Ignite Creation Date:
2025-12-25 @ 2:49 AM
Ignite Modification Date:
2025-12-26 @ 1:31 AM
Study NCT ID:
NCT03562533
Status:
COMPLETED
Last Update Posted:
2019-02-28
First Post:
2018-05-23
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Real-World Effectiveness of PLD in Platinum- Sensitive Recurrent Ovarian Cancer
Sponsor:
Konkuk University Medical Center
Organization:
Study Overview
Official Title:
Comparison of Real-World Effectiveness of Pegylated Liposomal Doxorubicin Versus Paclitaxel in Platinum- Sensitive Recurrent Ovarian Cancer
Status:
COMPLETED
Status Verified Date:
2019-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This retrospective multicenter study aimed to evaluate the effectiveness of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with carboplatin and paclitaxel (CP) in patients who had disease progression longer than 6 months after first-line platinum+taxane chemotherapy for ovarian cancer in real world clinical practice.
Detailed Description:
Worldwide, ovarian cancer is the sixth most common cancer and the seventh most common cause of cancer deaths in women. At the time of presentation, approximately 70% of women have advanced disease. Despite standard treatment of initial debulking surgery followed by chemotherapy in advanced ovarian cancer, most patients relapse after achieving a complete clinical response. Disease that responds to first-line therapy but relapses after 6 months after completion of initial platinum-based therapy is considered platinum sensitive (PS). Chemotherapy re-treatment is an important aspect in the overall management of patients with PS relapsed or recurrent ovarian cancer (ROC). Platinum is a backbone of treatment, and carboplatin and paclitaxel (CP) have emerged as standard in the first-line setting and been rechallenged in patients with platinum-sensitive ROC. A pooled analysis of three phase III trials from the AGO-OVAR and International Collaborative Ovarian Neoplasm collaborators demonstrated significant improvements in progression-free survival (PFS; hazard ratio \[HR\], 0.76; 95% confidence interval \[CI\], 0.66 to 0.89; P = .0004) and overall survival (OS; HR, 0.82; 95% CI, 0.69 to 0.97; P = .02) in patients with PS ROC treated with platinum-paclitaxel versus conventional platinum based therapies, mainly carboplatin monotherapy.
However, rechallenge with CP has been limited by the risk of cumulative peripheral neuropathy. In addition, grade 2 alopecia (complete hair loss), another ill-tolerated adverse effect for patients facing the distress of relapse, occurs in more than 80% of patients. In order to improve the patient's tolerance on the treatment in this setting, other carboplatin-based combinations, such as gemcitabine and carboplatin, have been explored. This combination significantly improved PFS versus carboplatin alone in phase III trial (HR, 0.72; 95%CI, 0.58 to 0.90; P= .0031). however, OS was not significantly improved (HR, 0.96; 95% CI, 0.75 to 1.23; P = .735); the trial was not powered to detect a survival difference. Grade 3 to 4 hematologic toxicities were significantly more frequent in the combination arm. Thus, a need for other carboplatin combinations remains in PS ROC.
Pegylated liposomal doxorubicin (PLD) is an active drug in ROC as the efficacy has been demonstrated in CALYPSO trial.
CAYPSO is a large randomized phase III showing the noninferiority of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with CP in patients with PS ROC. In this trial, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Overall severe nonhematologic toxicity (36.8% v 28.4%; P = .01) leading to early discontinuation (15% v 6%; P = .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm.
Moreover, recent subgroup analysis of CALYPSO trial had reported that CD had a more favorable risk-benefit profile than CP in patients with partially platinum-sensitive ROC (patients with a treatment-free interval of \>6 and ≤12 months). The hazard ratio for PFS was 0.73 (95% CI: 0.58-0.90; P = 0.004 for superiority) in favor of CD.
On the basis of the results of CALYPSO trial, Korea Food \& Drug Administration (KFDA) has approved and reimbursed the use of PLD in patients with PS ROC since August 2014. From then, approximately 700 patients with PS ROC have been treated with PLD in Korea.
The majority of patients enrolled in CALYPSO have 1 prior treatment, however, CD has been used in diverse setting of ROC in Korea. Therefore, the effectiveness and safety of the PLD combination should be still evaluated in the real clinical practice in Korea. To fulfill the gap of knowledge between clinical trials and actual clinical practice, we perform a multicenter, retrospective, observational study of CD therapy in the second line setting of PS ROC.
However, rechallenge with CP has been limited by the risk of cumulative peripheral neuropathy. In addition, grade 2 alopecia (complete hair loss), another ill-tolerated adverse effect for patients facing the distress of relapse, occurs in more than 80% of patients. In order to improve the patient's tolerance on the treatment in this setting, other carboplatin-based combinations, such as gemcitabine and carboplatin, have been explored. This combination significantly improved PFS versus carboplatin alone in phase III trial (HR, 0.72; 95%CI, 0.58 to 0.90; P= .0031). however, OS was not significantly improved (HR, 0.96; 95% CI, 0.75 to 1.23; P = .735); the trial was not powered to detect a survival difference. Grade 3 to 4 hematologic toxicities were significantly more frequent in the combination arm. Thus, a need for other carboplatin combinations remains in PS ROC.
Pegylated liposomal doxorubicin (PLD) is an active drug in ROC as the efficacy has been demonstrated in CALYPSO trial.
CAYPSO is a large randomized phase III showing the noninferiority of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with CP in patients with PS ROC. In this trial, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Overall severe nonhematologic toxicity (36.8% v 28.4%; P = .01) leading to early discontinuation (15% v 6%; P = .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm.
Moreover, recent subgroup analysis of CALYPSO trial had reported that CD had a more favorable risk-benefit profile than CP in patients with partially platinum-sensitive ROC (patients with a treatment-free interval of \>6 and ≤12 months). The hazard ratio for PFS was 0.73 (95% CI: 0.58-0.90; P = 0.004 for superiority) in favor of CD.
On the basis of the results of CALYPSO trial, Korea Food \& Drug Administration (KFDA) has approved and reimbursed the use of PLD in patients with PS ROC since August 2014. From then, approximately 700 patients with PS ROC have been treated with PLD in Korea.
The majority of patients enrolled in CALYPSO have 1 prior treatment, however, CD has been used in diverse setting of ROC in Korea. Therefore, the effectiveness and safety of the PLD combination should be still evaluated in the real clinical practice in Korea. To fulfill the gap of knowledge between clinical trials and actual clinical practice, we perform a multicenter, retrospective, observational study of CD therapy in the second line setting of PS ROC.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: