MAESTRO: A randomized, double-blind phase III study of evofosfamide (Evo) in combination with gemcitabine (Gem) in previously untreated patients (pts) with metastatic or locally advanced unresectable pancreatic ductal adenocarcinoma (PDAC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 4007-4007 ◽  
Author(s):  
Eric Van Cutsem ◽  
Heinz-Josef Lenz ◽  
Junji Furuse ◽  
Josep Tabernero ◽  
Volker Heinemann ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Locally Advanced ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Double Blind ◽  
Phase Iii Study

Evofosfamide (TH-302) in combination with gemcitabine in previously untreated patients with metastatic or locally advanced unresectable pancreatic ductal adenocarcinoma: Primary analysis of the randomized, double-blind phase III MAESTRO study.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 193-193 ◽  
Author(s):  
Eric Van Cutsem ◽  
Heinz-Josef Lenz ◽  
Junji Furuse ◽  
Josep Tabernero ◽  
Volker Heinemann ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Significant Prognostic Factor ◽  
Primary Analysis ◽  
Eligibility Criteria ◽  
Double Blind

193 Background: Pancreatic ductal adenocarcinoma (PDAC) is invariably diagnosed at an advanced stage and has poor clinical outcome. Hypoxia is a significant prognostic factor in PDAC progression and is associated with poor prognosis. Evofosfamide (Evo, previously known as TH-302) is a hypoxia-activated prodrug of bromo-isophosphoramide mustard (Br-IPM) that is preferentially activated under hypoxic conditions. The addition of Evo to gemcitabine (Gem) significantly improved progression-free survival (PFS) in a randomized phase II trial in advanced PDAC (NCT01144455). Methods: MAESTRO is an international, randomized, double-blind, placebo-controlled phase III trial of Evo/Gem vs Placebo/Gem in patients (pts) with measurable, locally advanced unresectable or metastatic PDAC (NCT01746979). Evo and Gem were administered intravenously at a dose of 340 mg/m2 and 1,000 mg/m2, respectively, on days 1, 8, and 15 of a 28-day cycle. Treatment continued until disease progression. Key eligibility criteria included ECOG PS 0/1 and no neoadjuvant or adjuvant chemotherapy <6 months prior to entry. The primary endpoint was overall survival (OS) with the study designed to detect a HR of 0.75 with 90% power. Secondary endpoints included PFS and objective response rate (ORR), employing a hierarchical testing procedure with a 2-sided α=0.05 at each level. Results: A total of 693 pts were randomized to treatment with Evo/Gem (n=xxx) or Placebo/Gem (n=yyy). Baseline pt characteristics were similar between treatment arms. The OS HR was X.XX (95% CI: Y.YY, Z.ZZ; p=A.AAA). Median OS was AA.A months (m) for Evo/Gem vs BB.B m for Placebo/Gem. Median PFS was C.C m and D.D m, respectively (HR E.EE [95% CI: F.FF, G.GG; p = H.HHH). ORR was JJ.J% with Evo/Gem vs KK.K% with Placebo/Gem (p = L.LLL). Grade ≥3 adverse events (AEs) occurring in >5% of pts in treated with Evo/Gem were: TBC. Conclusions: The data from the MAESTRO trial will make an important contribution to our understanding of PDAC treatment. Clinical trial information: NCT01746979.

scholarly journals Breaking the Barrier—PEGylated Recombinant Human Hyaluronidase (PEGPH20)—A New Therapeutic Approach to the Treatment of Pancreatic Ductal Adenocarcinoma

2017 ◽  
Vol 13 (02) ◽  
pp. 107 ◽  
Author(s):  
Andrew Hendifar ◽  
Andrea Bullock ◽  
◽  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Immune Cells ◽  
Fluid Pressure ◽  
Tumor Stroma ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Double Blind ◽  
Potential Biomarker ◽  
Advanced Therapy ◽  
Recombinant Human Hyaluronidase

New therapeutic approaches are urgently needed to improve survival for patients with metastatic pancreatic ductal adenocarcinoma (PDA). This carcinoma is characterized by a hyaluronan (HA)-rich desmoplastic stroma that raises tumor interstitial fluid pressure (IFP), which in turn compresses the vasculature and impedes access of anti-cancer therapies and immune cells to tumor sites. It is this biophysical barrier that is the target for PEGylated recombinant human hyaluronidase (PEGPH20; pegvorhyaluronidase alfa), which degrades HA polymers to tetra- and hexa-saccharides to remodel the tumor stroma. In preclinical models, PEGPH20 reduced IFP, and expanded tumor vasculature to improve perfusion, which increased access for innate immune cells, antibodies and therapeutic agents. The results of a phase Ib study have suggested benefits in overall survival and progression-free survival (PFS) for patients with tumors that accumulate HA (termed HA-High) treated with a combination of gemcitabine and PEGPH20. A phase II study (HALO 109-202) demonstrated that HA could be a potential biomarker for identifying patients who may be most suitable for PEGPH20 treatment. HALO 109-202 showed positive outcomes for PFS especially in HA-High patients treated with PEGPH20 plus nab-paclitaxel and gemcitabine. A randomized, double-blind, phase III study (HALO 109-301) exploring the benefits of PEGPH20 in HA-High patients with PDA is ongoing. Other PEGPH20-based combinations are being investigated in multiple stroma-rich cancers, including lung, gastric, and breast. PEGPH20 is the most advanced therapy targeting the tumor stroma and has the potential to form the therapeutic backbone for the treatment of stroma-rich tumors.

Efficacy of CAB therapy in stage C prostate cancer: Exploratory analyses based on results of a double-blind, randomized, placebo-controlled phase III study of bicalutamide

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5154-5154 ◽  
Author(s):  
H. Akaza ◽  
Y. Arai ◽  
H. Kanetake ◽  
S. Naito ◽  
M. Usami
Keyword(s):  
Prostate Cancer ◽  
Locally Advanced ◽  
Phase Iii ◽  
Double Blind ◽  
Term Survival ◽  
Class Time ◽  
Phase Iii Study ◽  
Better Than ◽  
Observation Period

5154 Background: Although the efficacy of CAB in advanced prostate cancer (PC) has been demonstrated by the PCTCG and others, more evidence is required in locally advanced (Stage C) PC. The results of a Japanese P III study of bicalutamide in Stage C/D PC suggested the efficacy of CAB was better than monotherapy. When time to progression (TTP) was evaluated in Stage C and D separately, CAB had significant benefits in both stages and results in stage D were consistent with PCTCG data. Thus, this exploratory analysis was conducted to evaluate more thoroughly the efficacy of CAB in Stage C. Methods: 205 untreated PC patients with Stage C/D were randomized to CAB (goserelin 3.6 mg/4 weeks or leuprorelin 3.75 mg/4 weeks + bicalutamide 80 mg/day) or LHRHa monotherapy (same LHRHa + placebo). Among these patients, 99 had Stage C (52/47 on CAB/monotherapy). The median of the following parameters were calculated, and log-rank tests performed: TTP in all Stage C patients; TTP in Stage C patients by age, PSA value at diagnosis, and histopathological class; time to PSA normalization when normal level was defined as =4, =1 and =0.2 ng/mL. Results: The median observation period in Stage C patients was 144 weeks. The median TTPs by each parameter in Stage C are shown below. The median times to PSA normalization on CAB and monotherapy were 7 and 16 weeks (p<0.01), 8 and 93 weeks (p<0.01) and 20 weeks and NR (p<0.01) with normal values defined as =4, =1 and =0.2 ng/mL, respectively. Conclusions: These results suggest that CAB with bicalutamide possesses superior efficacy to LHRHa monotherapy in Stage C regardless of age, PSA value at diagnosis, or degree of tumor differentiation. It is suggested that CAB in Stage C could decrease PSA to lower levels in a shorter period than with LHRHa monotherapy. The study is ongoing to assess long term survival outcome. [Table: see text] No significant financial relationships to disclose.

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