Phase II study of MKC-1 in patients with metastatic or resistant epithelial ovarian cancer or advanced endometrial cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5577-5577 ◽  
Author(s):  
C. Elser ◽  
H. Hirte ◽  
L. Kaizer ◽  
H. Mackay ◽  
S. Bindra ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Endometrial Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Gastrointestinal Disorder ◽  
Ca 125 ◽  
Platinum Resistant ◽  
Parallel Group ◽  
Grade 3

5577 Background: MKC-1 is a novel oral cell cycle inhibitor with preclinical activity in xenograft models of human ovarian and endometrial cancers. MKC-1 also reduces pAKT, an attractive target in endometrial cancer due to frequent PTEN mutations. Methods: The objective of this phase II study is to assess the efficacy of MKC-1 in 2 patient (pt) populations: metastatic or recurrent platinum-resistant ovarian cancer (EOC) and advanced endometrial cancer (EC). Three prior lines of treatment were allowed in both groups. A two arm, parallel group multicenter 2-stage design was used. The primary endpoint was tumor response by RECIST or CA-125. MKC-1 125 mg/m2 was administered orally twice daily for 14 days in 28-day cycles. Results: Accrual to stage one is complete with 21 pts in each arm. 19 pts with EOC (median age 56 yrs, range 31–71) and 9 patients with EC (median 63 range 50–74) were available for efficacy. A total of 66 cycles (EOC/EC: 39/27cycles) median 2 per patient (range 1–8) were delivered. 11/4 pts had prior adjuvant CT, 14/10 had prior systemic CT for advanced disease, and 2/6 received prior radiation. In pts with EOC, 7 pts have stable disease (SD), 12 progressive disease (PD), 2 remain on study. Median time to progression is 1.8 months. In pts with EC 4 pts had SD, 5 PD, 6 remain on study. Toxicity data are available in 28 pts (17/11). Most common adverse events (AE) possibly related to MKC-1 were fatigue, nausea, elevated ALT or AST, urine discoloration, anemia, anorexia, elevated AP and gastrointestinal disorder in 55%, 39%, 36%, 24%, 23%, 21%, 21%, and 21 % of cycles respectively. The only possibly related grade 3+ AEs were neutropenia, leucopenia and hyponatremia in 9 %, 3 %, and 2% of cycles. Conclusions: MKC-1 was well tolerated in both patient populations. Single agent MKC-1 has insufficient activity in platinum resistant EOC to warrant further investigation. Updated clinical data for both patient groups will be presented at the meeting. [Table: see text]

Oxaliplatin or Paclitaxel in Patients With Platinum-Pretreated Advanced Ovarian Cancer: A Randomized Phase II Study of the European Organization for Research and Treatment of Cancer Gynecology Group

2000 ◽  
Vol 18 (6) ◽  
pp. 1193-1202 ◽  
Author(s):  
Martine J. Piccart ◽  
John A. Green ◽  
Angel Jimenez Lacave ◽  
Nick Reed ◽  
Ignace Vergote ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Time To Progression ◽  
European Organization ◽  
Randomized Phase Ii ◽  
Grade 3

PURPOSE: This was a multicentric, open, randomized, phase II study of single-agent paclitaxel and oxaliplatin to evaluate the efficacy of oxaliplatin in a relapsing progressive ovarian cancer patient population and to analyze the safety profile and impact of both agents on quality of life, time to progression, and survival. PATIENTS AND METHODS: Eighty-six patients with platinum-pretreated advanced ovarian cancer were randomly assigned to two arms: 41 received paclitaxel at 175 mg/m2 over 3 hours every 3 weeks, and 45 received oxaliplatin at 130 mg/m2 over 2 hours every 3 weeks. For inclusion, patients had to have a performance status of 0 to 2 and to have received at least one and no more than two prior cisplatin- and/or carboplatin-containing chemotherapy regimens within the last 12 months. RESULTS: Seven confirmed responses were observed in each arm, for an overall response rate in the total treated population of 17% (95% confidence interval [CI], 7% to 32%) in the paclitaxel arm and 16% (95% CI, 7% to 29%) in the oxaliplatin arm. Median time to progression was 14 weeks and 12 weeks, and overall survival was 37 weeks and 42 weeks in the paclitaxel and oxaliplatin arms, respectively. Among 63 patients with a 0- to 6-month progression-free, platinum-free interval, there were five objective responses with paclitaxel in 31 patients and two objective responses with oxaliplatin in 32 patients. Nine patients (22%) in the paclitaxel arm had grade 3 or 4 neutropenia (National Cancer Institute of Canada [NCIC] Common Toxicity Criteria). Two patients (4%) experienced grade 3 thrombocytopenia in the oxaliplatin arm. Maximum grade (grade 3) NCIC neurosensory toxicity was experienced by three patients (7%) in the paclitaxel arm and by four patients (9%) in the oxaliplatin arm. CONCLUSION: Single-agent oxaliplatin at 130 mg/m2 every 3 weeks is active with moderate toxicity in patients with cisplatin-/carboplatin-pretreated advanced ovarian cancer.

Volasertib Versus Chemotherapy in Platinum-Resistant or -Refractory Ovarian Cancer: A Randomized Phase II Groupe des Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire Study

2016 ◽  
Vol 34 (7) ◽  
pp. 706-713 ◽  
Author(s):  
Eric Pujade-Lauraine ◽  
Frédéric Selle ◽  
Béatrice Weber ◽  
Isabelle-Laure Ray-Coquard ◽  
Ignace Vergote ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Disease Control ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Progression Free Survival ◽  
Platinum Resistant ◽  
Grade 3

Purpose Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinase. This phase II trial evaluated volasertib or single-agent chemotherapy in patients with platinum-resistant or -refractory ovarian cancer who experienced failure after treatment with two or three therapy lines. Patients and Methods Patients were randomly assigned to receive either volasertib 300 mg by intravenous infusion every 3 weeks or an investigator’s choice of single-agent, nonplatinum, cytotoxic chemotherapy. The primary end point was 24-week disease control rate. Secondary end points included best overall response, progression-free survival (PFS), safety, quality of life, and exploratory biomarker analyses. Results Of the 109 patients receiving treatment, 54 received volasertib and 55 received chemotherapy; demographics were well balanced. The 24-week disease control rates for volasertib and chemotherapy were 30.6% (95% CI, 18.0% to 43.2%) and 43.1% (95% CI, 29.6% to 56.7%), respectively, with partial responses in seven (13.0%) and eight (14.5%) patients, respectively. Median PFS was 13.1 weeks and 20.6 weeks for volasertib and chemotherapy (hazard ratio, 1.01; 95% CI, 0.66 to 1.53). Six patients (11%) receiving volasertib achieved PFS fore more than 1 year, whereas no patient receiving chemotherapy achieved PFS greater than 1 year. No relationship between the expression of the biomarkers tested and their response was determined. Patients treated with volasertib experienced more grade 3 and 4 drug-related hematologic adverse events (AEs) and fewer nonhematologic AEs than did patients receiving chemotherapy. Discontinuation resulting from AEs occurred in seven (13.0%) and 15 (27.3%) patients in the volasertib and chemotherapy arms, respectively. Both arms showed similar effects on quality of life. Conclusion Single-agent volasertib showed antitumor activity in patients with ovarian cancer. AEs in patients receiving volasertib were mainly hematologic and manageable.

Topotecan for the treatment of advanced epithelial ovarian cancer: an open-label phase II study in patients treated after prior chemotherapy that contained cisplatin or carboplatin and paclitaxel.

1998 ◽  
Vol 16 (10) ◽  
pp. 3345-3352 ◽  
Author(s):  
M A Bookman ◽  
H Malmström ◽  
G Bolis ◽  
A Gordon ◽  
A Lissoni ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Phase Ii ◽  
Group Performance ◽  
Phase Ii Study ◽  
Single Agent ◽  
Epithelial Ovarian Carcinoma ◽  
Response Analysis ◽  
Primary Therapy ◽  
Platinum Resistant

PURPOSE Topotecan, a topoisomerase I inhibitor, was evaluated in a multicenter, phase II study of women with epithelial ovarian carcinoma who relapsed after one or two prior regimens that included platinum and paclitaxel. PATIENTS AND METHODS Topotecan 1.5 mg/m2 daily was administered as a 30-minute infusion for 5 consecutive days on a 21-day cycle. Eligibility criteria included bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of 2 or less, and adequate bone marrow, liver, and renal function. Efficacy was assessed by independent radiologic review. RESULTS One hundred thirty-nine patients were treated; 81% were platinum resistant. Sixty-two patients had received one prior regimen and 77 patients had received two prior regimens. Nine patients were not assessable for response; however, all patients were included in the response analysis. The overall response rate was 13.7%; 12.4% in platinum-resistant and 19.2% in platinum-sensitive patients. Stable disease lasted at least 8 weeks in 27.3% of the patients. The median duration of response and time to progression were 18.1 and 12.1 weeks, respectively. The median survival was 47.0 weeks. Grade 4 neutropenia occurred in 82% of the patients (34% of the courses) and thrombocytopenia in 30% of the patients (9% of the courses). Infectious complications occurred in 6% of the courses. Nonhematologic toxicities were mild. There were no drug-related toxic deaths. CONCLUSION As a single agent, topotecan has modest activity in women with advanced epithelial ovarian carcinoma who have progressed or not responded after one or two prior regimens with platinum and paclitaxel. Further investigation of combination regimens is indicated in the primary therapy for ovarian cancer based on the mechanism of action and tolerability.

Phase II Study of Oxaliplatin in Platinum-Resistant and Refractory Ovarian Cancer: A Gynecologic Group Study

2003 ◽  
Vol 21 (15) ◽  
pp. 2856-2859 ◽  
Author(s):  
Paula M. Fracasso ◽  
John A. Blessing ◽  
Mark A. Morgan ◽  
Anil K. Sood ◽  
James S. Hoffman
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Response Duration ◽  
Complete Response ◽  
Epithelial Ovarian Carcinoma ◽  
Platinum Sensitive ◽  
Platinum Resistant

Purpose: A phase II study was conducted to determine the efficacy of oxaliplatin therapy in patients with platinum-resistant or refractory epithelial ovarian carcinoma. Materials and Methods: Eligible patients were to receive oxaliplatin 130 mg/m2 intravenously over 2 hours, every 21 days, until progression of disease or adverse effects prohibited further therapy. Results: Of 25 patients entered onto the study, 23 were eligible and assessable. There were no patients with complete response. One patient (4.3%) achieved a partial response, with a response duration of 6.4 months. Nine patients (39.1%) experienced stable disease, with a median duration of 5.6+ months (range, 1.8 to 13.1months). The most frequently reported drug-related toxicities were hematologic, gastrointestinal, and neurologic. Conclusion: Oxaliplatin as a single agent has minimal activity in patients with platinum-resistant or refractory ovarian cancer at the dosage and schedule tested. However, future studies of oxaliplatin combined with other active agents in women with platinum-naïve or platinum-sensitive epithelial ovarian carcinoma may be indicated.

A multicenter phase II study of the cryptophycin analog LY355703 in patients with platinum-resistant ovarian cancer

2006 ◽  
Vol 16 (1) ◽  
pp. 71-76 ◽  
Author(s):  
G D'AGOSTINO ◽  
J DEL CAMPO ◽  
B MELLADO ◽  
M.A. IZQUIERDO ◽  
T MINARIK ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Multicenter Phase ◽  
Platinum Resistant
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