Clinical trial NCT03335241: Study of Fludarabine With Pegylated Liposomal Doxorubicin Versus Pegylated Liposomal Doxorubicin Alone In Patients With Platinum Resistant/Refractory Ovarian Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Ovarian Cancer
Fludarabine
Pegylated Liposomal Doxorubicin
Chemotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2017-11-07
Enrollment: 140
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to four years
Secondary outcomes:
measure: Objective response rate
timeFrame: Up to four years
Other outcomes:
measure: Frequency and severity of adverse effects as defined by CTCAE version 4.0
timeFrame: 30 days after last dose
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer
state: Guangdong
Study officials:
References: