Validation of Modeled Early Longitudinal Ca-125 Kinetics for Predicting Survival in Ovarian Cancer (Oc) Phase III Trials: Could the Failure of Adding Gemcitabine to Carboplatin-Paclitaxel (Ago-Ovar 9) Have Been Foreseen Earlier in the Trial?

On the basis of three large randomized phase III trials, the National Cancer Institute (NCI) issued a Clinical Announcement in January 2006 recommending that women with optimally debulked stage III ovarian cancer and their physicians consider a combination of intravenous (IV) and intraperitoneal (IP) chemotherapy. The combination of IV and IP chemotherapy is associated with a clinically significant benefit in survival, although it does also confer an increased risk of toxicity compared to IV chemotherapy alone. The NCI Clinical Announcement was issued as part of a broader educational campaign, designed in conjunction with professional societies, cancer centers, Clinical Trials Cooperative Groups, and cancer advocacy organizations. The further development of IP chemotherapy in ovarian cancer requires additional clinical and translational research

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Clinical trial in progress: Pivotal study of VB-111 combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.tps5599 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. TPS5599-TPS5599

Author(s):

Rebecca Christian Arend ◽

Bradley J. Monk ◽

Thomas J. Herzog ◽

Jonathan A. Ledermann ◽

Kathleen N. Moore ◽

...

Keyword(s):

Ovarian Cancer ◽

Clinical Trial ◽

Antiangiogenic Therapy ◽

Objective Response ◽

Phase Iii ◽

Weekly Paclitaxel ◽

Ca 125 ◽

Recist 1.1 ◽

Platinum Resistant ◽

Phase Iii Study

TPS5599 Background: Ofranergene obadenovec (VB-111) is a targeted anti-cancer gene therapy with a dual mechanism of action that includes a broad antiangiogenic effect and induction of a tumor directed immune response. A phase II trial in patients with platinum resistant ovarian cancer showed that VB-111 in combination with weekly paclitaxel was well tolerated and associated with a CA-125 Objective Response Rate (ORR) of 58% with a trend for improved survival. The favorable outcomes were associated with induction of an immunotherapeutic effect of tumor infiltration with CD-8 T cells. Based on these observations, a phase III study was initiated in collaboration with the GOG Foundation, Inc. Methods: Study NCT03398655 is an international, randomized, double-blind, placebo-controlled, phase III study. Eligible patients have recurrent platinum-resistant epithelial ovarian cancer with measurable disease (RECIST 1.1), and may have been previously treated with up to 5 prior lines of therapy. Patient are randomized 1:1 to receive VB-111 (1x1013 VPs) with weekly paclitaxel (80mg/m2), or weekly paclitaxel with placebo. Randomization is stratified by number of prior treatment lines, prior antiangiogenic therapy and platinum refractory disease status. The efficacy endpoints are OS, PFS and ORR by RECIST 1.1 and by CA-125 (GCIG criteria). A pre-planned interim analysis was performed by the DSMC in the first 60 patients evaluable for CA-125 response. The analysis met the pre-defined criteria of a CA-125 ORR (GCIG) in the treatment arm at least 10% higher than in the control arm. Study enrolment is ongoing and over 220 patients were enrolled in the US, EU, and Israel. Enrolment of the full sample size of 400 patients is expected to complete by the end of 2021. Clinical trial information: NCT03398655.

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First-line PARP inhibitors in ovarian cancer: summary of an ESMO Open - Cancer Horizons round-table discussion

ESMO Open ◽

10.1136/esmoopen-2020-001110 ◽

2020 ◽

Vol 5 (6) ◽

pp. e001110

Author(s):

Susana Banerjee ◽

Antonio Gonzalez-Martin ◽

Philipp Harter ◽

Domenica Lorusso ◽

Kathleen N Moore ◽

...

Keyword(s):

Ovarian Cancer ◽

Maintenance Therapy ◽

Parp Inhibitor ◽

Advanced Ovarian Cancer ◽

Round Table ◽

Parp Inhibitors ◽

Phase Iii ◽

European Medicines Agency ◽

First Line ◽

Phase Iii Trials

Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is the latest breakthrough in the management of newly diagnosed advanced ovarian cancer. The results of the SOLO-1 trial in 2018 led to European Medicines Agency and Food and Drug Administration approval of olaparib as first-line maintenance therapy in patients with BRCA1/2 mutation, establishing a new standard of care. Subsequently, the results of three phase III trials (PRIMA, PAOLA-1, VELIA) evaluating the use of first-line PARP inhibitors beyond patients with BRCA1/2 mutations and as combination strategies were presented in 2019, leading to the recent approval of maintenance niraparib irrespective of biomarker status and olaparib in combination with bevacizumab in homologous recombination deficiency-positive-associated advanced ovarian cancer. An ESMO Open - Cancer Horizons round-table expert panel discussed the four phase III trials of first-line PARP inhibitor therapy and how they are changing the clinical management of advanced ovarian cancer.

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Ovarian Cancer Phase III Trials

Oncology Times ◽

10.1097/01.cot.0000288484.35879.14 ◽

2007 ◽

Vol 29 (Supplement) ◽

pp. 8-10

Author(s):

Rabiya S. Tuma

Keyword(s):

Ovarian Cancer ◽

Phase Iii ◽

Phase Iii Trials

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Two Phase III trials show bevacizumab benefit for ovarian cancer

Oncology Times UK ◽

10.1097/01.otu.0000399898.13794.88 ◽

2011 ◽

Vol 8 (7) ◽

pp. 4

Author(s):

&NA;

Keyword(s):

Ovarian Cancer ◽

Phase Iii ◽

Two Phase ◽

Phase Iii Trials

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Corrigendum to “Phase III trials in ovarian cancer: The evolving landscape of front line therapy” [Gynecol. Oncol. 153 (2019) 436–444]

Gynecologic Oncology ◽

10.1016/j.ygyno.2019.12.007 ◽

2020 ◽

Vol 156 (2) ◽

pp. 512-513

Author(s):

R. Wendel Naumann ◽

Robert L. Coleman ◽

Jubilee Brown ◽

Kathleen N. Moore

Keyword(s):

Ovarian Cancer ◽

Phase Iii ◽

Front Line ◽

Line Therapy ◽

Phase Iii Trials

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Correlation of CA-125 and RECIST evaluation in recurrent ovarian cancer (ROC): Results from a randomized phase III study of trabectedin (T) with pegylated liposomal doxorubicin (PLD) versus PLD alone

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.5550 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 5550-5550

Author(s):

T. J. Herzog ◽

J. B. Vermorken ◽

E. Pujade-Lauraine ◽

J. Li ◽

E. Bayever ◽

...

Keyword(s):

Ovarian Cancer ◽

Predictive Value ◽

Objective Response ◽

Pegylated Liposomal Doxorubicin ◽

Phase Iii ◽

Ca 125 ◽

Open Label ◽

Significant Prolongation ◽

Phase Iii Study ◽

The Impact

5550 Background: OVA-301, an open-label, multicenter, randomized phase III study comparing the combination of T and PLD to PLD alone in 672 ovarian cancer patients, showed significant prolongation in Progression-Free Survival (PFS) and higher Objective Response (OR) in the combination arm (T-PLD) by three separate assessments, investigator assessment (IA), independent radiology (IR) and oncology review (IO). The purpose of this analysis is to examine: 1) the impact of early changes in CA-125 over the subsequent best OR by RECIST; 2) the concordance between best OR determined by CA-125 and RECIST; 3) the value of CA-125 to predict radiological response. Methods: Tumor assessments by imaging and CA-125 were performed at baseline, and every 8 weeks during study in both arms. Radiological tumor assessment, regardless of CA-125 changes, determined the study conduct. Early CA-125 changes were those assessed at the first and second evaluation. Analyses were based on “all randomized patients.” Results: Response rate by RECIST (IR)/CA-125 was 28%/48% for T-PLD vs. 19%/33% for PLD. The association between CA-125 and RECIST response was stronger for IA relative to IR/IO, with 79% concordance for both arms, 65% overall positive predictive value (PPV) and 89% negative predictive value (NPV) for IA and 74%/75% concordance, 46%/49% PPV and 93%/92% NPV for IR/IO. Early CA-125 changes were assessed in 514 patients. Early ≥25% CA-125 decreases in the first/second evaluation occurred in 85%/95% of RECIST responders in the T-PLD arm and in 81/82% responders treated with PLD. Conclusions: The predictive value of CA-125 response was high and similar in both arms. The addition of T to PLD resulted in superior efficacy in this patient population as assessed by IA, IR and IO, with a favorable trend for CA-125 response assessment. RECIST response was preceded by a significant CA-125 decrease in a high proportion of patients. [Table: see text]

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SOLO1 and SOLO2: Randomized phase III trials of olaparib in patients (pts) with ovarian cancer and a BRCA1/2 mutation (BRCAm).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.tps5616 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. TPS5616-TPS5616 ◽

Cited By ~ 13

Author(s):

Kathleen N. Moore ◽

Paul DiSilvestro ◽

Elizabeth S. Lowe ◽

Sally Garnett ◽

Eric Pujade-Lauraine

Keyword(s):

Ovarian Cancer ◽

Phase Iii ◽

Phase Iii Trials

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Phase III Trials of Standard Chemotherapy with or without Bevacizumab for Ovarian Cancer: A Meta-Analysis

PLoS ONE ◽

10.1371/journal.pone.0081858 ◽

2013 ◽

Vol 8 (12) ◽

pp. e81858 ◽

Cited By ~ 24

Author(s):

Mingyi Zhou ◽

Ping Yu ◽

Xiujuan Qu ◽

Yunpeng Liu ◽

Jingdong Zhang

Keyword(s):

Ovarian Cancer ◽

Meta Analysis ◽

Phase Iii ◽

Standard Chemotherapy ◽

Phase Iii Trials

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Intraperitoneal Chemotherapy for Ovarian Cancer: Overview and Perspective

Journal of Clinical Oncology ◽

10.1200/jco.2007.10.8167 ◽

2007 ◽

Vol 25 (20) ◽

pp. 2867-2872 ◽

Cited By ~ 25

Author(s):

Gautam Rao ◽

Marta Crispens ◽

Mace L. Rothenberg

Keyword(s):

Ovarian Cancer ◽

Abdominal Cavity ◽

Drug Distribution ◽

The United States ◽

Phase Iii ◽

Systemic Absorption ◽

Current Interest ◽

The Past ◽

Phase Iii Trials ◽

Large Phase

Intraperitoneal (IP) chemotherapy has theoretical, pharmacologic, and clinical advantages over intravenous (IV) chemotherapy in women with optimally debulked epithelial ovarian cancer confined to the abdominal cavity. Consistent, statistically significant improvements in both progression-free and overall survival have been demonstrated in three large phase III trials conducted in the United States during the past 10 years. Nevertheless, concerns over IP drug distribution and systemic absorption, technical challenges of IP catheter placement and the incidence of IP catheter-related complications, and the clinical relevance of these studies have limited the adoption of IP therapy in ovarian cancer. Current interest in the evaluation of molecularly targeted therapies should build on the progress that has been made through the use of IP chemotherapy in women with optimally debulked ovarian cancer.

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