Real-World Effectiveness of PLD in Platinum- Sensitive Recurrent Ovarian Cancer

NCT ID: NCT03562533

Last Updated: 2019-02-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

432 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-05-17

Study Completion Date

2018-12-17

Brief Summary

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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

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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.

Conditions

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Ovarian Carcinoma

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

RETROSPECTIVE

Study Groups

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pegylated liposomal doxorubicin + carboplatin

carboplatin area under the curve \[AUC\] 5 plus pegylated liposomal doxorubicin (PLD) 30 mg/m2 every 4 weeks

pegylated liposomal doxorubicin (PLD) + carboplatin (CD)

Intervention Type DRUG

carboplatin AUC 5 plus paclitaxel 175 mg/m2 every 3 weeks for at least 6 cycles

paclitaxel + carboplatin

carboplatin AUC 5 plus paclitaxel 175 mg/m2 every 3 weeks

carboplatin + paclitaxel (CP)

Intervention Type DRUG

carboplatin AUC 5 plus paclitaxel 175 mg/m2 every 3 weeks for at least 6 cycles

Interventions

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pegylated liposomal doxorubicin (PLD) + carboplatin (CD)

carboplatin AUC 5 plus paclitaxel 175 mg/m2 every 3 weeks for at least 6 cycles

Intervention Type DRUG

carboplatin + paclitaxel (CP)

carboplatin AUC 5 plus paclitaxel 175 mg/m2 every 3 weeks for at least 6 cycles

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Previous taxane therapy was required.
* Recurred \>6 months after surgery and first-line platinum-based chemotherapy regimen
* Patients with measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) or CA-125 assessable disease according to Gynecologic Cancer InterGroup (GCIG) criteria or histologic proven diagnosis
* Eastern Cooperative Oncology Group performance status of ≤ 2

Exclusion Criteria

* Had ovarian tumors of low malignant potential (borderline tumors); nonepithelial or mixed epithelial/nonepithelial tumors (eg, mixed Mullerian tumors)
* Had received prior radiotherapy; or, had a previous diagnosis of malignancy within the past 5 years.
* Had bowel obstruction or presence of symptomatic brain metastases
* Patients with severe active infection
* Had history of severe hypersensitivity reactions to compounds chemically related to study products.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Seoul National University Hospital

OTHER

Sponsor Role collaborator

National Cancer Center, Korea

OTHER_GOV

Sponsor Role collaborator

Asan Medical Center

OTHER

Sponsor Role collaborator

The Catholic University of Korea

OTHER

Sponsor Role collaborator

Samsung Medical Center

OTHER

Sponsor Role collaborator

Chung-Ang University Hosptial, Chung-Ang University College of Medicine

OTHER

Sponsor Role collaborator

Ajou University

OTHER

Sponsor Role collaborator

Severance Hospital

OTHER

Sponsor Role collaborator

Konkuk University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Seung Hyuk Shim, MD

Role: PRINCIPAL_INVESTIGATOR

Konkuk University Hospital

Locations

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Konkuk University School of Medicine

Seoul, , South Korea

Site Status

Countries

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South Korea

References

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Park SJ, Kim J, Kim HS, Lee JW, Chang HK, Lee KH, Kim DY, Kim S, Chang SJ, Han SS, Park SY, Shim SH. Real world effectiveness and safety of pegylated liposomal doxorubicin in platinum-sensitive recurrent ovarian, fallopian, or primary peritoneal cancer: a Korean multicenter retrospective cohort study. J Gynecol Oncol. 2020 Mar;31(2):e15. doi: 10.3802/jgo.2020.31.e15. Epub 2019 Sep 10.

Reference Type DERIVED
PMID: 31912673 (View on PubMed)

Other Identifiers

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KUH1040075

Identifier Type: -

Identifier Source: org_study_id