A Study to Evaluate the Safety and Efficacy of Caelyx in Combination With Carboplatin in Patients With Ovarian Cancer Recurrent Within Six to Twelve Months After Initial Carboplatin and Paclitaxel Chemotherapy (P03625)

Phase II, Open-Label, Study of CAELYX and Carboplatin Intermediate Platinum-Sensitive (6-12 Months Treatment-free Interval) Relapsed Epithelial Ovarian Cancer.

Doxorubicin has been used to treat ovarian cancer as part of different combination therapies, but high cumulative doses should be avoided because of the risk of cardiotoxicity. Pegylated Liposomal Doxorubicin (Caelyx) has been developed to reduce the risk of cardiotoxicity. The purpose of this study is to evaluate the safety and efficacy of Caelyx in combination with carboplatin in women with recurrent ovarian cancer.

Study Overview

• Status: Completed
• Conditions: Ovarian Neoplasms
• Intervention / Treatment: Drug: Pegylated Liposomal Doxorubicin; Drug: Carboplatin

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age >=18 years old
• Subject must have histological diagnosis of epithelial ovarian cancer
• Subject must have received a taxane and platinum regimen and have maintained a treatment-free status for at least six months and not more than twelve months following completion of first line therapy.
• Subject must have measurable ovarian cancer by appropriate radiological imaging.
• ECOG performance Score of 0 or 1.
• Subject's life expectancy must be > 6 months.

• Subject must have normal organ function, except if abnormal due to tumor involvement:

  • Adequate bone marrow function (platelets >=100 X 10^9/L, hemoglobin >=100 g/L, neutrophils >=1.5 X 10^9/L)
  • Adequate renal function (serum creatinine<=1.5 X the upper limit of normal (ULN)
  • Adequate liver function (bilirubin and AST or ALT<=2 times ULN, unless related to primary disease.
• MUGA scan must indicate left ventricular ejection fraction above 90%.
• Women of childbearing potential must be using adequate contraception (prescribed under medical supervision) and have a negative pregnancy test at the time of enrollment.
• Subject must be able to sign written informed consent.

Exclusion Criteria:

• Subject who is pregnant or is breast feeding.
• Subject who has history of cardiac disease, with New York Heart Association Class II or greater.
• Subject with a history of severe hypersensitivity reactions to products containing Cremophor® EL.
• Subject with clinically significant hepatic disease.
• Subject who has uncontrolled bacterial, viral, or fungal infection.
• Subject who exhibits confusion or disorientation.
• Subject with any condition that would prevent adequate follow-up.
• Subject with a history of prior malignancy treated with systemic chemotherapy or radiotherapy.
• Subject who has received two or more prior chemotherapy regimens for ovarian cancer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single Arm; Caelyx 30 mg/m2 in combination with carboplatin dosed to target AUC of 5 mg/mL.min.

Drug: Pegylated Liposomal Doxorubicin; Subjects will receive Caleyx 30 mg/m2 intravenously on Day 1 of each 4-week cycle, during 6 cycles. Patients still achieving clinical benefit after a total of 6 cycles may continue therapy.; Other Names: SCH 200746; Drug: Carboplatin; Subjects will receive carboplatin dosed to target AUC of 5 mg/mL.min, intravenously, on Day 1 of each 4-week cycle, after the Caelyx infusion, during 6 cycles. Patients still achieving clinical benefit after a total of 6 cycles may continue therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete response rate, according to RECIST criteria; Partial response rate, according to RECIST criteria	Complete or partial response: re-evaluation 4 weeks later to confirm response; Upon completion of chemotherapy: follow-up every 2 months until documentation of progressive disease; All patients will be followed for a minimum of one year for survival

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability; Duration of response; CA-125 response; Time to progression; Overall survival	All patients will be followed for a minimum of one year for survival

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Princess Margaret Hospital, Canada

Publications and helpful links

General Publications

• Li KJ, Garoff H. Packaging of intron-containing genes into retrovirus vectors by alphavirus vectors. Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3650-4. doi: 10.1073/pnas.95.7.3650.
• Power P, Stuart G, Oza A, Provencher D, Bentley JR, Miller WH Jr, Pouliot JF. Efficacy of pegylated liposomal doxorubicin (PLD) plus carboplatin in ovarian cancer patients who recur within six to twelve months: a phase II study. Gynecol Oncol. 2009 Sep;114(3):410-4. doi: 10.1016/j.ygyno.2009.04.037. Epub 2009 Jun 10.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2003
• Primary Completion (Actual): September 6, 2007
• Study Completion (Actual): September 6, 2007

Study Registration Dates

• First Submitted: October 23, 2008
• First Submitted That Met QC Criteria: October 23, 2008
• First Posted (Estimate): October 24, 2008

Study Record Updates

• Last Update Posted (Actual): May 15, 2017
• Last Update Submitted That Met QC Criteria: May 12, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Carboplatin; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: P03625

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No