Oral Etoposide Combined With Anlotinib in Advanced Triple Negative Breast Cancer

The hypothesis of this study is to discover if the oral Etoposide plus Anlotinib can shrink or slow the growth of pretreated advanced TNBC.

It is a single-arm, multicenter phase II clinical study of oral etoposide combined with antinib in the treatment of recurrent or metastatic triple-negative breast cancer

Study Overview

• Status: Recruiting
• Conditions: Triple Negative Breast Cancer
• Intervention / Treatment: Drug: oral etoposide + anlotinib

Detailed Description

It is a single-arm, multicenter phase II clinical study of oral etoposide combined with antinib in the treatment of recurrent or metastatic triple-negative breast cancer.

The hypothesis of this study is to discover if the oral Etoposide plus Anlotinib can shrink or slow the growth of pretreated advanced TNBC.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peng Yuan; Phone Number: 01087787245; Email: yuanpeng01@hotmail.com

Study Locations

• China
  • Beijing, China, 100021
    • Recruiting
    • Cancer Institute & Hospital. Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age between 18 and 75 year-old women; TNBC
• ECOG score: 0-1, expected survival time ≥ 3months;
• Pathologically or cytologically confirmed breast cancer;
• Anthracycline- / taxane- pretreated (adjuvant, neoadjuvant) breast cancer patients who have failed from 1-3 standard chemotherapies after recurrence and metastasis;
• According to RECIST 1.1, exist at least ≥1 measurable lesion(CT >1cm，other examination >2cm);

• The patients have enough organ function. The laboratory test indexes must comply with the following requirements:

  • Blood routine: neutrophil≥1.5G/L, platelet count ≥80G/L, hemoglobin ≥90g/L
  • Liver function: serum bilirubin ≤ 1.5 times the upper limit of normal value; ALT and AST≤2.5 times the upper limit of normal value; ALT and AST≤5 times the upper limit of normal value when liver metastasis
  • Renal function: serum creatinine ≤ 1.0times the upper limit of normal value, creatinine clearance >50ml/min（Cockcroft-Gault formula)
• Women of child-bearing age should be carried out pregnancy test (serum or urine) within 7 days before recruit, the results should be negative; and are willing to adopt the appropriate methods of contraception during the trial and 8 weeks after last administration；
• Can swallow oral drugs;
• The patients have good compliance to the therapy and follow-up to be scheduled and are able to understand the study protocol and sign the Informed Consent Form.

Exclusion Criteria:

• The patients in pregnancy or lactation growth period and did not take effective contraception;
• The patients who received ≥4 chemotherapies after recurrence and metastasis; involved in other clinical trials four weeks prior to the start of the study;
• The patients with a variety of factors that affect the oral administration and absorption of drugs;
• Prior treatment with etoposide or antiangiogenic TKI (subjects with prior use of antiangiogenic macromolecules such as bevacizumab are allowed to be enrolled);
• The patients have uncontrollable mental illness；
• Serous cavity effusion (such as pleural effusion and ascites) with clinical symptoms requiring clinical intervention or stable time less than 4 weeks;
• The patients who had serious adverse effect to oral etoposide or were allergic to etoposide.
• The patients who have only bone metastasis without other measurable lesion;
• The patients experience severe cardiovascular diseases;
• The patients experience severe upper gastrointestinal ulcer or malabsorption syndrome.
• Abnormal bone marrow functions(neutrophil<1.5G/L, platelet count <75G/L, hemoglobin <90g/L);
• Abnormal renal function(serum creatinine > 1.5 times the upper limit of normal value);
• Abnormal liver function(serum bilirubin ≤ 1.5 times the upper limit of normal value);
• The patients have uncontrollable brain metastasis;
• Active or uncontrolled infection requiring systematic treatment (except simple urinary tract infection or upper respiratory tract infection) during the 2 weeks or 2 weeks prior to enrollment;
• Previous or concurrent history of other malignant tumors.Except for the cured skin basal cell carcinoma and cervical carcinoma in situ;
• The patients do have good compliance to the therapy.

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: oral Etoposide+Anlotinib; anlotinib 12mg qd, d1-14，21days/cycle oral etoposide 75mg qd，d1-10，21days/cycle	Drug: oral etoposide + anlotinib; anlotinib 12mg qd, d1-14，21days/cycle oral etoposide 75mg qd，d1-10，21days/cycle; Other Names: there is no other intervention name

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate（ORR）	The ORR will be defined as the proportion of patients in the Efficacy Evaluable patient Set who achieve complete response (CR) and partial response (PR)	up to 1 year after the last patient enrolled

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival（PFS）	PFS will be defined as the time from first dose of study drug until documentation of disease progression or death from any cause	up to 1 year after the last patient enrolled
Incidence and Severity of adverse events	hematologic，hepatotoxicity，Incidence of hypertension，Incidence of proteinuria	approximately 1.5 years

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2020
• Primary Completion (Anticipated): July 11, 2022
• Study Completion (Anticipated): July 11, 2023

Study Registration Dates

• First Submitted: June 11, 2020
• First Submitted That Met QC Criteria: June 29, 2020
• First Posted (Actual): June 30, 2020

Study Record Updates

• Last Update Posted (Actual): July 21, 2021
• Last Update Submitted That Met QC Criteria: July 15, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etoposide
• Other Study ID Numbers: NCC2225

Drug and device information, study documents

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