Randomized, Phase II, Placebo-Controlled, Double-Blind Study With and Without Enzastaurin in Combination With Paclitaxel and Carboplatin As First-Line Treatment Followed by Maintenance Treatment in Advanced Ovarian Cancer

2013 ◽  
Vol 31 (25) ◽  
pp. 3127-3132 ◽  
Author(s):  
Ignace B. Vergote ◽  
Radoslav Chekerov ◽  
Frederic Amant ◽  
Philipp Harter ◽  
Antonio Casado ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Translational Research ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Controlled Study ◽  
Double Blind Study ◽  
Double Blind ◽  
Gynecology And Obstetrics

Purpose Enzastaurin is an oral serine/threonine kinase inhibitor antitumor agent. Our phase II trial tested the efficacy and safety of enzastaurin added to a standard carboplatin/paclitaxel chemotherapy regimen in patients with newly diagnosed advanced ovarian cancer. Patients and Methods This was a randomized, placebo-controlled study in patients with International Federation of Gynecology and Obstetrics stage IIB to IV ovarian, fallopian tube, or peritoneal epithelial carcinoma. Patients were randomly assigned to six cycles of chemotherapy (paclitaxel/carboplatin ± enzastaurin [PCE/PC]) followed by maintenance therapy (enzastaurin/placebo). Primary end point was progression-free survival (PFS). Secondary measures included response rate, safety assessment, and translational research. Results A total of 142 patients were randomly assigned to PCE (n = 69) or PC (n = 73). Patients in the PCE group had a 3.7-month longer median PFS compared with patients in the PC group; this was not statistically significant (hazard ratio [HR], 0.80; 95% CI, 0.50 to 1.29; P = .37). Safety profiles of the treatment arms were comparable. Frequency of discontinuation because of adverse events was similar (PCE, 11.9%; PC, 9.7%). Multivariate analyses confirmed the importance of optimal debulking with regard to PFS (debulking optimal v suboptimal: HR, 0.51; 95% CI, 0.30 to 0.85; P = .009). HR for covariate stage (stage IIB to IIIB v IIIC to IV) was not statistically significant (0.75; 95% CI, 0.38 to 1.47; P = .40). Translational research of immunohistochemistry protein assays did not identify any markers significantly associated with treatment difference regarding PFS. Conclusion The PCE combination increased PFS, but it was not significantly superior to PC in this phase II study.

INTEGRATE: A randomized phase II double-blind placebo-controlled study of regorafenib in refractory advanced oesophagogastric cancer (AOGC)—A study by the Australasian Gastrointestinal Trials Group (AGITG), first results.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 9-9 ◽  
Author(s):  
Nick Pavlakis ◽  
Katrin Marie Sjoquist ◽  
Eric Tsobanis ◽  
Andrew Martin ◽  
Yoon-Koo Kang ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitor ◽  
Secondary Analysis ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Prognostic Indicators ◽  
Controlled Study ◽  
Primary Analysis ◽  
Double Blind

9 Background: Advanced Oesophago-Gastric Carcinoma (AOGC) has limited options following failure of first or second line chemotherapy (CT). Regorafenib (REG) is an oral multi-kinase inhibitor of kinases involved in angiogenesis, tumor microenvironment, and oncogenesis. This study examined whether REG has sufficient activity and safety for further evaluation. Methods: International (Australia & New Zealand (ANZ), Korea, Canada (NCIC CTG)) randomised phase II trial with 2:1 randomisation and stratification by: (1) Lines of prior CT for advanced disease (1 vs. 2) and (2) Region. Eligible patients received best supportive care plus 160mg REG or matching PBO orally on days 1-21 each 28-day cycle until disease progression or prohibitive adverse events. Primary endpoint was progression free survival (PFS) in the REG arm, assuming median 8 weeks (wks) in PBO arm, aiming for 13.2 wks with REG to be of interest. Results: From Nov 2012 to Feb 2014, 152 patients were enrolled, 147 evaluable [pre-specified primary analysis population]: (REG n=97: PBO n=50); well matched for key baseline prognostic indicators; male:female (118:29); primary location: OG Junction (56), stomach (85); lines of prior therapy: 1 (63), 2 (84); ECOG 0 (62): 1 (85). Time on treatment: Median: 7.9 (REG) v 4 (PBO) wks. In the evaluable population median PFS was 11.1 wks (95% CI: 7.7 - 12.3) (REG) and 3.9 wks (95% CI: 3.7 - 4.0) (PBO), log-rank p <0.0001; HR 0.41 (95% CI: 0.28 to 0.59). PFS results were maintained for secondary analysis including all randomized patients (n = 152). REG was well tolerated, with the spectrum of toxicity in keeping with previous reports. Conclusions: PFS was clearly significantly longer with REG than PBO, though PBO PFS was less than anticipated. The pre-specified exploratory comparisons provide compelling evidence that REG has sufficient activity with acceptable tolerability in refractory AOGC to warrant phase III evaluation. Mature OS results will be presented at the meeting. Clinical trial information: 12612000239864.

scholarly journals Successful treatment of advanced ovarian cancer with anlotinib: a case report

2020 ◽  
Vol 48 (12) ◽  
pp. 030006052097682
Author(s):  
Ping Zhang ◽  
Liangliang Ma ◽  
Xiaojie Wang ◽  
Ruijie Zhang ◽  
Yuting Dong
Keyword(s):  
Ovarian Cancer ◽  
Mild Hypertension ◽  
Kinase Inhibitor ◽  
Therapeutic Option ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Inhibit Tumor Growth ◽  
Free Survival ◽  
Multiple Line ◽  
Serum Ca125

Ovarian cancer remains the most lethal gynecological malignant tumor, with relapse occurring in approximately 70% of advanced cases. Anlotinib is an oral small-molecule multi-targeted tyrosine kinase inhibitor that can resist neoangiogenesis and inhibit tumor growth. Previous research demonstrated clinical antitumor activity of anlotinib in various cancers. We report the case of an elderly woman with advanced ovarian cancer who received anlotinib after failure of multiple-line chemotherapy. A partial response was observed after six cycles of anlotinib monotherapy, with a reduction in the size of the metastases and significantly decreased serum CA125 levels from 1832.7 U/mL to 118.7 U/mL. She continued to take anlotinib, with a progression-free survival time of more than 4 months. Only mild hypertension was observed during the treatment. Anlotinib monotherapy may be a novel therapeutic option for patients with advanced ovarian cancer.

Chemotherapy of advanced ovarian cancer with 4'-O-tetrahydropyranyl doxorubicin and cisplatin: a randomized phase II trial with an evaluation of circadian timing and dose-intensity.

1990 ◽  
Vol 8 (4) ◽  
pp. 705-714 ◽  
Author(s):  
F Lévi ◽  
M Benavides ◽  
C Chevelle ◽  
F Le Saunier ◽  
F Bailleul ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Experimental Studies ◽  
Advanced Ovarian Cancer ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Clinical Response Rate ◽  
Survival Times ◽  
Gynecology And Obstetrics ◽  
Pathological Cr

The efficacy and toxicity of the new anthracycline, 4'-0-tetrahydropyranyl doxorubicin (THP) (50 mg/m2 intravenous [IV] bolus) in association with cisplatin (100 mg/m2 IV as a 4-hour infusion) was assessed in 31 patients with advanced ovarian carcinoma. Twenty-eight patients were assessable for toxicity among whom 25 were assessable for response (International Federation of Gynecology and Obstetrics [FIGO] stage IIIa, four patients; IIIb, 15 patients; IV, six patients). Nine patients had received prior treatment. Patients were randomized to receive schedule (sch) A (THP at 6 hours, then cisplatin from 16 to 20 hours) or sch B (THP at 18 hours, then cisplatin from 4 to 8 hours). Sch A was hypothesized as less toxic since THP was best tolerated in the late rest span and cisplatin near the middle of the activity span in experimental studies. The rate of clinical complete response (CR) was 52%, that of partial response (PR) was 12%, and the overall clinical response rate (CR plus PR) was 64% (sch A, 73%; sch B, 57%). Median progression-free survival and survival times were, respectively, 10 and 19 months. Of 12 patients in clinical CR evaluated at second-look laparotomy, four had a pathological CR (33%), and three had microscopic residual disease (MD). The overall rate of pathological CR was 16%. Sch A was associated with less neutropenia (P = .10), thrombocytopenia (P less than .01), anemia (P less than .01), and renal toxicity (P less than .05) than sch B. Of four patients withdrawn for toxicity, three were on sch B (one death). Mean dose intensities (DIs) of THP and cisplatin, respectively, decreased by 30% and 47% over the five initial courses. Such decrease was significantly more pronounced for sch B than for sch A in previously untreated patients (P from 2-way analysis of variance [ANOVA] less than .01). THP-cisplatin is active against advanced ovarian cancer, and its toxicities can be significantly decreased by dosing THP in the early morning and cisplatin in the late afternoon as compared with THP in the evening and cisplatin the next morning.

A randomized, double-blinded, placebo-controlled, multi-institutional, cross-over, phase II.5 study of saracatinib (AZD0530), a selective Src kinase inhibitor, in patients with recurrent osteosarcoma localized to the lung.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS10591-TPS10591 ◽  
Author(s):  
Kristin Baird ◽  
Denise K. Reinke ◽  
Joseph Gerald Pressey ◽  
Leo Mascarenhas ◽  
Noah Federman ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Treatment Guidelines ◽  
Src Kinase ◽  
Progression Free Survival ◽  
Primary Treatment ◽  
Complete Resection ◽  
Controlled Study ◽  
Complete Surgical Resection

TPS10591 Background: Osteosarcoma is a rare cancer and 33% of patients who have completed primary treatment will recur. The Src pathway has been implicated in the metastatic behavior of several tumors including osteosarcoma where 95% of samples express Src or have evidence of downstream activation of this pathway. Saracatinib (AZD0530) is a potent and selective Src kinase inhibitor. The recommended phase II dose in adults was found to be 175mg daily. The primary goal of this study is to determine if treatment with Saracatinib can increase progression free survival (PFS) for patients who have undergone complete resection of metastatic osteosarcoma nodules in the lung. Secondary goals are evaluation of overall survival, time to treatment failure, and evaluation of several biological correlatives. Methods: This is a multi-institutional, phase II.5, placebo-controlled study with an accrual goals of 88 randomized patients. Patients between 15 and 75 years, with histological confirmation of recurrent osteosarcoma, localized to the lung, who have potential for complete surgical resection, are eligible for enrollment. After complete resection, patients are randomized to treatment with saracatinib or placebo, of a daily oral dose of 175 mg, continuously for up to 1 year or until progression. Patients who recur in the lung while on-study and who are amenable to complete surgical resection will be un-blinded. Those patients who received placebo may have the option to undergo surgical resection. If fully resected, they will be offered therapy with saracatinib under the same treatment guidelines as above. As of January 2013, 38 patients have enrolled and 32 patients met the criteria to be randomized and began oral therapy with either saracatinib or placebo. An interim analysis is planned after 40 patients have been randomized. Clinical trial information: NCT00752206.

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