Apatinib Combined With PLD vs PLD for Platinum-resistant Recurrent Ovarian Cancer

NCT04348032 | Unknown Phase 2

• 1 other identifier: 2016YFC1303704
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 16

Brief Summary

Epithelial ovarian cancer is the most fatal gynecological malignancy. Despite initial therapeutic response, the majority of advanced-stage patients relapse and eventually succumb to chemoresistant disease. The prognosis of patients with platinum-resistant or refractory ovarian cancer was very poor, with the response rate of 20%\~25% after chemotherapy. The purpose of treatment for recurrent ovarian cancer is mainly to improve the quality of life of patients and prolong survival. Angiogenesis is essential for tumor growth and metastasis.And VEGF/VEGF receptor(VEGFR) signaling pathway is the most promising angiogenic target due to its key roles in angiogenesis and tumor growth.This study sought to assess the efficacy and safety of the combination therapy of apatinib and PLD, clarifying whether combination therapy could improve the outcomes of patients with platinum-resistant recurrent ovarian cancer.

Conditions

Platinum-resistant Recurrent Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival(PFS)

  From date of randomization until the date of first documented progression or died

  up to 2 years

Secondary Outcomes (4)

• Overall survival(OS)

  up to 2 years

• Objective response rate(ORR)

  up to 2 years

• disease control rate(DCR)

  up to 2 years

• hematological toxicity and non-hematological toxicity

  up to 2 years

Study Arms (2)

PLD

ACTIVE COMPARATOR

PLD 40 mg/m2 D1 ivgtt q4w

Drug: PLD 40mg/m2 ivgtt q4w

PLD + Apatinib

EXPERIMENTAL

PLD 40 mg/m2 D1 ivgtt q4w + Apatinib 250mg po qd

Drug: PLD 40mg/m2 ivgtt q4w +Apatinib 250mg po qd

Interventions

PLD 40mg/m2 ivgtt q4w +Apatinib 250mg po qd DRUG

Patients receive PLD and apatinib at the same time. The dose of intravenous chemotherapy drug is calculated according to the body surface area, and the dose of oral drug apatinib is 250mg qd. Dose suspension and dose reduction are allowed only when patients have serious adverse reactions. The intravenous chemotherapy drug PLD dose is only allowed to be down-regulated twice (one time is to reduce the standard dose by 25%), and the oral drug apatinib dose is only allowed to be reduced once (250mg gravity QD changed to 250mg gravity Qod). Otherwise the patients will drop out of the study.

PLD + Apatinib

PLD 40mg/m2 ivgtt q4w DRUG

The dose of intravenous chemotherapy drug is calculated according to the body surface area. When patients have serious adverse reactions, dose suspension and dose reduction are allowed. The PLD dose is only allowed to be down-regulated twice (one time is to reduce the standard dose by 25%).

PLD

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients were diagnosed with ovarian cancer, fallopian tube cancer or primary peritoneal cancer confirmed by previous pathology, and the pathological type was non-mucinous adenocarcinoma.There were previous surgical wax preservation.
• Initial platinum-resistant relapse, the recurrence time was less than 6 months after the last chemotherapy.
• Complicated with malignant pleural effusion or ascites, or with recurrent lesions that can be evaluated clinically.
• ECOG physical status score 0 or 1.
• The expected survival time is ≥ 4 months.
• In the previous treatment, there was no antivascular targeted therapy;
• Patients without pleural effusion or ascites should be confirmed by CT or MRI according to the standard of RECIST1.1 version, requiring the patient to have at least one measurable focus as the target focus. If the target focus is a lymph node with a short diameter of more than 1.5 cm, and the target focus is not suitable for surgical treatment, the target focus has not received radiotherapy or relapsed in the radiotherapy field.
• The baseline blood routine conforms to the following criteria:
• neutrophil count ≥ 1.5x109 /L;
• platelet count ≥ 100x109 PG L;
• hemoglobin ≥ 9g/dL (blood transfusion is allowed to achieve or maintain this target) .
• Liver function meets the following criteria:
• total bilirubin\<1.5 normal limit (ULN);
• glutamic oxaloacetic transaminase (AST), glutamic pyruvic transaminase (ALT)\<2.5xULN, which is allowed\<5xULN in patients with liver metastasis.
• Serum creatinine ≤ 1.25xULN or calculated creatinine clearance ≥ 50mL/min.

You may not qualify if:

• Have received more than two chemotherapy regimens in the past.
• Currently or recently (within 30 days before enrollment) using another research drug or participating in another clinical study.
• other malignant tumors have occurred within 5 years (except adequately treated cervical carcinoma in situ or skin squamous cell carcinoma, or controlled basal cell carcinoma of the skin).
• Patients with hypertension that cannot be reduced to normal range after antihypertensive treatment (systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg).
• Suffer from myocardial ischemia or myocardial infarction above II grade and poorly controlled arrhythmias (including QTc interval ≥ 470ms in females).
• According to the NYHA standard, there were previous or present cardiac insufficiency of grade II or above, or color Doppler echocardiography showed that the left ventricular ejection fraction ((LVEF)) was less than 50% or the lower limit of the normal value.
• Abnormal coagulation function (INR\>1.5 or prothrombin time (PT) \> ULN+4 seconds or APTT\>1.5xULN), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy.
• There were significant clinical bleeding symptoms or definite bleeding tendency in the first 3 months, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood or above, or suffering from vasculitis.
• Major surgical operations or severe traumatic injuries, fractures or ulcers occurred within the first 4 weeks of randomization.
• There are significant factors affecting oral drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction.
• Urine routine indicates urinary protein ≥++, or confirms 24-hour urinary protein ≥ 1.0g.
• The researchers judged other conditions that may affect the conduct of clinical studies and the determination of research results.
• Allergic or heterogeneous reactions to doxorubicin and / or related substances.
• The cumulative dose of doxorubicin (including previous anthracycline, if any) is expected to reach or exceed 550 mg after 4 courses of doxorubicin liposome injection treatment.
• Uncontrollable arrhythmias or electrocardiograms abnormalities determined by the lead researcher to be at risk.

Sponsors & Collaborators

• Chinese Academy of Medical Sciences: lead
• Jiangsu HengRui Medicine Co., Ltd.: collaborator

Study Sites (16)

National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, Beijing Municipality, 100021, China

Location

Beijing Obstetrics and Gynecology Hospital affiliated to Capital Medical University

Beijing, Beijing Municipality, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Location

Peking University Cancer Hospital

Beijing, Beijing Municipality, China

Location

Chongqing Cancer Hospital

Chongqing, Chongqing Municipality, 400030, China

Location

Guangxi Cancer Hospital

Guangxi, Guangxi, China

Location

Hubei Cancer Hospital

Hubei, Hubei, China

Location

Hunan Cancer Hospital

Hunan, Hunan, China

Location

Xiangya Hospital of Central South University

Hunan, Hunan, China

Location

The first Hospital of Jilin University

Jilin, Jilin, China

Location

Liaoning Cancer Hospital

Liaoyang, Liaoning, China

Location

Shandong Cancer Hospital

Shangdong, Shangdong, China

Location

Tumor Hospital affiliated to Fudan University

Shanghai, Shanghai Municipality, China

Location

West China Second University Hospital, Sichuan University

Chengdu, Sichuan, 100021, China

Location

Tumor Hospital of Tianjin Medical University

Tianjin, Tianjin Municipality, China

Location

Yunnan Cancer Hospital

Yunnan, Yunnan, China

Location

Related Publications (3)

• Newhouse R, Nelissen E, El-Shakankery KH, Rogozinska E, Bain E, Veiga S, Morrison J. Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Jul 5;7(7):CD006910. doi: 10.1002/14651858.CD006910.pub3.

  PMID: 37407274 DERIVED

• Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

  PMID: 37185961 DERIVED

• Wang T, Tang J, Yang H, Yin R, Zhang J, Zhou Q, Liu Z, Cao L, Li L, Huang Y, Jiang K, Wang W, She F, Guan N, Hou Z, Li N, Wu L. Effect of Apatinib Plus Pegylated Liposomal Doxorubicin vs Pegylated Liposomal Doxorubicin Alone on Platinum-Resistant Recurrent Ovarian Cancer: The APPROVE Randomized Clinical Trial. JAMA Oncol. 2022 Aug 1;8(8):1169-1176. doi: 10.1001/jamaoncol.2022.2253.

  PMID: 35771546 DERIVED

MeSH Terms

Interventions

1-dodecylpyridoxal

Study Officials

• Lingying Wu, MD

  Chinese Academy of Medical Sciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: April 14, 2020
• First Posted: April 15, 2020
• Study Start: March 22, 2018
• Primary Completion: January 28, 2021
• Study Completion: June 30, 2022
• Last Updated: March 31, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (16)