Study of Fludarabine With Pegylated Liposomal Doxorubicin Versus Pegylated Liposomal Doxorubicin Alone In Patients With Platinum Resistant/Refractory Ovarian Cancer

An Open-label, Randomised Phase II Study of Fludarabine With Pegylated Liposomal Doxorubicin Versus Pegylated Liposomal Doxorubicin Alone In Patients With Platinum Resistant/Refractory Ovarian Cancer

The purpose of the study is to evaluate the efficacy and toxicity of fludarabine with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in patients with platinum resistant or refractory ovarian cancer.

Study Overview

• Status: Unknown
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Fludarabine and Pegylated liposomal doxorubicin; Drug: Pegylated liposomal doxorubicin

Detailed Description

Ovarian cancer is the leading cause of death for patients with gynecologic malignancies. Approximately 75% of patients are diagnosed at an advanced stage will eventually experience disease recurrence. The overall response rates of second-line chemotherapy for recurrent ovarian cancer are only 20-27%. The 5-year overall survival rates are less than 20%. Therefore, it is important to seek alternative agent that can improve the outcome. Fludarabine is a purine nucleoside analog prodrug that upon phosphorylation is toxic to dividing and quiescent lymphocytes and monocytes, exerting its effects through DNA synthesis interference and apoptosis. The preclinical studies suggest fludarabine may be effective in other cancers such as ovarian cancer. Therefore, the purpose of this study is to test the efficacy and safety of the study drug fludarabine combined with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in patients with platinum resistant or refractory ovarian cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer
      • Contact: Yin Wang; Phone Number: +86-20-87343104; Email: wangyin@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically or pathologically confirmed diagnosis of epithelial carcinoma of the ovary.
• Platinum resistant or refractory ovarian cancer
• At least treated with one line of platinum-based chemotherapy
• Female, age ≥18 years and ≤70 years, signed informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 version
• Patients must have a life expectancy of at least 3 months.

• Patients must have adequate organ function as defined by the following criteria:

  • White blood cell count ≥ 3 x 10^9/L, Absolute neutrophil count (ANC) (≥ 1.0 x 10^9/L), Hemoglobin of ≥ 80 g/L, Platelets ≥ 80 x 10^9/L
  • Total bilirubin ≤ 1 x upper limit of normal (ULN), AST and ALT ≤ 2.5 x ULN
  • Serum creatinine ≤ 1 x ULN
• Symptomatic central nervous system (CNS) metastasis

Exclusion Critera:

• Has known allergies to any of the excipients.
• Prior treatment with adriamycin or other anthracycline at cumulative doses greater than 550 mg/m2 after 6 cycles of pegylated liposomal doxorubicin
• LVEF (left ventricular ejection fraction) <50%
• Had disease recurrence/progression within 6 months after the administration of doxorubicin chemotherapy
• History of myocardial infarction, or unstable angina, or New York Heart Association (NYHA) Grade III-IV within 6 months prior to Day 1.
• Known significant chronic liver disease, such as cirrhosis or active hepatitis
• Uncontrollable active infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Fludarabine and Pegylated liposomal doxorubicin	Drug: Fludarabine and Pegylated liposomal doxorubicin; Fludarabine 25mg/m2 iv on days d1-d3 of each 4-week cycle Pegylated liposomal doxorubicin 30mg/m2 iv every 4 weeks
Active Comparator: Arm 2: Pegylated liposomal doxorubicin	Drug: Pegylated liposomal doxorubicin; Pegylated liposomal doxorubicin 50mg/m2 iv every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival estimated using Kaplan-Meier methods is defined as the time from registration to the earlier of death or disease progression. Patients alive without disease progression are censored at the date of last disease evaluation. Progressive disease (PD) based on RECIST 1.0 is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Equivocal progression of non-target lesions also qualifies as PD	Up to four years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	Objective response rate defined as confirmed complete response or partial response under RECIST 1.0 criteria. CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met.	Up to four years

Other Outcome Measures

Outcome Measure	Time Frame
Frequency and severity of adverse effects as defined by CTCAE version 4.0	30 days after last dose

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: November 1, 2017
• First Submitted That Met QC Criteria: November 2, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Actual): November 13, 2017
• Last Update Submitted That Met QC Criteria: November 8, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Chemotherapy; Ovarian Cancer; Fludarabine; Pegylated Liposomal Doxorubicin
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin; Fludarabine
• Other Study ID Numbers: 308-2016-03-01

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No