A randomized phase II evaluation of weekly gemcitabine plus pazopanib versus weekly gemictabine alone in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5532-5532 ◽  
Author(s):  
Linda R. Duska ◽  
Jubilee Brown ◽  
Danijela Jelovac ◽  
Kathleen N. Moore ◽  
William P. McGuire ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tyrosine Kinases ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Open Label ◽  
Phase 2 Trial ◽  
Platinum Resistant ◽  
Valuable Treatment ◽  
Inhibition Of Angiogenesis ◽  
To Receive

5532 Background: Inhibition of angiogenesis is a valuable treatment strategy for ovarian cancer. Pazopanib (paz) is a potent angiogenic small molecular inhibitor of the tyrosine kinases VEGRF-1, -2, -3, PDGFR, c-kit and has shown activity as a single agent in ovarian cancer. We designed a trial to assess the benefit of adding paz to gemcitabine (gem) in patients with recurrent, advanced ovarian cancer. Methods: An open-label, randomized, multi-site, phase 2 trial was conducted (NCT01610206) including patients with platinum resistant or sensitive ovarian cancer with up to 3 prior lines of chemotherapy, and measurable or evaluable disease. Patients were randomly assigned (1:1) to receive weekly gem 1000 mg/m2 with or without paz 800 mg QD and stratified according to platinum sensitivity and number of prior lines (1 vs 2 or 3). The primary endpoint was PFS. Intent-to-treat was defined as all eligible patients who receive any protocol treatment with analysis based on randomized arm. Results: As of 3/2017, we randomized 148 and treated 146 patients (target sample size 148 eligible patients who receive any protocol treatment). 75 (46 platinum resistant, 61%) were randomly assigned to receive gem/paz and 71 (41 platinum resistant, 58%) to receive gem only. 110 patients (75%) had received 2 or 3 prior lines. There were no unexpected toxicities or deaths. Adverse events were more common in the gem/paz group. The most common grade 3–4 AEs (gem/paz vs gem) were: neutropenia (25 [33%] vs 15 [21%]), fatigue (7 [10%] vs 1 [2%]), hypertension (11 [15%] vs 1 [1%]), elevated alanine aminotransferase (8 [11%] vs 0), thrombocytopenia (9 [12%] vs 12[3%]) and anemia (7 [9%] vs 2 [3%]). There were 2 GI perforations in the paz arm. Median time on therapy was 12 weeks (range 1-55 weeks). Of the 138 patients off study to date, 30 (22%) were for AE’s (23 on gem/paz arm). Conclusions: The gem/paz combination is tolerable in this population, with patients tolerating multiple cycles with manageable toxicity. Median follow-up and PFS data will be presented after 122 events (progression or death) have occurred per protocol (currently 117 events). Clinical trial information: NCT01610206.

Nonpegylated liposome-encapsulated doxorubicin (NPLED) and cyclophosphamide in the treatment of platinum-resistant ovarian cancer: Final results of a phase II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15544-e15544
Author(s):  
Daniela Sambataro ◽  
Melania Caruso ◽  
Concetta Di Blasi ◽  
Giuseppe Lavenia ◽  
Salvatore Asero ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Single Agent ◽  
Progression Free Survival ◽  
Median Number ◽  
Open Label ◽  
Open Label Study ◽  
Free Survival ◽  
Resistant Refractory ◽  
Platinum Resistant

e15544 Background: Platinum resistant-refractory ovarian cancer (PRROC) patients have a poor outcome; single-agent therapy is still the gold standard, with overall response rate lesser than 20% and progression-free-survival is not higher than 4 months. Methods: We tested safety and activity of a two-drugs-regimen containing NPLED and cyclophosphamide in a phase II open label study. From October 2007 to October 2011 thirty-two patients with platinum-resistant/refractory disease were enrolled. Enrolled patients were pretreated with a median number of 2 lines of chemotherapy, ranging from 1 to 5. NPLED and cyclophosphamide were administered at the dose of 60 mg. and 600 mg p.s.m. respectively. Results: Patients received a median number of three cycles of chemotherapy. A total of 145 cycles were administered: as G3 toxicities we registered emesis (6%), diaorrhea (3%), asthenia, and alopecia. No grade 4 adverse events occurred. Among the 30 patients evaluable for response we observed 5 (17%) partial responses and 10 (33%) stable diseases. The median progression-free-survival was 13 weeks and the median survival was 46 weeks. Conclusions: These results are similar to other data reported in literature. In conclusion we may affirm that the association of NPLED and cyclophosphamide is active and safe when administered in PRROC, but it don’t modify the prognosis of this subset of patients.

Phase II Study of Carboplatin, Paclitaxel, and Bevacizumab With Maintenance Bevacizumab As First-Line Chemotherapy for Advanced Müllerian Tumors

2010 ◽  
Vol 28 (1) ◽  
pp. 154-159 ◽  
Author(s):  
Richard T. Penson ◽  
Don S. Dizon ◽  
Stephen A. Cannistra ◽  
Maria R. Roche ◽  
Carolyn N. Krasner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Single Agent ◽  
Area Under The Curve ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Ca 125 ◽  
Open Label ◽  
Peritoneal Cancer ◽  
Open Label Phase

Purpose New strategies are needed to improve outcomes for patients with advanced ovarian cancer. Bevacizumab is a recombinant humanized monoclonal antibody that neutralizes vascular endothelial growth factor but is associated with GI perforations (GIPs) in patients with recurrent disease. Patients and Methods An open-label, phase II clinical trial was conducted in newly diagnosed patients with stage ≥ IC epithelial müllerian tumors. Patients received intravenous (IV) carboplatin (area under the curve = 5), paclitaxel (175 mg/m2 IV), and bevacizumab (15 mg/kg IV) for six to eight cycles on day 1 every 21 days. Bevacizumab was omitted in the first cycle and continued as a single agent for 1 year. Results Sixty-two women participated in this study. Fifty-one patients (82%) were optimally surgically cytoreduced before treatment. The median age was 58 years (range, 18 to 77 years). Forty-five women (73%) had ovarian cancer, 10 (16%) had peritoneal cancer, four (6%) had fallopian tube cancers, and three (5%) had uterine papillary serous tumors. The majority of patients (90%) had stage III or IV disease. A median of 17 maintenance cycles (range, 0 to 25+ cycles) of bevacizumab (556 cycles) were administered with mild toxicity. Treatment was associated with two pulmonary embolisms and two GIPs, all occurring during the chemotherapy phase of treatment (364 total cycles). No grade 4 toxicities were seen during maintenance bevacizumab treatment. Radiographic responses were documented in 21 (75%) of 28 women with measurable disease (11 complete responses and 10 partial responses), with CA-125 responses in 76% of patients (11 complete responses, 21%; and 35 partial responses, 55%). The progression-free survival rate at 36 months was 58%. Conclusion The regimen of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab is feasible, safe, and worthy of future study in advanced ovarian cancer.

scholarly journals [18F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer

2019 ◽  
Vol 47 (5) ◽  
pp. 1239-1251 ◽  
Author(s):  
Rohini Sharma ◽  
Pablo Oriol Valls ◽  
Marianna Inglese ◽  
Suraiya Dubash ◽  
Michelle Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Combination Therapy ◽  
Single Agent ◽  
Progression Free Survival ◽  
Platinum Resistance ◽  
Open Label ◽  
Intention To Treat ◽  
Resistant Refractory ◽  
Platinum Resistant ◽  
Pet Tracer

Abstract Background Angiogenesis is a driver of platinum resistance in ovarian cancer. We assessed the effect of combination pazopanib and paclitaxel followed by maintenance pazopanib in patients with platinum-resistant/refractory ovarian cancer. Integrins αvβ3 and αvβ5 are both upregulated in tumor-associated vasculature. [18F]Fluciclatide is a novel PET tracer that has high affinity for integrins αvβ3/5, and was used to assess the anti-angiogenic effect of pazopanib. Patients and methods We conducted an open-label, phase Ib study in patients with platinum-resistant/refractory ovarian cancer. Patients received 1 week of single-agent pazopanib (800 mg daily) followed by combination therapy with weekly paclitaxel (80 mg/m2). Following completion of 18 weeks of combination therapy, patients continued with single-agent pazopanib until disease progression. Dynamic [18F]fluciclatide-PET imaging was conducted at baseline and after 1 week of pazopanib. Response (RECIST 1.1), toxicities, and survival outcomes were recorded. Circulating markers of angiogenesis were assessed with therapy. Results Fourteen patients were included in the intention-to-treat analysis. Complete and partial responses were seen in seven patients (54%). Median progression-free survival (PFS) was 10.63 months, and overall survival (OS) was 18.5 months. Baseline [18F]fluciclatide uptake was predictive of long PFS. Elevated baseline circulating angiopoietin and fibroblast growth factor (FGF) were predictive of greater reduction in SUV60,mean following pazopanib. Kinetic modeling of PET data indicated a reduction in K1 and Ki following pazopanib indicating reduced radioligand delivery and retention. Conclusions Combination therapy followed by maintenance pazopanib is effective and tolerable in platinum-resistant/refractory ovarian cancer. [18F]Fluciclatide-PET uptake parameters predict clinical outcome with pazopanib therapy indicating an anti-angiogenic response.

Phase 2 trial of tisotumab vedotin in platinum-resistant ovarian cancer (innovaTV 208).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS5602-TPS5602 ◽  
Author(s):  
Haider Mahdi ◽  
Steven Robert Schuster ◽  
David M. O'Malley ◽  
Donna M. McNamara ◽  
Reshma A. Rangwala ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Primary Endpoint ◽  
Human Monoclonal Antibody ◽  
Single Agent ◽  
Ca 125 ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Platinum Resistant ◽  
Platinum Based Chemotherapy ◽  
Increased Risk

TPS5602 Background: Ovarian cancer (OC) is the most lethal gynecologic cancer, accounting for ≈185,000 deaths worldwide in 2018. Most patients (pts) initially respond to platinum-based chemotherapy (chemo), but more than 50% of pts recur. Pts who recur in ≤6 months have platinum-resistant OC (PROC), which is associated with poor prognosis. Standard therapy for PROC includes chemo ± bevacizumab (bev). However, many pts receive single-agent chemo, which demonstrates limited response and survival (≈12% ORR, 3-4 mo PFS, ≈12 mo OS). Therefore, there is an urgent need for novel therapeutic strategies. Tissue factor (TF) is a novel oncogenic target expressed in OC. Tisotumab vedotin (TV) is a first-in-class antibody drug conjugate comprising a TF-targeted fully human monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. TV has shown encouraging antitumor activity and a manageable safety profile in PROC in the multicohort phase 1/2 innovaTV 201 study. innovaTV 208 is a multicenter, open-label, phase 2 trial with a safety run-in phase for a dose-dense regimen (DDR) evaluating the efficacy and safety of TV in pts with PROC. Methods: innovaTV 208 will enroll ≈142 adult pts with platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer; measurable disease by RECIST v1.1; and ECOG score 0-1. Eligible pts must have received bev-containing treatment for OC. Pts with platinum-refractory disease, increased risk of bleeding, active ocular surface disease, or grade > 1 peripheral neuropathy will be excluded. A safety run-in phase for the DDR will be performed in up to 12 pts who received ≤5 prior treatment regimens for PROC. In the DDR, TV will be given at previously decided lower doses IV 3Q4W for the same dose intensity as the standard 1Q3W dose; the primary endpoint is incidence of DLTs. In phase 2, pts who received ≤1 prior cytotoxic chemo regimen for PROC will be randomized to receive TV administered as IV 1Q3W or as IV 3Q4W, if shown to be tolerable. The primary endpoint for phase 2 is confirmed ORR by RECIST v1.1. Secondary endpoints include DOR, time to response, DCR, CA-125 response rate by GCIG criteria, PFS, OS, pharmacokinetics, and safety. Clinical trial information: NCT03657043.

Phase II study of front-line dovitinib (TKI258) versus sorafenib in patients (Pts) with advanced hepatocellular carcinoma (HCC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 237-237 ◽  
Author(s):  
Ann-Lii Cheng ◽  
Sumitra Thongprasert ◽  
Ho Yeong Lim ◽  
Wattana Sukeepaisarnjaroen ◽  
Tsai-Sheng Yang ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Disease Progression ◽  
Single Agent ◽  
Study Drug ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Open Label Study ◽  
Kaplan Meier ◽  
Inhibition Of Angiogenesis ◽  
To Receive

237 Background: HCC is a highly vascularized tumor, and inhibition of angiogenesis by sorafenib (Sor)—a VEGFR and PDGFR inhibitor—delays tumor progression. However, angiogenic escape from Sor may result from activation of the FGFR pathway, which also plays an important role in angiogenesis. Dovitinib (Dov) inhibits FGFR as well as VEGFR and PDGFR. Here, we study frontline Dov vs Sor in pts with advanced HCC. Methods: Eligible pts in this open-label study had ≥ 1 measurable lesion at baseline. All pts were ineligible for or had disease progression after surgical and/or locoregional therapies. Prior systemic HCC therapy was not allowed. Pts were randomized to receive Dov (500 mg/day, 5 days on/2 days off) or Sor (400 mg twice daily) until disease progression, unacceptable toxicity, or death. No treatment crossover was allowed. The primary endpoint was overall survival (OS). The key secondary endpoint was time to tumor progression (TTP) by local investigator’s assessment (per RECIST v1.1). Results: Pts received Dov (n = 82) or Sor (n = 83). Most pts—43 (52.4%) in the Dov arm and 60 (72.3%) in the Sor arm—discontinued treatment due to progressive disease. Median OS (95% CI) was 34.6 wk (28.6-39.4 wk) for Dov and 36.7 wk (23.3-49.3 wk) for Sor; Kaplan-Meier HR, 1.27; 95% CI, 0.89-1.80. Median TTP (95% CI) was 17.6 wk (12.3-18.4 wk) and 17.9 wk (12.3-18.9 wk), respectively. In pts who received ≥ 1 dose of study drug, median duration of exposure was 2.5 mo for Dov (n = 79) and 3.2 mo for Sor (n = 83). The most common adverse events, regardless of cause, were diarrhea (62.0%), decreased appetite (43.0%), nausea and vomiting (40.5% each), fatigue (35.4%), rash (34.2%), and pyrexia (30.4%) in the Dov arm and palmar-plantar erythrodysesthesia syndrome (66.3%), diarrhea (42.2%), and decreased appetite (31.3%) in the Sor arm. VEGFR1 and HGF baseline plasma levels appear to be associated with OS only in the Dov arm. Median OS in the lower biomarker group for both VEGFR1 and HGF was 11 mo while it was 5.6 and 5.9 mo for VEGFR1 and HGF, respectively, in the higher biomarker group. Conclusions: Activity of Dov was not greater than that of Sor in frontline HCC. The safety profile was similar to that observed in other single-agent Dov trials. Clinical trial information: NCT01232296.

[18F] Fluciclatide PET as a biomarker of clinical response to combination therapy of pazopanib and paclitaxel in patients with platinum-resistant or platinum-refractory advanced ovarian cancer: Results of a phase Ib study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3070-3070
Author(s):  
Rohini Sharma ◽  
Pablo Oriol Valls ◽  
Marianna Inglese ◽  
Suraiya Rahim Dubash ◽  
Michelle Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Combination Therapy ◽  
Kinetic Modelling ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Platinum Resistance ◽  
Phase Ib ◽  
Resistant Refractory ◽  
Platinum Resistant ◽  
Pet Tracer

3070 Background: Angiogenesis has been shown to be a driver of platinum resistance in ovarian cancer. We assessed the effect of combination pazopanib and paclitaxel followed by maintenance pazopanib in patients with platinum resistant/refractory ovarian cancer. Integrins αvβ3 and αvβ5 are both up-regulated in tumour-associated vasculature. [18F]Fluciclatide is a novel PET tracer that has high affinity for integrins αvβ3/5, and was used to assess the anti-angiogenic effect of pazopanib. Methods: We conducted an open-label, phase Ib study in patients with platinum resistant/refractory ovarian cancer. Patients received 1 week of single agent pazopanib (800mg daily) followed by combination therapy with weekly paclitaxel 80mg/m2. Following completion of 18 weeks of therapy, patients continued with single agent pazopanib until disease progression. Dynamic [18F]Fluciclatide-PET imaging was conducted at baseline and after 1 week of pazopanib. Response (RECIST 1.1), toxicities and survival outcomes were recorded. Circulating markers of angiogenesis were assessed with therapy. Results: Fourteen patients were included in the intention-to-treat analysis. Complete and partial response was seen in 7 patients (54%). Median progression free survival (PFS) was 7.97 months, and overall survival (OS) was 18.5 months. A reduction in [18F]fluciclatide uptake was observed following 1 week of pazopanib, and the reduction in uptake was predictive of long PFS. Elevated baseline circulating angiopoietin and FGF were predictive of greater reduction in SUV60,mean following pazopanib. Kinetic modelling indicated a reduction in K1 and Ki following pazopanib indicating reduced radiotracer delivery and retention. Conclusions: Combination therapy followed by maintenance pazopanib is effective and tolerable in patients with platinum resistant/refractory ovarian cancer. We have shown that [18F]fluciclatide-PET uptake parameters alter with pazopanib therapy indicating an anti-angiogenic response. Clinical trial information: NCT01608009.

scholarly journals Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial

2020 ◽  
Vol 21 (7) ◽  
pp. 957-968 ◽  
Author(s):  
Panagiotis A Konstantinopoulos ◽  
Su-Chun Cheng ◽  
Andrea E Wahner Hendrickson ◽  
Richard T Penson ◽  
Susan T Schumer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Platinum Resistant

Long-term follow-up of the first randomized study of cisplatin versus carboplatin for advanced epithelial ovarian cancer.

1994 ◽  
Vol 12 (10) ◽  
pp. 2066-2070 ◽  
Author(s):  
A E Taylor ◽  
E Wiltshaw ◽  
M E Gore ◽  
I Fryatt ◽  
C Fisher
Keyword(s):  
Ovarian Cancer ◽  
Single Agent ◽  
Survival Rates ◽  
Advanced Ovarian Cancer ◽  
Phase Iii ◽  
Term Survival ◽  
Gynecology And Obstetrics ◽  
To Receive

PURPOSE A phase III trial was performed between October 1981 and June 1984 to compare the efficacy of single-agent cisplatin and single-agent carboplatin in previously untreated patients with International Federation of Gynecology and Obstetrics stage III or IV carcinoma of the ovary following surgery. This report describes the survival rates of patients in this study after a minimum follow-up duration of 8 years. PATIENTS AND METHODS Sixty-four patients were randomized to receive cisplatin and 67 patients to receive carboplatin. Cisplatin was administered every 4 weeks for a total of 10 courses, courses 1 to 5 at a dosage of 100 mg/m2 and courses 6 to 10 at 30 mg/m2. Carboplatin was administered at a dosage of 400 mg/m2 every 4 weeks for 10 courses. Patients who had clinical or radiologic evidence of response after five courses of chemotherapy underwent second-look surgery. The study was designed to allow crossover between the two arms. Thirteen patients were excluded from response analyses because they were incorrectly randomized. Patients were crossed over to the other arm of the study because of progressive disease (PD), nonresponse, or toxicity. RESULTS The overall response rate for patients randomized to the cisplatin arm was 53.8% (28 of 52; 95% confidence interval [CI], 39% to 68%) and for those randomized to the carboplatin arm, 38.4% (20 of 52; 95% CI, 25% to 53%). There were 16 (30.8%) and 14 (26.9%) complete remissions (CRs) in the cisplatin and carboplatin arms, respectively. None of these differences were statistically significant. The median duration of response for the cisplatin and carboplatin arms was 21 months and 17 months, and the 5-year relapse-free survival rates were 22% and 25%, respectively. The median survival durations for the cisplatin and carboplatin arms were 19.5 and 13 months, and the 5-year survival rates were 15% (95% CI, 8% to 26%) and 19% (95% CI, 11% to 30%), respectively. None of these differences was statistically significant. The median follow-up duration of patients is 9 years. Crossover due to toxicity was more frequent in the cisplatin than the carboplatin arm, occurring in 50% and 3.3% of patients, respectively. CONCLUSION The mature data from this study of patients with advanced ovarian cancer show that cisplatin and carboplatin have similar long-term survival results.

Bevacizumab Combined With Chemotherapy for Platinum-Resistant Recurrent Ovarian Cancer: The AURELIA Open-Label Randomized Phase III Trial

2014 ◽  
Vol 32 (13) ◽  
pp. 1302-1308 ◽  
Author(s):  
Eric Pujade-Lauraine ◽  
Felix Hilpert ◽  
Béatrice Weber ◽  
Alexander Reuss ◽  
Andres Poveda ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Open Label ◽  
Phase Iii Trial ◽  
Platinum Resistant ◽  
Patient Reported ◽  
Single Agent Chemotherapy

Purpose In platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC. Patients and Methods Eligible patients had measurable/assessable OC that had progressed < 6 months after completing platinum-based therapy. Patients with refractory disease, history of bowel obstruction, or > two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes. Results The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients. Conclusion Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.

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