Vinorelbine Plus Apatinib Versus Vinorelbine in Advanced Triple-Negative Breast Cancer

A Phase II, Single-center, Randomized Study of Vinorelbine Plus Apatinib Versus Vinorelbine as Second-Line or Third-Line Treatment in Patients With Advanced Triple-Negative Breast Cancer (NAN Trail)

Vinorelbine Plus Apatinib Versus Vinorelbine in Advanced Triple-Negative Breast Cancer

Study Overview

• Status: Completed
• Conditions: Advanced Triple-Negative Breast Cancer
• Intervention / Treatment: Drug: Vinorelbine; Drug: Apatinib

Detailed Description

A Phase II, Single-center, Randomized Study of Vinorelbine Plus Apatinib Versus Vinorelbine as Second-Line or Third-Line Treatment in Patients With Advanced Triple-Negative Breast Cancer (NAN trail)

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200032
    • Fudan University Cancer Hospital

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:

1. Performance Status 0-1
2. Life expectancy longer than 3 months
3. Histological proven unresectable recurrent or advanced breast cancer
4. Triple-negative for estrogen receptor (ER), progestogen receptor (PR), and human epithelial receptor-2 (HER2) by immunohistochemistry (ER <1%, PR <1% and Her2 negative). A negative Her2 gene amplification should be verified by FISH test for those patients with Her2 (2+)
5. Patients must have progressed after 1 or 2 prior chemotherapy regimens for metastatic disease, and consistent with the following treatment failure definition: progress in the first-line or second-line regimen treatment, or follow-up disease progression less than 3 months after completion of their last dose
6. At least one extracranial measurable disease according to the response evaluation criteria in solid tumor (RECIST 1.1)
7. Radiation therapy within 4 weeks prior to enrollment
8. All patients enrolled are required to have adequate hematologic, hepatic, and renal function
9. Be able to understand the study procedures and sign informed consent

Exclusion Criteria:

1. Patients had prior treatment with vinorelbine
2. Pregnant or lactating women, women of child-bearing potential, unwilling to use adequate contraceptive protection during the process of the study
3. Patients with symptomatic central nervous system metastases are not permitted, except for those with stable and asymptomatic brain metastases who have completed cranial irradiation, and have at least one measurable lesion outside the brain. Radiotherapy should be completed within 4 weeks prior to the registration
4. Treatment with an investigational product within 4 weeks before the first treatment
5. Severe cardiopulmonary insufficiency, severe hepatic and renal dysfunction
6. Uncontrolled serious infection
7. Unhealed wound or bone fracture
8. Patients with hypertension and uncontrolled hypertension with hypotensive drugs therapy (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg). Patients with grade I or above myocardial ischemia or myocardial infarction or arrhythmia (including QT interval ≥ 440 ms) or cardiac insufficiency
9. Inability to swallow, gastrointestinal resection, chronic diarrhea and obstruction of the intestine, various factors which affect drug use and absorption
10. Coagulation disorders (PT > 16 s, APTT > 43 s, TT > 21 s, Fbg < 2g / L) Being treated with thrombolytic or anticoagulant therapy, with bleeding tendency or definite gastrointestinal bleeding concerns (eg: local active ulcer lesions, fecal occult blood + + or above)
11. Artery or venous thrombosis occurred within 6 months before the study begins, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, and pulmonary embolism, etc.
12. Patient who has a history of psychotropic substance abuse and is unable to stop or have a history of mental disorders
13. Have received prior treatment with a VEGFR TKI (Bevacizumab is permitted)
14. Another malignancy within 5 years, except for cured basal cell carcinoma of the skin and cervical carcinoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Vinorelbine Plus Apatinib; Vinorelbine: 20 mg/m2, D6, D13, D20 Apatinib: 250 mg/d, D1-5, D8-12, D15-19. The starting dose will be 250mg/d in the first cycle, if tolerable, 500 mg/d will be administered from the cycle 2.	Drug: Vinorelbine; Experimental: 20 mg/m2, D6, D13, D20 Active Comparator: 25 mg/m2, D1, D8, D15; Other Names: NVB; Drug: Apatinib; 250 mg/d, D1-5, D8-12, D15-19. The starting dose will be 250mg/d in the first cycle, if tolerable, 500 mg/d will be administered from the cycle 2.
ACTIVE_COMPARATOR: Vinorelbine; Vinorelbine: 25 mg/m2, D1, D8, D15	Drug: Vinorelbine; Experimental: 20 mg/m2, D6, D13, D20 Active Comparator: 25 mg/m2, D1, D8, D15; Other Names: NVB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression Free Survival	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall Survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
ORR	Objective Response Rate	6 weeks
Safety: Number of Participants with Adverse Events	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	6 weeks

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 16, 2017
• Primary Completion (ACTUAL): August 1, 2021
• Study Completion (ACTUAL): August 1, 2021

Study Registration Dates

• First Submitted: August 17, 2017
• First Submitted That Met QC Criteria: August 17, 2017
• First Posted (ACTUAL): August 18, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 20, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

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; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Vinorelbine; Apatinib
• Other Study ID Numbers: Fudan BR2017-23

Drug and device information, study documents

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