Clinical trial NCT02867956: Apatinib and Etoposide in Patients With Platinum Resistant or Refractory Ovarian Cancer
Official title: A Phase II Study of Apatinib In Combination With Etoposide in Patients With Platinum Resistant or Refractory Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Ovarian cancer
Apatinib
Etoposide
Chemotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2016-08-16
Enrollment: 35
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the efficacy and toxicity of apatinib in patients with platinum resistant or refractory ovarian cancer when combined with etoposide.

Detailed description: Ovarian cancer is the leading cause of death for patients with gynecologic malignancies. In most cases, the disease is diagnosed at an advanced stage and approximately 75% of patients will eventually experience disease recurrence. However, the overall response rates of second-line chemotherapy for recurrent ovarian cancer are only 20-27%. Therefore, it is important to seek alternative agent that can improve the outcome. Apatinib is a novel vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor and it has been approved for the treatment of advanced gastric cancer. The preclinical studies suggest apatinib 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 apatinib when combined with a standard treatment, etoposide, for 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 ovarian cancer (defined as relapsing within 6 months after the last administration of platinum-based chemotherapy) OR platinum refractory ovarian cancer (defined as progressing while on a platinum-based chemotherapy)
* 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) (≥ 1.5 x 10\^9/L), Hemoglobin of ≥ 80 g/L, Platelets ≥ 70 x 10\^9/L
  * Total bilirubin ≤ 1 x upper limit of normal (ULN), AST and ALT ≤ 2 x ULN
  * Serum creatinine ≤ 1 x ULN

Exclusion Criteria:

* Had prior exposure to apatinib or has known allegies to any of the excipients.
* History of myocardial infarction, or unstable angina, or New York Heart Association (NYHA) Grade III-IV within 6 months prior to Day 1.
* Patients with QT interval prolongation
* Serious, non-healing wound, active ulcer, bowel obstruction.
* History of abdominal fistula or gastrointestinal perforation within 28 days prior to Day 1
* Evidence of bleeding diathesis or coagulopathy
* Inadequately controlled hypertension
* Major surgical procedure within 28 days prior to Day 1
* Symptomatic central nervous system (CNS) metastasis

Primary outcomes:
measure: Objective response rate
timeFrame: Up to three years
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to three years
measure: Duration of Response
timeFrame: Up to three years
measure: Frequency and severity of adverse effects as defined by CTCAE version 4.03
timeFrame: 30 days after last dose
measure: Overall survival (OS)
timeFrame: Up to three years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Xin Huang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huang X, Xie C, Tang J, He W, Yang F, Tian W, Li J, Yang Q, Shen J, Xia L, Lan C. Adipose tissue area as a predictor for the efficacy of apatinib in platinum-resistant ovarian cancer: an exploratory imaging biomarker analysis of the AEROC trial. BMC Med. 2020 Oct 5;18(1):267. doi: 10.1186/s12916-020-01733-4.
citation: Lan CY, Wang Y, Xiong Y, Li JD, Shen JX, Li YF, Zheng M, Zhang YN, Feng YL, Liu Q, Huang HQ, Huang X. Apatinib combined with oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer (AEROC): a phase 2, single-arm, prospective study. Lancet Oncol. 2018 Sep;19(9):1239-1246. doi: 10.1016/S1470-2045(18)30349-8. Epub 2018 Aug 3.