 (21) ◽  
pp. 3069-3075 ◽  
Author(s):  
Robert G. Gish ◽  
Camillo Porta ◽  
Lucian Lazar ◽  
Paul Ruff ◽  
Ronald Feld ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Karnofsky Performance Status ◽  
Controlled Trial ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Complete Response ◽  
Phase Iii ◽  
Study Objective

PurposeThe study objective was to compare the overall survival (OS) of patients with unresectable or metastatic hepatocellular carcinoma (HCC) treated with nolatrexed (NOL) or doxorubicin (DOX).Patients and MethodsPatients from North America, Europe, and South Africa (N = 445) with HCC were randomly assigned to receive NOL or DOX. Eligible patients had Karnofsky performance status (KPS) ≥ 60%, Cancer of the Liver Italian Program (CLIP) score ≤ 3, and adequate organ function. Primary end point was OS. Secondary end points included progression-free survival (PFS), objective response rates, and safety. The treatment groups were well-balanced with regards to age, sex, ethnic origin, and underlying liver disease. Randomization was stratified according to KPS and CLIP score.ResultsAt the time of the final analysis, 377 patients had died. Median OS was 22.3 weeks for NOL and 32.3 weeks for DOX (P = .0068). The hazard ratio was 0.753 in favor of DOX. Objective response rate (complete response [CR] plus partial response [PR]) was 1.4% for NOL and 4.0% for DOX. Median PFS was 12 weeks for NOL and 10 weeks for DOX (P = .7091). Median time to treatment failure was 8.4 weeks for NOL and 9.1 weeks for DOX (P = .0969). Grade 3 and 4 stomatitis, vomiting, diarrhea, and thrombocytopenia were more common in the NOL arm. Alopecia was more common in the DOX arm. More patients were withdrawn from study for toxicity in the NOL arm than in the DOX arm.ConclusionNOL showed minimal activity in this phase III trial. Further exploration at this dose and schedule in HCC is not warranted.

Final skin toxicity (ST) and patient-reported outcomes (PRO) results from PRIME: A randomized phase III study of panitumumab (pmab) plus FOLFOX4 (CT) for first-line metastatic colorectal cancer (mCRC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 531-531 ◽  
Author(s):  
Jean Yves Douillard ◽  
Salvatore Siena ◽  
Josep Tabernero ◽  
Ronald L. Burkes ◽  
Mario Edmundo Barugel ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Skin Toxicity ◽  
Least Square ◽  
Phase Iii ◽  
First Line ◽  
Ecog Performance Status ◽  
Patient Reported

531^ Background: Final PRIME results showed that pmab + CT significantly improved progression-free survival (PFS) and objective response rate vs CT alone for first-line wild type (WT) KRAS mCRC. Efficacy and PRO by ST severity from the final descriptive analysis of PRIME are presented. Methods: Patients (pts) had no prior chemotherapy for mCRC, ECOG performance status ≤ 2, and tumor tissue available for biomarker testing. The final analysis occurred 30 months after the last pt was enrolled; the primary endpoint was PFS; secondary endpoints included OS, objective response, and safety. Pts who received treatment and were alive without progression at day 28 were included in the ST analysis. Results: 1183 pts were randomized. 1057 pts with WT or MT KRAS mCRC met the criteria for inclusion in the ST analysis. Maximum grade ST was observed by day 28 in > 50% of pts. Results are shown ( table ). Overall differences in change from baseline of the least square means from a mixed effects model of the EQ-5D Overall Health Rating for pmab + CT (n = 285) minus CT alone (n = 294) and for ST gr 0-1 (n = 53) minus ST gr 2-4 (n = 232) were −1.069 (95% CI: −3.6277 to 1.4896) and 0.8971 (95% CI: ‐4.0224 to 5.8167), respectively. The overall safety profile was broadly comparable across ST groups and treatment arms. Conclusions: Pts with WT KRAS mCRC receiving pmab with ST gr 2-4 had longer PFS and OS vs pts receiving CT alone. PRO were not adversely affected by ST severity. [Table: see text]

Overall survival (OS) analysis from PRIME: Randomized phase III study of panitumumab (pmab) with FOLFOX4 for first-line metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3620-3620 ◽  
Author(s):  
Jean-Yves Douillard ◽  
Salvatore Siena ◽  
Josep Tabernero ◽  
Ronald L. Burkes ◽  
Mario Edmundo Barugel ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
First Line ◽  
Primary Analysis ◽  
Ecog Performance Status ◽  
Exon 2 ◽  
Kras Exon

3620 Background: The primary and final analyses of PRIME demonstrated that pmab + FOLFOX4 significantly improved progression-free survival (PFS) vs FOLFOX4 alone for first-line treatment of patients (pts) with wild-type (WT) KRAS exon 2 mCRC. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg every 2 weeks + FOLFOX4 or FOLFOX4 alone and had no prior chemotherapy for mCRC, ECOG performance status ≤ 2, and tumor tissue for biomarker testing. The primary endpoint was PFS by central assessment. Secondary endpoints included OS, objective response rate, and safety. KRAS exon 2 tumor status was determined by a blinded central lab prior to the primary analysis. This exploratory analysis of updated survival (>80% OS events) estimated the treatment effect of pmab + FOLFOX4 compared with FOLFOX4 alone on OS by KRAS exon 2 status. Previous analyses in pts with WT KRAS exon 2 tumor status reported OS with an event rate of 54% of pts in the primary analysis and 68% of pts in the final analysis. Results: 1183 pts were randomized and received treatment: 593 pts in the pmab + FOLFOX4 arm and 590 pts in the FOLFOX4 alone arm. The KRAS exon 2 ascertainment rate was 93%, consistent with the primary analysis. 535/656 pts (82%) with WT KRAS exon 2 mCRC had an OS event at the time of this analysis. Results are shown (Table). Conclusions: In this updated analysis, an improvement in OS was observed in pts with WT KRAS exon 2 mCRC treated with pmab + FOLFOX4 vs FOLFOX4 alone (p = 0.03). Median OS was reduced in pts with mutant (MT) KRAS mCRC (p = 0.16) and is consistent with previous analyses. Updated efficacy and safety results will be presented. KRAS testing is critical to select appropriate pts with mCRC for treatment with pmab. Clinical trial information: NCT00364013. [Table: see text]

Brivanib in Patients With Advanced Hepatocellular Carcinoma Who Were Intolerant to Sorafenib or for Whom Sorafenib Failed: Results From the Randomized Phase III BRISK-PS Study

2013 ◽  
Vol 31 (28) ◽  
pp. 3509-3516 ◽  
Author(s):  
Josep M. Llovet ◽  
Thomas Decaens ◽  
Jean-Luc Raoul ◽  
Eveline Boucher ◽  
Masatoshi Kudo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Controlled Trial ◽  
Objective Response ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Time To Progression ◽  
Fibroblast Growth Factor Receptors ◽  
Double Blind ◽  
Dual Inhibitor

Purpose Brivanib is a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors implicated in tumorigenesis and angiogenesis in hepatocellular carcinoma (HCC). An unmet medical need persists for patients with HCC whose tumors do not respond to sorafenib or who cannot tolerate it. This multicenter, double-blind, randomized, placebo-controlled trial assessed brivanib in patients with HCC who had been treated with sorafenib. Patients and Methods In all, 395 patients with advanced HCC who progressed on/after or were intolerant to sorafenib were randomly assigned (2:1) to receive brivanib 800 mg orally once per day plus best supportive care (BSC) or placebo plus BSC. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), and disease control rate based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and safety. Results Median OS was 9.4 months for brivanib and 8.2 months for placebo (hazard ratio [HR], 0.89; 95.8% CI, 0.69 to 1.15; P = .3307). Adjusting treatment effect for baseline prognostic factors yielded an OS HR of 0.81 (95% CI, 0.63 to 1.04; P = .1044). Exploratory analyses showed a median time to progression of 4.2 months for brivanib and 2.7 months for placebo (HR, 0.56; 95% CI, 0.42 to 0.76; P < .001), and an mRECIST ORR of 10% for brivanib and 2% for placebo (odds ratio, 5.72). Study discontinuation due to treatment-related adverse events (AEs) occurred in 61 brivanib patients (23%) and nine placebo patients (7%). The most frequent treatment-related grade 3 to 4 AEs for brivanib included hypertension (17%), fatigue (13%), hyponatremia (11%), and decreased appetite (10%). Conclusion In patients with HCC who had been treated with sorafenib, brivanib did not significantly improve OS. The observed benefit in the secondary outcomes of TTP and ORR warrants further investigation.

Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma

2009 ◽  
Vol 27 (6) ◽  
pp. 843-850 ◽  
Author(s):  
Melanie B. Thomas ◽  
Jeffrey S. Morris ◽  
Romil Chadha ◽  
Michiko Iwasaki ◽  
Harmeet Kaur ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Response Rate ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Study Objective ◽  
Advanced Hcc

Purpose The study objective was to determine the proportion of patients with hepatocellular carcinoma (HCC) treated with the combination of bevacizumab (B) and erlotinib (E) who were alive and progression free at 16 weeks (16-week progression-free survival [PFS16]) of continuous therapy. Secondary objectives included response rate, median PFS, survival, and toxicity. Patients and Methods Patients who had advanced HCC that was not amenable to surgical or regional therapies, up to one prior systemic treatment; Childs-Pugh score A or B liver function; Eastern Cooperative Oncology Group performance status 0, 1, or 2 received B 10 mg/kg every 14 days and E 150 mg orally daily, continuously, for 28-day cycles. Tumor response was evaluated every 2 cycles by using Response Evaluation Criteria in Solid Tumors Group criteria. A total of 40 patients were treated. Results The primary end point of PFS16 was 62.5%. Ten patients achieved a partial response for a confirmed overall response rate (intent-to-treat) of 25%. The median PFSevent was 39 weeks (95% CI, 26 to 45 weeks; 9.0 months), and the median overall survival was 68 weeks (95% CI, 48 to 78 weeks; 15.65 months). Grades 3 to 4 drug-related toxicity included fatigue (n = 8; 20%), hypertension (n = 6; 15%), diarrhea (n = 4; 10%) elevated transaminases (n = 4; 10%), gastrointestinal hemorrhage (n = 5; 12.5%), wound infection (n = 2; 5%) thrombocytopenia (n = 1; 2.5%), and proteinuria, hyperbilirubinemia, back pain, hyperkalemia, and anorexia (n = 1 each). Conclusion The combination of B + E in patients who had advanced HCC showed significant, clinically meaningful antitumor activity. B + E warrant additional evaluation in randomized controlled trials.

Efficacy of avelumab plus axitinib (A + Ax) versus sunitinib (S) by number of IMDC risk factors and tumor sites at baseline in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 302-302
Author(s):  
Yoshihiko Tomita ◽  
Robert J. Motzer ◽  
Toni K. Choueiri ◽  
Brian I. Rini ◽  
Hideaki Miyake ◽  
...  
Keyword(s):  
Risk Factors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Risk Groups ◽  
Phase Iii ◽  
Once Daily ◽  
Free Survival ◽  
To Receive

302 Background: In the phase III JAVELIN Renal 101 trial (NCT02684006), A + Ax demonstrated progression-free survival (PFS) and objective response rate (ORR) benefit across IMDC risk groups (favorable, intermediate, and poor) vs S in patients with previously untreated aRCC. Here we report efficacy of A + Ax vs S by number of IMDC risk factors (0, 1, 2, 3, and 4-6) and target tumor sites (1, 2, 3, and ≥4) at baseline from the second interim analysis of overall survival (OS). Methods: Patients were randomized 1:1 to receive A 10 mg/kg intravenously every 2 wk + Ax 5 mg orally twice daily or S 50 mg orally once daily for 4 wk (6-wk cycle). PFS and ORR per independent central review (RECIST 1.1) and OS were assessed. Results: At data cut-off (Jan 2019), median (m) follow-up for OS and PFS was 19.3 vs 19.2 mo and 16.8 vs 15.2 mo for the A + Ax vs S arm, respectively. The table shows OS, PFS, and ORR by number of IMDC risk factors and target tumor sites at baseline. A + Ax generally demonstrated efficacy benefit vs S across subgroups. Conclusions: With extended follow-up, A + Ax generally demonstrated efficacy benefit vs S across the number of IMDC risk factors and tumor sites at baseline in aRCC. OS was still immature; follow-up for the final analysis is ongoing. Clinical trial information: NCT02684006 . [Table: see text]

Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial

2020 ◽  
Vol 38 (3) ◽  
pp. 193-202 ◽  
Author(s):  
Richard S. Finn ◽  
Baek-Yeol Ryoo ◽  
Philippe Merle ◽  
Masatoshi Kudo ◽  
Mohamed Bouattour ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Interim Analysis ◽  
Statistical Significance ◽  
Study Drug ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Double Blind ◽  
Previously Treated

PURPOSE Pembrolizumab demonstrated antitumor activity and safety in the phase II KEYNOTE-224 trial in previously treated patients with advanced hepatocellular carcinoma (HCC). KEYNOTE-240 evaluated the efficacy and safety of pembrolizumab in this population. PATIENTS AND METHODS This randomized, double-blind, phase III study was conducted at 119 medical centers in 27 countries. Eligible patients with advanced HCC, previously treated with sorafenib, were randomly assigned at a two-to-one ratio to receive pembrolizumab plus best supportive care (BSC) or placebo plus BSC. Primary end points were overall survival (OS) and progression-free survival (PFS; one-sided significance thresholds, P = .0174 [final analysis] and P = .002 [first interim analysis], respectively). Safety was assessed in all patients who received ≥ 1 dose of study drug. RESULTS Between May 31, 2016, and November 23, 2017, 413 patients were randomly assigned. As of January 2, 2019, median follow-up was 13.8 months for pembrolizumab and 10.6 months for placebo. Median OS was 13.9 months (95% CI, 11.6 to 16.0 months) for pembrolizumab versus 10.6 months (95% CI, 8.3 to 13.5 months) for placebo (hazard ratio [HR], 0.781; 95% CI, 0.611 to 0.998; P = .0238). Median PFS for pembrolizumab was 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 2.5 to 4.1 months) for placebo at the first interim analysis (HR, 0.775; 95% CI, 0.609 to 0.987; P = .0186) and 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 1.6 to 3.0 months) at final analysis (HR, 0.718; 95% CI, 0.570 to 0.904; P = .0022). Grade 3 or higher adverse events occurred in 147 (52.7%) and 62 patients (46.3%) for pembrolizumab versus placebo; those that were treatment related occurred in 52 (18.6%) and 10 patients (7.5%), respectively. No hepatitis C or B flares were identified. CONCLUSION In this study, OS and PFS did not reach statistical significance per specified criteria. The results are consistent with those of KEYNOTE-224, supporting a favorable risk-to-benefit ratio for pembrolizumab in this population.

TM1-1 Seizure prophylaxis in gliomas (SPRING): a phase III randomised controlled trial comparing prophylactic levetiracetam versus no prophylactic anti-epileptic drug in glioma surgery

2019 ◽  
Vol 90 (3) ◽  
pp. e8.2-e8
Author(s):  
MD Jenkinson ◽  
C Watts ◽  
AG Marson ◽  
R Hill ◽  
K Murray ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Karnofsky Performance Status ◽  
Controlled Trial ◽  
Performance Status ◽  
Phase Iii ◽  
Glioma Surgery ◽  
Seizure Prophylaxis ◽  
Anti Epileptic Drug ◽  
Seizure Rate ◽  
Randomised Controlled

ObjectivesThere is no consensus regarding the need for prophylactic anti-epileptic drug (AED) in seizure-naive newly-diagnosed glioma patients. Data regarding prophylactic AED use are scant and inconclusive from older, small studies that enrolled patients with brain metastases, benign tumours and gliomas. A definitive randomised controlled trial (RCT) is needed to determine whether the policy of prophylactic AED therapy reduces the risk of first seizures in this population.DesignMulti-centre RCT.SubjectsInclusion criteria: i. seizure-naive, ii. supratentorial glioma suitable for surgery (biopsy/resection), iii. age ≥16 years; iv. Karnofsky performance status >60.MethodsPatients are randomised 1:1. Levetiracetam 500 mg bd for 2 weeks, increased to 750 mg bd thereafter for 1 year. Non-blinded. No placebo. Primary Outcome: one year risk of first seizure. Secondary outcomes: time to first seizure, time to first tonic-clonic seizure, mood, fatigue, quality of life, progression free survival, overall survival and incremental cost per QALY. Estimate of 1 year seizure rate in glioma after surgery is 20%. Based on a reduction in seizure rate to 10% a total of 806 patients will be recruited.ResultsGrant awarded by NIHR. Feasibility questionnaire demonstrated prophylactic AED rarely used. Neurosurgeons willing to randomise. 15 UK centres have expressed interest in participating.ConclusionsSPRING will establish class I evidence for the use of seizure prophylaxis in glioma surgery. The trial will open to recruitment in January 2019.

Phase III Study of VCAP-AMP-VECP vs. Biweekly CHOP in Aggressive Adult T-Cell Leukemia-Lymphoma (ATLL): Japan Clinical Oncology Group Study, JCOG9801.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 812-812 ◽  
Author(s):  
Kunihiro Tsukasaki ◽  
Takuya Fukushima ◽  
Atae Utsunomiya ◽  
Syuichi Ikeda ◽  
Masato Masuda ◽  
...  
Keyword(s):  
Cox Regression ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Rank Test ◽  
P Value ◽  
Minimization Method ◽  
Adult T Cell Leukemia ◽  
Non Hodgkin Lymphoma

Abstract Background: In our study for non-Hodgkin lymphoma (NHL) in 1980’s (JCOG8701), human T-lymphotropic virus type-1- associated ATLL was the poorest prognostic subtype in NHL. The complete response (CR) rate was 42%, the median survival time (MST) was 8 months, and the 4-yr overall survival (OS) was 12% (Proc ASCO13:378, 1994). Our previous phase II study (JCOG9303) of G-CSF-supported, dose-intensified multi-agent chemotherapy with VCAP (vincristine, cyclophosphamide, doxorubicin, prednisolone), AMP (doxorubicin, ranimustine, prednisolone) and VECP (vindesine, etoposide, carboplatin, prednisolone) with intrathecal prophylaxis for aggressive ATLL, showed promising results with response rate (RR) of 81% and MST of 13 months (Br J Haematol113:375,2001). To test the superiority of this VCAP-AMP-VECP regimen over biweekly-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone), we conducted a phase III trial. Methods: Previously untreated patients (pts) with aggressive ATLL, acute-, lymphoma- or unfavorable chronic-type, were randomized either to receive 6 courses of VCAP-AMP-VECP every 4 weeks (arm A) or 8 courses of biweekly-CHOP (arm B) with minimization method balancing performance status and institution. Both regimens were supported with G-CSF and intrathecal prophylaxis using cytarabine, methotrexate and prednisolone. Eligibility included preserved organ functions and aged 15–69 years. Primary endpoint was OS to be compared by log-rank test. Assuming 60 eligible pts in each arm, the study had 0.8 power to detect a 15% difference in 3-year OS at 0.05 one-sided alpha. Results: 118 pts (57 in arm A, 61 in arm B) were randomized between 07/98 and 10/03. Median follow-up time in all randomized pts was 11.0 months at 12/04. 72 % of the pts responded, with 23 pts achieving CR (40%) and 18 achieving partial response (PR; 32%) in arm A. The RR was 66%, with 15 pts achieving CR (25%) and 25 achieving PR (41%) in arm B. The median progression-free survival (PFS) time and PFS at one-year in arm A were 7.0 months and 28.1%, respectively, whereas 5.4 months and 16.2% in arm B. The MST and OS at 3 years in arm A were 12.7 months and 23.6%, respectively, whereas 10.9 months and 12.7% in arm B. Log-rank p-value for primary end point, OS, was 0.085. After adjustment of patients’ characteristics at registration by Cox regression, the p value became 0.029 because of unbalanced prognostic factors such as bulky lesion. In arm A vs. arm B, %G4 neutropenia, %G4 thrombocytopenia and %G4 infection were 98% vs. 83%, 74% vs. 17% and 7% vs. 3%, respectively. Three toxic deaths were reported in arm A. Conclusions: These results demonstrate that VCAP-AMP-VECP yields longer OS time than biweekly-CHOP but with higher toxicity profiles that are acceptable, and suggest that the former regimen should be the standard therapy for aggressive ATLL.

Cetuximab in combination with cisplatin or carboplatin and 5-fluorouracil (5-FU) in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R&M SCCHN) (EXTREME)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5537-5537 ◽  
Author(s):  
J. B. Vermorken ◽  
R. Mesia ◽  
M. E. Vega-Villegas ◽  
E. Remenar ◽  
R. Hitt ◽  
...  
Keyword(s):  
Overall Survival ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Prognostic Significance ◽  
Safety Data ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Safety Analysis ◽  
Data Safety Monitoring Board ◽  
Phase Iii

5537 Background: The epidermal growth factor receptor (EGFR) is expressed in nearly all SCCHN and carries a strong prognostic significance, providing the rationale for using EGFR-targeted agents, such as cetuximab, in this indication. This study assesses the efficacy and safety of cetuximab in combination with chemotherapy commonly used in the treatment of R&M SCCHN. Methods: Patients (pts) were enrolled into this phase III trial from December 2004 to December 2005 and randomized either to Group A: cetuximab (first dose 400 mg/m2 then 250 mg/m2 weekly) plus a maximum of 6 three-weekly cycles of cisplatin (100 mg/m2 IV on day 1) or carboplatin (AUC 5, day 1) and 5-FU (1000 mg/m2/day continuous infusion for the first 4 days of each cycle) or to Group B: cisplatin or carboplatin with 5-FU as before. Cetuximab was administered until progression or unacceptable toxicity. Primary endpoint is overall survival time; secondary endpoints are progression-free-survival, response rate, disease control rate, safety, and Quality of Life. It was planned to randomize a total number of 420 pts in order to detect a difference in improvement in overall survival of 2.5 months. Results: At the end of the recruitment,440 pts have been randomized, to date 320 pts are under treatment, 21 have withdrawn from the study and 99 have completed the study. The Data Safety Monitoring Board (DSMB) has performed an independent preplanned safety analysis from the first 140 pts, 138 pts of whom were treated. Patients were followed for a minimum of 6 weeks: M/F122/16, median age57 years [range, 38–79],median Karnofsky performance status (KPS) 80 [range, 70–100]. In this safety analysis, there were 14 deaths, none of which were treatment related. The most frequent drug related grade 3–4 toxicity was mainly represented by neutropenia, thrombocytopenia and anemia. Conclusions: The DSMB evaluated baseline and safety data, found no reason to stop the trial and recommended continuation of the study. [Table: see text]

Randomized phase III trial of regorafenib in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) progressing despite prior treatment with at least imatinib (IM) and sunitinib (SU): GRID trial.

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA10008-LBA10008 ◽  
Author(s):  
George D. Demetri ◽  
Peter Reichardt ◽  
Yoon-Koo Kang ◽  
Jean-Yves Blay ◽  
Heikki Joensuu ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Controlled Trial ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Double Blind Study ◽  
Open Label ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Multikinase Inhibitor

LBA10008 Background: Oral multikinase inhibitor regorafenib (REG) demonstrated substantial activity in a phase II trial in pts with GIST after failure of both IM and SU (J Clin Oncol. 2011; 29:606s; abstr 10007). This phase III, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of REG for this unmet clinical need. Methods: Eligible pts had metastatic and/or unresectable GIST, objective failure of both prior IM and SU (progressive disease [PD] on, or intolerance to, IM and PD on SU), ≥1 measurable lesion, ECOG performance status 0 or 1. Pts were randomized 2:1 to receive best supportive care plus either REG 160 mg po once daily (3 wks on/1 wk off) or placebo (PL). The primary endpoint was progression-free survival (PFS) (modified RECIST 1.1, independent central review). Secondary endpoints included overall survival (OS), disease control rate (DCR, defined as rate of partial response [PR] plus stable disease [SD] lasting for ≥12 wks), response rate and duration, safety and correlative genotype analyses. At time of PD, pts were eligible for unblinding and crossover to open-label REG. Results: Between Jan and Aug of 2011, 234 pts were screened; 199 were randomized (REG: 133, PL: 66). Pts were stratified at randomization according to number of prior systemic therapies and geographical region. Baseline characteristics were balanced between the two arms. The primary endpoint was met: median PFS was 4.8 months for REG vs. 0.9 months for PL. Hazard ratio for PFS was 0.27 (95% CI, 0.18-0.39), p<0.0001. PFS rates at 3 and 6 months were 60% and 38% for REG vs. 11% and 0% for PL. DCR was 53% (REG) vs. 9% (PL).The HR for OS was 0.77 (p=0.20) with 85% PL pts having crossed over to REG. The most common > grade 3 treatment-emergent AEs in the REG arm during double-blind study were hypertension (28%), hand-foot skin reaction (21%), and diarrhea (8%). Conclusions: This randomized trial demonstrated that REG significantly improved PFS and DCR in pts with advanced GIST after failure of at least prior IM and SU. REG was well tolerated, with AEs as expected for this class and manageable with dose modifications.

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