PRECEDENT: A randomized phase II trial comparing EC145 and pegylated liposomal doxorubicin (PLD) in combination, versus PLD alone, in subjects with platinum-resistant ovarian cancer.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA5012b-LBA5012b ◽  
Author(s):  
R. W. Naumann ◽  
J. T. Symanowski ◽  
S. A. Ghamande ◽  
N. Y. Gabrail ◽  
L. Gilbert ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Interim Analysis ◽  
Folate Receptor ◽  
Pegylated Liposomal Doxorubicin ◽  
Ca 125 ◽  
Cancer Type ◽  
Platinum Resistant ◽  
Randomized Phase Ii

LBA5012b Background: EC145, a conjugate of folic acid and desacetylvinblastine hydrazide binds with high affinity to the folate receptor (FR), found on > 90% of epithelial ovarian cancers. This abstract reports interim data on an international randomized, phase II study of EC145 + PLD compared with PLD alone, in women with platinum-resistant ovarian cancer. An independent Data Safety Monitoring Board (DSMB) has conducted a prespecified interim analysis on PFS and safety with results reported herein. Methods: Women ≥ 18 with ECOG PS of 0-2 and ≤ 2 prior systemic cytotoxic regimens were randomized to receive EC145 (2.5 mg IV weeks 1 and 3) + PLD (50 mg/m2 IBW IV q 28 days) or PLD (50 mg/m2 IBW IV q 28 days) alone until progression or death. Results: The interim analysis occurred after the 46th event out of a planned study total of 95 progressions or deaths. Demographic characteristics at screening such as age, cancer type, residual tumor after debulking, prior therapy, CA-125 and time from diagnosis were balanced between arms. RECIST mean sum tumor length was longer for the combination arm (122.7 mm vs. 81.3 mm). There was no statistical difference between study arms with regard to total adverse events, serious adverse events, or the number of subjects reporting at least one treatment-emergent drug-related serious adverse event resulting in discontinuation. The Table displays the results of the interim analysis of PFS. At the interim, there is also a trend toward benefit in overall survival for the combination arm with HR = 0.425 (p value of 0.064). Conclusions: Results indicate a greater than doubling in median PFS for women with platinum-resistant ovarian cancer receiving EC145 and PLD over those receiving PLD alone. These interim data suggest that EC145 and PLD is the first combination to show a statistically significant delay in progression-free survival over standard therapy in women with platinum-resistant ovarian cancer. [Table: see text] [Table: see text]

PRECEDENT: A Randomized Phase II Trial Comparing Vintafolide (EC145) and Pegylated Liposomal Doxorubicin (PLD) in Combination Versus PLD Alone in Patients With Platinum-Resistant Ovarian Cancer

2013 ◽  
Vol 31 (35) ◽  
pp. 4400-4406 ◽  
Author(s):  
R. Wendel Naumann ◽  
Robert L. Coleman ◽  
Robert A. Burger ◽  
Edward A. Sausville ◽  
Elzbieta Kutarska ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Phase Ii Trial ◽  
Folate Receptor ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Platinum Resistant ◽  
Randomized Phase Ii

Purpose Vintafolide (EC145) is a folic acid–desacetylvinblastine conjugate that binds to the folate receptor (FR), which is expressed on the majority of epithelial ovarian cancers. This randomized phase II trial evaluated vintafolide combined with pegylated liposomal doxorubicin (PLD) compared with PLD alone. The utility of an FR-targeted imaging agent, 99mTc-etarfolatide (EC20), in selecting patients likely to benefit from vintafolide was also examined. Patients and Methods Women with recurrent platinum-resistant ovarian cancer who had undergone ≤ two prior cytotoxic regimens were randomly assigned at a 2:1 ratio to PLD (50 mg/m2 intravenously [IV] once every 28 days) with or without vintafolide (2.5 mg IV three times per week during weeks 1 and 3). Etarfolatide scanning was optional. The primary objective was to compare progression-free survival (PFS) between the groups. Results The intent-to-treat population comprised 149 patients. Median PFS was 5.0 and 2.7 months for the vintafolide plus PLD and PLD-alone arms, respectively (hazard ratio [HR], 0.63; 95% CI, 0.41 to 0.96; P = .031). The greatest benefit was observed in patients with 100% of lesions positive for FR, with median PFS of 5.5 compared with 1.5 months for PLD alone (HR, 0.38; 95% CI, 0.17 to 0.85; P = .013). The group of patients with FR-positive disease (10% to 90%) experienced some PFS improvement (HR, 0.873), whereas patients with disease that did not express FR experienced no PFS benefit (HR, 1.806). Conclusion Vintafolide plus PLD is the first combination to demonstrate an improvement over standard therapy in a randomized trial of patients with platinum-resistant ovarian cancer. Etarfolatide can identify patients likely to benefit from vintafolide.

Topotecan weekly versus routine 5-day schedule in patients with platinum-resistant ovarian cancer (TOWER): A randomized, two-stage phase-II study of the North-Eastern German Society of Gynaecological Oncology (NOGGO)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5526-5526 ◽  
Author(s):  
J. Sehouli ◽  
G. Oskay-Oezcelik ◽  
D. Stengel ◽  
A. du Bois ◽  
S. Markmann ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Interim Analysis ◽  
Therapeutic Index ◽  
Tumor Stage ◽  
Ca 125 ◽  
Study Endpoint ◽  
Primary Study ◽  
Two Stage ◽  
Platinum Resistant

5526 Background: Optimizing the therapeutic index (that is, maintaining drug effectiveness while reducing toxicity) is a major goal in chemotherapy for platinum-resistant ovarian cancer. Early phase-I/II studies suggest that weekly topotecan (T) might be effective and apparently better tolerated than the established 5-day regimen. As yet, no randomized comparison of both regimes was attempted. To prove the hypothesis of an improved therapeutic index with weekly T, we conducted a randomized, multicenter, two-stage phase-II trial, and herein present the data of the planned interim analysis. Methods: Pts with platinresistent ovarian and fallopian tube cancers or primary peritoneal carcinoma, measurable or assessable disease (GCIG-CA-125 response criteria), were eligible. Pts were randomized to receive either weekly T (d1,8,15/q28d, 4 mg/m2) or T from d1–5/q21d at a dose of 1.25 mg/m2. According to Gehan’s two-stage-design, both arms were handled as independent studies. Overall response rate (CR + PR) was defined as primary study endpoint, secondary endpoints of the interim analysis were toxicity and safety. Results: 28 pts in the weekly and 21 pts in the conventional group, enrolled at 38 centers form the basis of this report. 230 cycles of chemotherapy were evaluated for toxicity analyses. Median age was 61 years (range, 36 - 82 years). Demographic baseline characteristics, including tumor stage and grade were well balanced between treatment arms. There were 2/28 and 5/21 responses in weekly and the conventional arm, respectively (Risk Ratio [RR] 0.30, 95% confidence interval [CI] 0.06 - 1.40, p=0.122). The risk of early treatment termination due to tumor progression (RR 1.39, 95%CI 0.75 - 2.56), haematological (RR 0.20, 95% CI 0.01 - 3.97) or non- hematological toxicities (RR 1.96, 95% CI 0.18 - 20.83) did not differ significantly between groups. The only three events of neutropenic fever occurred in the conventional arm (RR 1.70, 95% CI 0.99 - 1.16). Conclusions: Weekly T is well tolerated and potentially active. The second stage of this study will require additional 46 patients each arm. Complete enrolment is expected to be accomplished in May 2007. No significant financial relationships to disclose.

Panitumumab and pegylated liposomal doxorubicin in platinum-resistant epithelial ovarian cancer with KRAS wild-type: The PaLiDo study, a phase II nonrandomized multicenter study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5052-5052 ◽  
Author(s):  
Karina Dahl Steffensen ◽  
Marianne Waldstrøm ◽  
Niels Pallisgaard ◽  
Bente Lund ◽  
Kjell Bergfeldt ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Response Rate ◽  
Pegylated Liposomal Doxorubicin ◽  
Ca 125 ◽  
Wild Type ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy ◽  
Dermatologic Toxicity

5052 Background: Ovarian cancer (OC) patients with platinum-resistant recurrent disease have few therapeutic options and the response rates are only 10-20% using non-cross-resistant chemotherapeutic agents. The increasing number of negative trials for OC treatment has prompted an evaluation of new biologic agents, which in combination with chemotherapy may result in improvement in survival. Panitumumab is a fully human monoclonal antibody specific to the epidermal growth factor receptor (EGFR). No previous studies have evaluated the effect of panitumumab in OC based on KRAS mutation status. The main purpose was to investigate the response rate in platinum-resistant, KRAS wild-type OC patients treated with pegylated liposomal doxorubicin (PLD) supplemented with panitumumab. Methods: Major eligibility criteria were confirmed stage I-IV primary epithelial ovarian/fallopian/peritoneal cancer patients with progression either during or within 6 months after end of first or second line platinum-based chemotherapy. Only patients with measurable disease by CA125 criteria and with KRAS wild type were eligible. Patients were treated with panitumumab 6 mg/kg day 1 and day 15 and with PLD 40 mg/m² day 1, every 4 weeks. Tumor assessment was performed at baseline and at every third cycle according to CA-125 criteria. Results: A total of 46 patients were enrolled by 6 study sites in this multi-institutional phase II trial. Within the population evaluable for response (N=33), there was 8 CA125 responders for an overall response rate of 24.3 %. Progression-free and overall survival in the intention-to-treat population (N=43) was 2.7 months (2.5-3.2 months, 95%CI) and 8.1 months (5.6-11.7 months, 95%CI), respectively. The most common treatment related grade 3 toxicities included skin toxicity (42%), fatigue (19%) and vomiting (12%). Conclusions: The combination of PLD and panitumumab demonstrates efficacy in platinum refractory/resistant patients although the dermatologic toxicity was considerable.

A randomized double-blind phase III trial comparing vintafolide plus pegylated liposomal doxorubicin (PLD) versus PLD plus placebo in patients with platinum-resistant ovarian cancer (PROCEED).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5613-TPS5613 ◽  
Author(s):  
R. Wendel Naumann ◽  
Lucy Gilbert ◽  
Anthonette M. Miller ◽  
Hong Ma ◽  
Sharad A. Ghamande ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Folate Receptor ◽  
Performance Status ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Double Blind ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy

TPS5613 Background: Folate receptor (FR) is expressed on the majority of epithelial ovarian cancers and FR expression appears to be a negative prognostic factor in this setting. Vintafolide (EC145) is a folate-conjugate designed to selectively deliver desacetylvinblastine monohydrazide (DAVLBH) to FR-expressing cells. 99mTc-Etarfolatide (EC20) is a technetium-labeled folate that identifies FR-expressing tumors. In a phase 2 study comparing vintafolide + PLD with PLD alone, the combination demonstrated a statistically and clinically significant delay in PFS (5.0 months) compared with PLD alone (2.7 months) in women with platinum-resistant ovarian cancer (Naumann et al, ASCO 2011). Data also indicated that 99mTc-etarfolatide may have utility for selecting patients most likely to benefit from vintafolide therapy. Methods: This is an international, randomized, double-blind, placebo-controlled phase 3 study of PLD ± vintafolide therapy compared in patients with primary or secondary platinum-resistant ovarian cancer (NCT01170650). Key eligibility criteria include: ≥18 years, pathology-confirmed epithelial ovarian, fallopian tube or primary peritoneal carcinoma, prior platinum-based chemotherapy, a RECIST v1.1 measureable lesion, and ECOG performance status 0 or 1. At baseline, patients undergo 99mTc-Etarfolatide imaging to identify FR-positive lesions and are subsequently randomized to the vintafolide ± PLD. PLD (50 mg/m2) adjusted for Ideal Body weight is administered on day 1 of a 4-week cycle and treatment continues until the maximum allowable cumulative dose (550 mg/m2) is reached or until disease progression or intolerable toxicity. Vintafolide (2.5 mg) or placebo is administered on days 1, 3, 5, 15, 17, and 19 of a 4-week cycle and treatment can continue for up to 20 cycles or until unacceptable toxicity or disease progression. The primary objective is to assess PFS based on investigator assessment (RECIST v1.1) in FR positive patients. Secondary objectives include OS, safety/tolerability, overall response rate, and disease control rate. Enrollment to the study is currently ongoing. Clinical trial information: NCT01170650.

INNOVATE: A phase II study of TTFields (200 kHz) concomitant with weekly paclitaxel for recurrent ovarian cancer—Updated safety and efficacy results.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5580-5580 ◽  
Author(s):  
Ignace Vergote ◽  
Roger von Moos ◽  
Luis Manso ◽  
Cristiana Sessa
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Cancer Patients ◽  
Electric Fields ◽  
Skin Irritation ◽  
Intermediate Frequency ◽  
Weekly Paclitaxel ◽  
Ca 125 ◽  
Serious Adverse Events ◽  
Platinum Resistant

5580 Background: TTFields are a non-invasive, regional antimitotic treatment modality, which have been approved for the treatment of recurrent and newly diagnosed glioblastoma by the FDA. TTFields act by delivering intermediate frequency alternating electric fields to the tumor, predominantly by disrupting the formation of the mitotic spindle during metaphase. INNOVATE was the first trial testing TTFields (200kHz) in ovarian cancer patients. Methods: Thirty-one recurrent, platinum-resistant, unresectable ovarian cancer patients were enrolled in the INNOVATE trial and treated with TTFields in combination with weekly paclitaxel. The primary endpoint was treatment emergent adverse events. Secondary endpoints included progression free-survival, overall survival and radiological response rate. Results: The median age was 60 (range – 45-77), most patients (77%) had serous histology. 52% had an ECOG score of 0. The median number of prior chemotherapy regimens was 4.1 (range 1-11). All patients were platinum-resistant, and 97% of patients received prior taxane-containing regimens. Ten (32%) patients suffered from serious adverse events (SAEs) during the study, none were related to TTFields. Of all reported SAEs, 31% were related to gastrointestinal disorders (ileus, jaundice and ascites) and 31% were respiratory events (dyspnea, pleural effusion and pulmonary embolism). Only one SAE which, related to the tumor, led to permanent discontinuation of the device. Most patients were reported to have mild-moderate, TTFields-related skin irritation, out of whom only two patients (6.4%) had severe-grade events. The median PFS was 8.9 months (95% CI 4.7, NA). Of the evaluable tumors, 25% had partial response and another 46.4% stable disease – a clinical benefit of 71.4%. Six patients (19.4%) had a CA 125 response, translating into a decrease of 50% or more in serum levels. The median OS was not reached. Conclusions: TTFields concomitant to weekly paclitaxel are tolerable and safe in heavily pre-treated platinum-resistant ovarian cancer ovarian cancer patients. These data support further clinical testing of TTFields with chemotherapy in ovarian cancer. Clinical trial information: NCT02244502.

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