A phase II study of intravenous (IV) and intraperitoneal (IP) paclitaxel (Tax), IP cisplatin (Cis), and IV bevacizumab (Bev) as first-line chemotherapy for optimal stage II or III ovarian, primary peritoneal, and fallopian tube cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5523-5523 ◽  
Author(s):  
J. A. Konner ◽  
K. Fallon ◽  
S. Pezzuli ◽  
A. Iasonos ◽  
P. Sabbatini ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Abdominal Pain ◽  
Fallopian Tube ◽  
Phase Ii ◽  
Recurrent Ovarian Cancer ◽  
Stage Ii ◽  
Phase Ii Trials ◽  
Fallopian Tube Cancer ◽  
Peritoneal Cancer ◽  
Grade 3

5523 Background: IP Cis plus IV/IP Tax is a standard therapy for optimally debulked ovarian cancer. Bev is a recombinant humanized IgG1 monoclonal antibody directed against vascular endothelial growth factor (VEGF). Activity of Bev against recurrent ovarian cancer has been reported in phase II trials. In this study IP Cis and IV/IP Tax are combined with IV Bev as front-line therapy to assess safety and tolerability. Methods: Patients with optimal (<1 cm residual), FIGO stage II or III, epithelial ovarian, fallopian tube, or peritoneal cancer, acceptable organ function, and KPS = 70% are eligible. Patients receive 6 cycles of chemotherapy plus Bev (starting cycle 2): Tax 135 mg/m2 IV over 3 hours on Day 1, Cis 75 mg/m2 IP on Day 2, Tax 60 mg/m2 IP on Day 8, Bev 15 mg/kg IV on Day 1. Extended treatment with Bev is continued every 3 weeks for 17 treatments after chemotherapy is complete. The study will enroll 41 patients. The primary endpoint is safety and tolerability, determined by the proportion of patients who complete the prescribed 6 cycles of cytotoxic chemotherapy without discontinuation and without dose-limiting non-hematologic and non-electrolyte toxicity. A stopping rule will be applied if excessive toxicity is encountered. Results: To date, 8 women have been treated on the study. Median age: 53 (48–59). All 31 planned doses of chemotherapy have been administered in full. One dose of IP Tax was delayed for 2 days due to abdominal pain. One patient had her first dose of Bev delayed for 1 cycle due to surgical wound infection. There have been no toxicities > grade 3. Grade 1/2 toxicities include: fatigue (87.5%); nausea (50%); and hypomagnesemia (37.5%). Grade 3 toxicities per patient: fatigue (12.5%); hyponatremia (25%); hypokalemia (25%); hypertension (12.5%); abdominal pain (12.5%); and neutropenia (12.5%). Of the 5 patients with pretreatment CA125 >35 Units/mL, 4 normalized their value after 1 cycle of chemotherapy and 1 patient normalized after 2 cycles. Conclusions: Preliminary experience suggests that the combination of IV Bev with IP Cis plus IV/IP Tax may be well tolerated. Enrollment continues and updated results will be presented. No significant financial relationships to disclose.

A phase II study of intravenous (IV) and intraperitoneal (IP) paclitaxel, IP cisplatin, and IV bevacizumab as first-line chemotherapy for optimal stage II or III ovarian, primary peritoneal, and fallopian tube cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5539-5539 ◽  
Author(s):  
J. A. Konner ◽  
D. Grabon ◽  
S. Pezzulli ◽  
A. Iasonos ◽  
P. Sabbatini ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Small Bowel ◽  
Fallopian Tube ◽  
Phase Ii ◽  
Anastomotic Dehiscence ◽  
Stage Ii ◽  
Phase Ii Trials ◽  
Fallopian Tube Cancer ◽  
Peritoneal Cancer ◽  
Grade 3

5539 Background: IP cisplatin (Cis) plus IV/IP paclitaxel (Tax) is a standard therapy for optimally debulked ovarian cancer. Bevacizumab (Bev) is a recombinant humanized IgG1 monoclonal antibody directed against vascular endothelial growth factor. Activity of Bev in recurrent ovarian cancer has been reported in phase II trials. In this study IP Cis and IV/IP Tax are combined with IV Bev as front-line therapy. Methods: Patients with optimal (<1 cm residual), FIGO stage II or III, epithelial ovarian, fallopian tube, or peritoneal cancer, acceptable organ function, and KPS ≥ 70% are eligible. Patients receive 6 cycles of chemotherapy plus Bev: Tax 135 mg/m2 IV over 3 hours on Day 1, Cis 75 mg/m2 IP on Day 2, Tax 60 mg/m2 IP on Day 8, Bev 15 mg/kg IV on Day 1 (starting cycle 2). Bev is continued every 3 weeks for 17 treatments after chemotherapy is complete. This study will enroll 41 patients. The primary endpoint is safety and tolerability, determined by whether at least 60% of patients complete the prescribed 6 cycles of cytotoxic chemotherapy without unacceptable toxicity. Results: Thirty-nine women [median age 56 (40–69)] have been treated on study: 26 (67%) completed 6 IV/IP cycles; 5 (13%) are receiving ongoing IV/IP treatment; 4 (10%) experienced IP port malfunction (3 finished 5 IV/IP cycles, 1 came off study for port revision); 3 (8%) switched from IP Cis to IV carboplatin due to grade 3 nephrotoxicity in cycle 1 (n = 2) or grade 3 hypertension in cycle 6 (n = 1); and 1 (2.5%) patient died following rectosigmoid anastomotic dehiscence during cycle 4. Grade 3/4 treatment-related toxicities include hypertension (10%), vasovagal events (10%), neutropenia (26%), nausea/vomiting (10%), and hypomagnesemia (8%). There were 3 occurrences of grade 3 abdominal pain (8%); and 3 adhesion-related grade 3 small bowel obstructions (8%), during cycles 3, 9, and 15, respectively. Conclusions: The addition of Bev to this IV/IP regimen appears to be feasible. Bev may increase the risk of small bowel obstruction/perforation in these patients. Enrollment continues and updated results will be presented. [Table: see text]

Phase II trial of bevacizumab and pemetrexed for recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5013-5013 ◽  
Author(s):  
Andrea R. Hagemann ◽  
Israel Zighelboim ◽  
Akiva Pesach Novetsky ◽  
Feng Gao ◽  
L. Stewart Massad ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Phase Ii ◽  
Objective Response ◽  
Recurrent Ovarian Cancer ◽  
Phase Iii ◽  
Ca 125 ◽  
Peritoneal Cancer ◽  
Platinum Sensitive ◽  
Vegf Inhibitor ◽  
Grade 3

5013 Background: This phase II clinical trial evaluated the efficacy and safety of the combination of bevacizumab, a VEGF inhibitor, and pemetrexed, a multi-targeted antifolate agent inhibiting thymidylate synthase, for recurrent or persistent epithelial ovarian, fallopian tube (FT) or primary peritoneal (PP) cancer. Methods: Patients with measurable recurrent/persistent epithelial ovarian, FT or PP cancer after at least one prior platinum- and taxane-containing regimen were eligible. Patients might have received < 2 prior cytotoxic chemotherapy regimens but no prior bevacizumab. Pemetrexed 500 mg/m2 IV and bevacizumab 15 mg/kg IV were given every 3 weeks until progression, unacceptable adverse effects, or patient/physician choice. 32 patients were needed to have 90% power to detect the primary endpoint of 6-month PFS ≥ 40% with a two-sided 0.05 significance. Secondary endpoints included toxicity and response by RECIST and CA-125 criteria. Results: Thirty-four patients received a median of 7 treatment cycles (range, 2-26). Twenty-eight patients (82%, 95% CI: 66-92) were platinum-sensitive. Median follow-up was 17.1 months (range, 2.7-31.2). The 6-month PFS was 58.2% (95%CI: 40-73) for all patients and 50% (19-81) for platinum-resistant patients. Objective response rates by RECIST criteria included (%; 95%CI): 0 CR, 14 PR (41%; 25-59), 18 SD (53%; 35-70) and 2 PD (6%; 1-20). Of 27 patients evaluable by CA-125, levels declined ≥50% in 17 (62%; 44-79), and ≥75% in 8 (30%; 16-49). 12-month OS was 88% (95%CI: 71-95) and median PFS was 7.8 months (95%CI: 4.7-10.7). Of the 34 patients, grade 3-4 hematologic toxicities occurred in 53% (neutropenia 50%, leukopenia 26%, thrombocytopenia 12%, anemia 9%). Other grade 3-4 toxicities included metabolic (29%), constitutional (18%), pain (18%) and gastrointestinal (15%). No bowel perforations occurred. Conclusions: Combined bevacizumab/pemetrexed is well tolerated and highly active for the treatment of recurrent ovarian cancer. The dose and schedule tested here warrant further investigation in phase III trials.

A phase II trial of enzalutamide in patients with androgen receptor positive (AR+) ovarian, primary peritoneal or fallopian tube cancer and one, two, or three prior therapies.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS5610-TPS5610 ◽  
Author(s):  
Rachel N. Grisham ◽  
Dilip D. Giri ◽  
Alexia Iasonos ◽  
Qin Zhou ◽  
Jeffrey Girshman ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Androgen Receptor ◽  
Fallopian Tube ◽  
Phase Ii ◽  
Serum Testosterone ◽  
Cancer Center ◽  
Fallopian Tube Cancer ◽  
Peritoneal Cancer ◽  
Androgen Receptor Antagonist ◽  
Recist 1.1

TPS5610 Background: Approximately 75% of women with epithelial ovarian cancer (OC) present with advanced disease. Most of these women will ultimately recur and require life-long treatment for their cancer. Well tolerated therapies for treatment in the recurrent setting are needed. The AR is expressed in greater than 60% of cases of OC and is more prevalent than the estrogen or progesterone receptor. All past clinical studies of AR inhibition in OC have focused on unselected populations of heavily pretreated women; however preclinical data suggests that AR expression decreases in OC cells with increasing lines of therapy. Enzalutamide is a small molecule androgen receptor-antagonist that is FDA approved for treatment of prostate cancer and is currently being investigated as treatment for breast and ovarian cancer. Methods: This is a phase II, single-institution trial of enzalutamide 160mg po QD in patients with AR+ ovarian, fallopian tube or primary peritoneal cancer. Eligible patients must be found to have greater than or equal to 5% AR staining by IHC on FFPE tumor tissue and been treated with only 1,2 or 3 prior cytotoxic therapies. Patients must have RECIST 1.1 defined measurable disease. Enrolled patients are treated with enzalutamide until progression of disease or unacceptable toxicity. The primary endpoint is to estimate the proportion of women who achieve a complete or partial response by RECIST 1.1 criteria or survive progression free for at least 6 months. Secondary objectives include the retrieval of optional tumor biopsies at time of progression to evaluate the effect of enzalutamide on AR expression and to observe the effect of enzalutamide on serum testosterone and estradiol levels. This study will enroll 58 patients at Memorial Sloan Kettering Cancer Center and its regional sites. The study utilizes a safety lead-in phase and a two-stage design. The first patient enrolled in April 2015. The safety lead-in phase has been completed. The prespecified activity goal for the first stage was met; second stage accrual began in October 2016. Thus far, 35 patients have initiated treatment. Clinical trial information: NCT01974765.

Responses to second-line cisplatin-based intraperitoneal therapy in ovarian cancer: influence of a prior response to intravenous cisplatin.

1991 ◽  
Vol 9 (10) ◽  
pp. 1801-1805 ◽  
Author(s):  
M Markman ◽  
B Reichman ◽  
T Hakes ◽  
W Jones ◽  
J L Lewis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Small Volume ◽  
Recurrent Ovarian Cancer ◽  
Second Line ◽  
Front Line ◽  
Phase Ii Trials ◽  
Two Phase ◽  
Overall Response ◽  
Intraperitoneal Therapy

Phase II trials of second-line intraperitoneal (IP) cisplatin-based therapy in patients with ovarian cancer have demonstrated the ability of this approach to produce objective antitumor responses, including surgically defined complete responses (CRs), in individuals with persistent small-volume disease after front-line cisplatin-based intravenous (IV) treatment. To examine the influence of a prior response to systemic cisplatin on the activity of second-line IP cisplatin, we retrospectively analyzed two phase II trials of cisplatin-based IP therapy in persistent/recurrent ovarian cancer conducted at our institution. Of the 89 assessable patients on the two trials, 52 (58%) had previously responded to IV cisplatin. The overall response and CR rates to second-line IP cisplatin-based therapy in this previously responding population were 56% and 33%, respectively, compared with overall response and CR rates in the 37 nonresponders to IV cisplatin of 11% and 3%, respectively (P less than .001; chi 2, 1 df). In the 36 patients responding to systemic cisplatin and whose largest tumor mass measured less than 1 cm at IP cisplatin initiation, a 42% CR rate was observed, compared with a 7% CR rate in the 14 patients with the same bulk of disease who had previously failed to respond to systemic cisplatin (P less than .025). We conclude that a prior response to systemic cisplatin strongly influences the antineoplastic activity of second-line IP cisplatin in ovarian cancer.

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