A randomized, open-label study comparing trabectedin and pegylated liposomal doxorubicin with pegylated liposomal doxorubicin alone for the treatment of advanced-relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer (ET743-OVC-3006)

Abstract BACKGROUND: Pegylated liposomal doxorubicin (CAELYX®) is a liposomal formulation of doxorubicin sterically stabilized by the grafting of segments of polyethylene glycol (PEG) onto the liposomal surface. Given the demonstrated efficacy of VAD (vincristine and doxorubicin and oral dexamethasone) in Multiple Myeloma (MM) patients and the potential for CAELYX® to extend the duration of bone marrow exposure to therapeutic levels of doxorubicin, a combination regimen of CAELYX®, vincristine, and reduced-dose dexamethasone (DVD) has been actively investigated in MM patients. Studies showed that substituting CAELYX® for doxorubicin in the VAD regimen and reducing the dose of dexamethasone in MM patients improves the safety profile and convenience of the treatment regimen without compromising efficacy. Due to potential differences in metabolism of these patients, safety and efficacy results may vary. Thus, we carried out this study in 82 newly diagnosed MM patients in China, in order to demonstrate the efficacy and safety profiles of DVD. METHODS: Patients (n=82) from 15 sites were recruited in this study. CAELYX® (40mg/m2) was infused intravenously over 60-minutes, administered every 28 days. Vincristine (2.0mg) was administered intravenously on Day 1 of each cycle. Dexamethasone (40 mg) was administered from Day 1- Day 4 of each cycle orally or intravenously. The treatment was repeated every 28 days for 4 cycles. RESULTS: Upon ITT analysis, the overall response rate was approximately 68% (56/82); 11% of the patients achieved complete remission (CR), 40% achieved partial response (PR), 17% achieved minimal response; 15% had stable disease (SD), and 12% o had progressive disease (PD) after the treatment. The cumulative 4-month progression-free survival (PFS) was 88%. The incidence of all the adverse events was 46%. The most common non-hematological toxicities were palmar-plantar erythrodysesthesia (13.4%) and stomatitis (6.1%), respectively. CONCLUSION: Pegylated liposomal doxorubicin, vincristine and reduced dose dexamethasone combination (DVD) regimen is an effective and safe regimen in newly diagnosed multiple myeloma patients in Chinese population.

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An open-label study to evaluate dose and cycle dependence of the pharmacokinetics (PK) of pegylated liposomal doxorubicin (PLD)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.2012 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 2012-2012 ◽

Cited By ~ 2

Author(s):

A. Gabizon ◽

R. Isacson ◽

O. Rosengarten ◽

D. Tzemach ◽

H. Shmeeda ◽

...

Keyword(s):

Dose Range ◽

Pegylated Liposomal Doxorubicin ◽

Skin Toxicity ◽

Significant Inhibition ◽

Open Label ◽

Cycle Number ◽

Open Label Study ◽

Label Study ◽

Mean Values ◽

Significant Difference

2012 Background: There are no definitive data in humans on the dose dependency and/or cycle dependency of the pharmacokinetics of PLD. The skin toxicity of PLD tends to worsen after several treatment cycles. Therefore, it is important to characterize the PK of PLD after 2 or more cycles. Methods: Fifteen patients with various solid tumors were randomized to two arms of treatment in an open-label study. Arm A received PLD at doses of 60, 30, and 45 mg/m2 in 3 successive cycles every 4 weeks (q4w). Arm B received PLD at doses of 30, 60, and 45 mg/m2 in 3 successive cycles q4w. Twelve patients, 6 on each arm, completed all three cycles and were fully evaluable. Plasma levels of doxorubicin were analyzed by HPLC and fluorimetry following a previously published method (J Chromatogr B, 779:259–69, 2002) with minor modifications. PK analysis was done by non-compartmental method. The following parameters were obtained: Cmax, AUC∞, terminal half-life (T1/2), and Clearance (CL). The paired t test was used for statistical analysis. Results: There was no significant difference in the parameters examined when the dose was increased from 30 to 60 mg/m2. However, when we analyzed the effect of cycle number on the PK, we found a gradual and significant inhibition of CL when patients advance from the 1st through the 3rd cycle of PLD (p=0.0003), with a mean increase of 44% in AUC/mg dose (p=0.0011). Cmax and T1/2 mean values increased by 17% and 18% respectively between the 1st and 3rd cycles, but only the increase in T1/2 was statistically significant (p=0.0127). Conclusion: While the PK of PLD is not dose-dependent within the dose range of 30 to 60mg/m2, there is evidence of a cycle-dependent effect that results in inhibition of CL when patients receive successive cycles of PLD. This effect may account for the delayed skin toxicity of PLD. These results suggest the need for dose adjustments of PLD to minimize the risk of toxicity, such as an initial high loading dose followed by reduced maintenance doses from the 2nd or 3rd cycle onwards. [Table: see text] [Table: see text]

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A phase 2, open-label study of niraparib in women with advanced, relapsed, high-grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer after ≥3 previous chemotherapy regimens.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.tps5609 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. TPS5609-TPS5609 ◽

Cited By ~ 1

Author(s):

Kathleen N. Moore ◽

Bj Rimel ◽

Shefali Agarwal ◽

John Balser ◽

Robert E. Martell ◽

...

Keyword(s):

Fallopian Tube ◽

High Grade ◽

Phase 2 ◽

Open Label ◽

Open Label Study ◽

Label Study ◽

Primary Peritoneal Cancer ◽

Peritoneal Cancer

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MIRASOL (GOG 3045/ENGOT OV-55): A randomized, open-label, phase III study of mirvetuximab soravtansine versus investigator’s choice of chemotherapy in advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate-alpha (FRα) expression.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.tps6103 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. TPS6103-TPS6103

Author(s):

Kathleen N. Moore ◽

Toon Van Gorp ◽

Jiuzhou Wang ◽

Brooke Esteves ◽

Patrick A Zweidler-McKay

Keyword(s):

Fallopian Tube ◽

Single Agent ◽

Objective Response ◽

Pegylated Liposomal Doxorubicin ◽

Phase Iii ◽

Clinical Activity ◽

Antibody Drug Conjugate ◽

Open Label ◽

Fallopian Tube Cancer ◽

Phase Iii Study

TPS6103 Background: Elevated FRα expression is a characteristic of several solid tumors, including epithelial ovarian cancer (EOC), thereby providing an attractive candidate for targeted therapeutic approaches. Mirvetuximab soravtansine is an antibody-drug conjugate (ADC) comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent that has shown consistent and meaningful single agent clinical activity, along with favorable tolerability, in patients with high FRα expressing tumors. Methods: MIRASOL is a randomized phase III study designed to evaluate the efficacy of mirvetuximab soravtansine compared with that of standard-of-care chemotherapy in adult patients with platinum-resistant EOC, primary peritoneal cancer, or fallopian tube cancer. Confirmation of high FRα positivity by immunohistochemistry (high expression; ≥ 75% of cells with PS2+ staining intensity) and ≤ 3 prior lines of therapy are required for inclusion. MIRASOL is designed to randomize 430 patients, 1:1 to Arm 1 (intravenous mirvetuximab soravtansine at a dose of 6 mg/kg, calculated using adjusted ideal body weight, on Day 1 of a 21-day cycle) or Arm 2 (investigators’ choice chemotherapy: paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary efficacy endpoint is progression-free survival (PFS; by investigator) and secondary endpoints include objective response rate, quality of life, overall survival, and safety and tolerability. MIRASOL opened for enrollment in December 2019. Clinical trial information: NCT04209855.

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Randomized, Open-Label, Phase III Study Comparing Patupilone (EPO906) With Pegylated Liposomal Doxorubicin in Platinum-Refractory or -Resistant Patients With Recurrent Epithelial Ovarian, Primary Fallopian Tube, or Primary Peritoneal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2011.38.8082 ◽

2012 ◽

Vol 30 (31) ◽

pp. 3841-3847 ◽

Cited By ~ 74

Author(s):

Nicoletta Colombo ◽

Elzbieta Kutarska ◽

Meletios Dimopoulos ◽

Duk-Soo Bae ◽

Izabella Rzepka-Gorska ◽

...

Keyword(s):

Fallopian Tube ◽

Liposomal Doxorubicin ◽

Pegylated Liposomal Doxorubicin ◽

Progression Free Survival ◽

Phase Iii ◽

Open Label ◽

Primary Peritoneal Cancer ◽

Peritoneal Cancer ◽

Significant Difference ◽

Platinum Refractory

Purpose This study compared the efficacy and safety of patupilone with those of pegylated liposomal doxorubicin (PLD) in patients with platinum-refractory or -resistant epithelial ovarian, primary fallopian tube, or primary peritoneal cancer. Patients and Methods Patients with three or fewer prior regimens were eligible if they had received first-line taxane/platinum-based combination chemotherapy and were platinum refractory or resistant. Patients were randomly assigned to receive patupilone (10 mg/m2 intravenously every 3 weeks) or PLD (50 mg/m2 intravenously every 4 weeks). Results A total of 829 patients were randomly assigned (patupilone, n = 412; PLD, n = 417). There was no statistically significant difference in overall survival (OS), the primary end point, between the patupilone and PLD arms (P = .195; hazard ratio, 0.93; 95% CI, 0.79 to 1.09), with median OS rates of 13.2 and 12.7 months, respectively. Median progression-free survival was 3.7 months for both arms. The overall response rate (all partial responses) was higher in the patupilone arm than in the PLD arm (15.5% v 7.9%; odds ratio, 2.11; 95% CI, 1.36 to 3.29), although disease control rates were similar (59.5% v 56.3%, respectively). Frequently observed adverse events (AEs) of any grade included diarrhea (85.3%) and peripheral neuropathy (39.3%) in the patupilone arm and mucositis/stomatitis (43%) and hand-foot syndrome (41.8%) in the PLD arm. Conclusion Patupilone did not demonstrate significant improvement in OS compared with the active control, PLD. No new or unexpected serious AEs were identified.

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