Phase II study of DMXAA combined with carboplatin and paclitaxel in recurrent ovarian cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5032-5032 ◽  
Author(s):  
H. Gabra
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Study ◽  
Objective Response ◽  
Recurrent Ovarian Cancer ◽  
Figo Stage ◽  
Vascular Disrupting Agent ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy

5032 Background: DMXAA (AS1404) is a small-molecule vascular disrupting agent, which in animal models shows additive or supra-additive effects with cytotoxics, including taxanes and platinum agents. This phase II study evaluated DMXAA in combination with carboplatin and paclitaxel in recurrent platinum-sensitive ovarian cancer patients with a progression-free interval of more than 6 months after response to platinum-based chemotherapy. Methods: Patients had first diagnosed disease FIGO stage Ic-IV, with presence of recurrent disease confirmed by imaging. Patients were randomised 1:1 to receive up to 6 cycles of carboplatin (AUC 6 mg/ml × min) and paclitaxel (175 mg/m2) with or without DMXAA (1200 mg/m2). Safety assessments included EKG, adverse events, laboratory screens and ophthalmic exam. Efficacy endpoints are objective response rates, time to progression, duration of response and stable disease, and median and 1-year survival. Results: 55 patients have been enrolled to date from a planned total of ∼70. Initial safety findings in the two arms are comparable. Preliminary investigator-assessed RECIST response data show the following unconfirmed outcomes: of 17 patients in the DMXAA arm, there are 10 with partial responses (PRs), 7 with stable disease (SD) and 0 with progressive disease (PD); of 14 patients in the control arm, there are 8 PRs, 6 SDs and 0 PDs. Conclusions: Initial safety findings suggest that addition of DMXAA to standard doses of carboplatin and paclitaxel did not add significantly to toxicity. Efficacy assessments are ongoing to determine the value of the triple combination in recurrent ovarian cancer. No significant financial relationships to disclose.

Weekly association of gemcitabine and topotecan in early recurrent ovarian cancer patients: A French multicenter phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16016-16016
Author(s):  
F. Joly ◽  
T. Petit ◽  
P. Pautier ◽  
E. Guardiola ◽  
F. Mayer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Survival Time ◽  
Phase Ii ◽  
Stable Disease ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Recurrent Ovarian Cancer ◽  
First Line ◽  
Multicenter Phase

16016 Background: A weekly association of gemcitabine and topotecan was tested with the aim of evaluating its efficacy and tolerance in patients recurring after first line platinum and taxane-based chemotherapy. Methods: From December 2004 to April 2006, 77 patients whose disease has progressed within 12 months (time-free interval, TFI) after first line chemotherapy were enrolled in a multicenter phase II study. Primary endpoint was overall response rate (ORR). Gemcitabine (1000 mg/m2) and topotecan (2.5 mg/m2) were given day 1, 8 and 15 (q 28 d) for 6 to 9 cycles. Tumor response was assessed according to RECIST or Rustin criteria. Clinical response was assessed using symptoms improvement in responders and patients with stable disease. Follow-up was updated December 2006. Results: Initial characteristics were: median age 63 years (38 to 80), WHO PS 0–1 93%, serous histology 85%, TFI < 6 months 45%, measurable disease 71%. Four cycles (1 to 8) were administered in average. The only major toxicity was neutropenia (Grade 3 and 4 in 17% and 6% of patients) with one febrile neutropenia; one toxic death (pneumopathy) was observed. 34% of cycles were incomplete (d8 and/or d15 not administered) because of grade 1–2 thrombopenia or grade 1–4 neutropenia. Lenograstim and erythropoietin were administered in 14% and 34% of patients, respectively. Sixty-six (86%) patients were evaluable for response (2 cycles administered). The ORR was 14% (CR=3%, PR=11%); there were 53% of stable disease. ORR was 7% and 20% in patients with TFI < 6 months and = 6 months, respectively. Symptoms were improved in 18 (64%) of 28 patients and pain in 11 (39%) of 28 patients. Median event-free survival time was 3.7 months. Median overall survival time was 12.3 months (7.5 and 15.6 months in patients with TFI < 6 months and = 6 months, respectively; p=0.0244). Conclusions: In resistant/refractory ovarian cancer, weekly gemcitabine and topotecan is associated with low objective response rate but with a high proportion of stable disease and symptoms control leading to acceptable quality of life. No significant financial relationships to disclose.

OPSALIN: A phase II placebo-controlled randomized study of ombrabulin in patients with platinum-sensitive recurrent ovarian cancer treated with carboplatin (Cb) and paclitaxel (P).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS5112-TPS5112
Author(s):  
Eric Pujade-Lauraine ◽  
Ignace B. Vergote ◽  
Aurore Allard ◽  
Augustin A. Rey ◽  
Cristiana Sessa ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Randomized Study ◽  
Recurrent Ovarian Cancer ◽  
Disease Recurrence ◽  
Prior History ◽  
Vascular Disrupting Agent ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy

TPS5112 Background: Most women with ovarian cancer have disease recurrence after responding to their first treatment with platinum-based chemotherapy and are considered to have platinum-sensitive disease if the relapse-free period is more than 6 months. Although CbP is standard first-line chemotherapy for ovarian cancer, patients with platinum-sensitive recurrent disease are often retreated with CbP. Ombrabulin (AVE8062) is a vascular disrupting agent and analogue of combretastatin A4 that damages established tumor vasculature causing tumor necrosis and has synergistic antitumor activity with platinum agents in tumor models in vivo (Cancer Sci. 2003;94:200). A phase I study showed that treatment with vivo ombrabulin plus CbP is feasible in patients with advanced solid tumors (NCI-AACR-EORTC 2010;Abs 386). We initiated OPSALIN, a phase II randomized trial, to evaluate whether the addition of ombrabulin to CbP improves outcomes in patients with platinum-sensitive recurrent ovarian cancer (NCT01332656; EFC10260). Methods: Eligibility criteria include age of at least 18 years, ECOG PS 0–2, measurable carcinoma of the ovarian epithelium, fallopian tube, or primary peritoneum that is platinum sensitive, and completion of only one previous line of platinum-based chemotherapy. Exclusion criteria include uncontrolled brain metastases, peripheral neuropathy >grade 1, and a prior history of cardiovascular disease. Patients are being randomized (1:1) to receive either ombrabulin 35mg/m2 or placebo plus CbP every 3 weeks. Assigned treatment will continue until disease progression or death, unacceptable toxicity, or consent withdrawal. The primary endpoint is progression-free survival stratified by the time of first disease recurrence (6–12 months or >12 months). Secondary endpoints include safety, response rate, overall survival, pharmacokinetics, and analysis of predictive/prognostic biomarkers. Planned randomization is a total of 150 patients at approximately 45 sites globally. Sixty-five patients have been randomized as of January 2012.

Phase II study of oxaliplatin (OXA) and docetaxel (DTX) in recurrent ovarian cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5086-5086
Author(s):  
G. Ferrandina ◽  
M. Ludovisi ◽  
G. D’Agostino ◽  
A. Naldini ◽  
D. Lorusso ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Median Duration ◽  
Phase Ii Study ◽  
Stage Iv ◽  
Recurrent Ovarian Cancer ◽  
Figo Stage ◽  
Platinum Sensitive ◽  
Grade 3

5086 Background: We conducted a phase II study to evaluate the efficacy and safety of OXA and DTX in recurrent platinum-sensitive ovarian cancer patients. Methods: Patients received DTX 75 mg/m2 (60-min i.v.) on day 1, followed by OXA 100 mg/ m2 (120-min i.v.) on day 1 every 21 days. Results: Between October 2002 and November 2005, 30 Caucasian patients (median age: 53.5 yrs; range, 31–73) were enrolled; 7 (23.3%) patients had FIGO stage I-II disease, 22 (73.3%) had FIGO stage III, and 1 (3.3%) had FIGO stage IV disease. Sites of relapse were as follows: abdominal 3 (10.0%), pelvis 5 (16.7%), lymph nodes 10 (33.3%), peritoneal 7 (23.3%), lung 1 (3.3%), and mixed 4 (13.3%). The median PFI was 28.5 months (range 13–91). The median CA125 was 182 U/ml (range 21–5,596 U/ml). Of the 30 patients evaluable, 13 (43.3%) had complete responses and 7 (23.3%) had partial responses, for an overall response rate of 66.6%. The median time to response was 9.5 wks (range 5–32) and the median duration of response was 43 wks (range 5–124). 8 (26.7%) patients had stable disease (median duration of stabilization: 26.5 wks, range 12–43). 2 (6.7%) patients progressed while on treatment. An overall clinical benefit was observed in 93.3% of patients. All patients were evaluable for toxicity. A total of 186 courses were given, with a median of 6 cycles per patient (range 2–11). Severe toxicities (Grade 3–4 NCI-CTC) included: neutropenia in 29.4% of cycles; severe anemia and thrombocytopenia were not observed. Grade 3–4 neurotoxicity and alopecia were detected in 2.8% and 22.8% of cycles respectively. Allergic reaction was observed only in one case. Doses were reduced by 20% in 14.0% of cycles. Conclusions: In recurrent platinum-sensitive ovarian cancer patients the OXA/DTX combination is highly active with acceptable toxicity, thus making it an attractive regimen. No significant financial relationships to disclose.

A phase I/II study of the vascular disrupting agent BNC105P in combination with gemcitabine-carboplatin in partially platinum-sensitive ovarian cancer patients in first or second relapse: An international collaborative group trial of ANZGOG and HOG.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5612-TPS5612
Author(s):  
Danny Rischin ◽  
Daniela Matei ◽  
Jeffrey C. Goh ◽  
Michelle Margaret Vaughan ◽  
Philip James Beale ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Objective Response ◽  
Collaborative Group ◽  
Synergistic Activity ◽  
Vascular Disrupting Agent ◽  
Platinum Based Chemotherapy ◽  
Vascular Disrupting

TPS5612 Background: BNC105P is a tubulin polymerization inhibitor and a vascular disrupting agent (VDA). In vivo exposure to BNC105P leads to selective damage of tumor vasculature in both primary and metastatic lesions, causing disruption of blood flow to tumors, hypoxia, and associated tumor necrosis. BNC105P also has a direct anti-proliferative action on cancer cells, including ovarian cancer cell lines. Pre-clinical data has demonstrated synergistic activity of BNC105P when combined with platinum or with gemcitabine, supporting the proposed study design. This study will determine the safety and efficacy of BNC105P in ovarian cancer when used in combination with gemcitabine-carboplatin. The target population is women with ovarian or primary peritoneal cancers who progressed 4 to 9 months after first-line platinum based chemotherapy, or 4 to 12 months after second line platinum based chemotherapy. Methods: A single arm phase I will be used to determine the phase II dose for the triplet combination (3-6 subjects per dose level, maximum of 24 subjects). Four dose levels of BNC105P (12-16 mg/m2) and gemcitabine (800-1000 mg/m2) will be assessed. The dose of carboplatin will be set at AUC 4. Enrolment to cohort 2 started in January 2013. The phase II component will consist of a 2-arm, randomized (1:1) study of BNC105P, gemcitabine and carboplatin versus gemcitabine and carboplatin alone. The primary endpoint for the phase II trial is objective response rate (ORR, according to RECIST 1.1 and/or GCIG CA125 criteria. An ORR of 40% or more with the experimental regimen would be considered worthy of further investigation, assuming an ORR of 20% with the control regimen. 110 phase II participants are planned (N = 55/arm). Treatment allocation will be balanced using minimization for the study site, target lesions according to RECIST (present vs. absent), progression free interval from last platinum based chemotherapy regimen (<6 months vs 6 months or more), and first relapse vs. second relapse. Biomarker (tissue and blood-borne) sampling and PK analysis will also be undertaken. Clinical trial information: NCT01624493.

A phase II study of gemcitabine, carboplatin and bevacizumab for the treatment of platinum-sensitive recurrent ovarian cancer

2014 ◽  
Vol 134 (2) ◽  
pp. 262-266 ◽  
Author(s):  
Eric L. Eisenhauer ◽  
Vanna Zanagnolo ◽  
David E. Cohn ◽  
Ritu Salani ◽  
David M. O'Malley ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Recurrent Ovarian Cancer ◽  
Platinum Sensitive

A phase II study of gemcitabine, carboplatin and bevacizumab for the treatment of platinum-sensitive recurrent ovarian cancer

2011 ◽  
Vol 120 ◽  
pp. S31
Author(s):  
E. Eisenhauer ◽  
V. Zanagnolo ◽  
D. Cohn ◽  
R. Salani ◽  
D. O'Malley ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Recurrent Ovarian Cancer ◽  
Platinum Sensitive

scholarly journals Docetaxel and oxaliplatin in the second-line treatment of platinum-sensitive recurrent ovarian cancer: a phase II study

2007 ◽  
Vol 18 (8) ◽  
pp. 1348-1353 ◽  
Author(s):  
G Ferrandina ◽  
M Ludovisi ◽  
R De Vincenzo ◽  
V Salutari ◽  
D Lorusso ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Recurrent Ovarian Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Platinum Sensitive

Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study

2021 ◽  
pp. JCO.21.00605
Author(s):  
Oliver Zivanovic ◽  
Dennis S. Chi ◽  
Qin Zhou ◽  
Alexia Iasonos ◽  
Jason A. Konner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Intraperitoneal Chemotherapy ◽  
Cytoreductive Surgery ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Phase Ii Study ◽  
Recurrent Ovarian Cancer ◽  
Hazard Ratio ◽  
Platinum Sensitive ◽  
Secondary Cytoreductive Surgery

PURPOSE The purpose of this phase II study was to evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin for recurrent ovarian cancer during secondary cytoreductive surgery. MATERIALS AND METHODS Patients were intraoperatively randomly assigned to carboplatin HIPEC (800 mg/m2 for 90 minutes) or no HIPEC, followed by five or six cycles of postoperative IV carboplatin-based chemotherapy, respectively. Based on a binomial single-stage pick-the-winner design, an arm was considered winner if ≥ 17 of 49 patients were without disease progression at 24 months post-surgery. Secondary objectives included postoperative toxicity and HIPEC pharmacokinetics. RESULTS Of 98 patients, 49 (50%) received HIPEC. Complete gross resection was achieved in 82% of the HIPEC patients and 94% of the standard-arm patients. Bowel resection was performed in 37% of patients in the HIPEC arm compared with 65% in the standard ( P = .008). There was no perioperative mortality and no difference in use of ostomies, length of stay, or postoperative toxicity. At 24 months, eight patients (16.3%; 1-sided 90% CI, 9.7 to 100) were without progression or death in the HIPEC arm and 12 (24.5%; 1-sided 90% CI, 16.5 to 100) in the standard arm. With a medium follow-up of 39.5 months, 82 patients progressed and 37 died. The median progression-free survival in the HIPEC and standard arms were 12.3 and 15.7 months, respectively (hazard ratio, 1.54; 95% CI, 1 to 2.37; P = .05). There was no significant difference in median overall survival (52.5 v 59.7 months, respectively; hazard ratio, 1.39; 95% CI, 0.73 to 2.67; P = .31). These analyses were exploratory. CONCLUSION HIPEC with carboplatin was well tolerated but did not result in superior clinical outcomes. This study does not support the use of HIPEC with carboplatin during secondary cytoreductive surgery for platinum-sensitive recurrent ovarian cancer.

Phase II study of trabectedin in pretreated patients with recurrent epithelial ovarian cancer (REOC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5559-5559
Author(s):  
Marco Marinaccio ◽  
Emilia Mele ◽  
Vito Lorusso ◽  
Valeria Vincenza Fumarulo ◽  
Fausta Sozzi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Partial Response ◽  
Epithelial Ovarian Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Study ◽  
Single Agent ◽  
Objective Response ◽  
Response To Treatment ◽  
Open Label

5559 Background: The prognosis of patients with REOC is extremely poor after several lines of chemotherapy. The choice and timing of therapies must be individualized to optimize survival and quality of life. This open-label, nonrandomized, phase II study was aimed at evaluating efficacy and toxicity of Trabectedin as a single-agent therapy in patients with preteated Recurrent Epithelial Ovarian Cancer (REOC). Methods: Sixteen patients (median age 51 yrs, range 44 – 71) with REOC who progressed after 2 (18.7%), 3 (56.3%) or 4 (25.0%) previous lines of chemotherapy were treated with Trabectedin at the dose of 1.1 mg/m2 via a 3-hour i.v. infusion with dexamethasone pretreatment every 3 weeks until disease progression, unacceptable toxicity or when a stability of disease was reached. Clinical objective response was the primary efficacy endpoint; the secondary one was safety. Response to treatment was assessed according to Response Evaluation Criteria in Solid Tumours (RECIST, version 1.1), and toxicities were graded according to NCI Common Toxicity Criteria, version 2.0. Results: The median number of treatment cycles per patients was 5 (range, 2-9 cycles). A total of 81 cycles were administered. A dose reduction was never required. Main toxicities included anemia (20.9%), leucopenia (15.0%), thrombocytopenia (4.5%) and asthenia (22.2%). No deaths were attributable to therapy. No one showed complete response, while 9/16 partial response (56.2%) and 4/16 stable disease (25.0%) were observed. 3/19 pts (18.8%) progressed on therapy. The median progression-free interval was 18 weeks in patients with partial response; stable disease was maintained for a median time of 12 weeks. Conclusions: Trabectedin 1.1mg/m2 given as a 3-hour i.v. infusion every 3 weeks was well tolerated and has confirmed a very interesting antitumor activity in this heavily pretreated population and it seems also to be a very tolerable regimen. The co-treatment with dexamethasone improves the safety of Trabectedin by reducing drug-induced myelosuppression and hepatotoxicity. Trabectedin has a manageable toxicity profile, and can be safely administered thanks to its secure action profile also in patients with no other viable therapeutic options.

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