Low -Dose-bevacizumab and Pemetrexed Versus TPC in Metastatic HER2-negative Breast Cancer Patients

NCT ID: NCT02829008

Last Updated: 2016-07-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2020-04-30

Brief Summary

This is a single-center, open, randomized, controlled phase 2 clinical trial designed to compare low-dose-bevacizumab and pemetrexed with TPC in metastatic HER2-negative breast cancer patients after failure of taxanes and anthracycline-containing regimens.

Detailed Description

There is no standard therapy for advanced human epidermal growth factor receptor 2 (HER2) -negative breast cancer patients after failure of taxanes and anthracycline-containing regimens at present. Pemetrexed is a multitargeted antimetabolite. Its efficacy in metastatic breast cancer has been confirmed in several small sample size studies and meta-analyses. Its response rate (RR) is about 30%, and will be higher in HER2-negative breast cancer. However, there is no study focused on this subtype of breast cancer. Bevacizumab is also an effective alternative for metastatic breast cancer. Several studies indicate that the combination of bevacizumab and chemotherapy could improve both RR and overall survival, but its use is confined by its severe side effect and far from adequate treatment. Recent years, a lot of studies have assessed the efficacy of metronomic chemotherapy. Metronomic therapy refers to the chronic administration of low doses of cytotoxic drugs at close, regular intervals. It could promote the apoptosis of tumor endothelial cell , continuously inhibit tumor angiogenesis, and exhibit a significant superiority of low toxicity, reduced cost and prolonged combination therapy period. According to reports in literature, the expression of anti-angiogenic biomarkers, such as,vascular endothelial growth factor(VEGF)-A, VEGF-C, soluble vascular endothelial growth factor receptor (sVEGFR)-1, sVEGFR-2,thrombospondin-1(TSP-1), platelet factor 4 (PF-4) might be concerned with the efficacy of metronomic therapy. Since there are no reported clinical trials according to metronomic bevacizumab in HER2-negative breast cancer, the investigators come up with this study. In this study, the investigators try to make a comparison of the efficacy and safety of low-dose-bevacizumab and pemetrexed with treatment of physician's choice (TPC) in metastatic breast cancer after failure of taxanes and anthracycline-containing regimens, to validate the correlative biomarkers and to find an optimal choice for previously treated metastatic breast cancer patients.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

low-dose-bevacizumab/Pemetrexed

Low-dose-bevacizumab is given at a dose of 2 mg/kg once weekly by intravenous transfusion, which is on day 1, 8 and 15, and every three weeks are a treatment cycle .Pemetrexed is given at a dose of 500mg/m2 once on the first day by intravenous transfusion, and repeated every three weeks, too. The pretreatment of pemetrexed should be conducted within the study.

Group Type: EXPERIMENTAL

low-dose-bevacizumab/pemetrexed

Intervention Type: DRUG

Bevacizumab is administrated at a dose of 2 mg/kg once weekly by intravenous transfusion, which is on day 1, 8 and 15, and pemetrexed is given at a dose of 500mg/m2 once on the first day by intravenous transfusion, and repeated every three weeks, too.

Treatment of physician' choice

Treatment of physician's choice can be any drug or regimen that has been approved in metastatic cancer at present, including monotherapy, combination therapy, target therapy and palliative therapy. It can be drugs like taxanes,capecitabine, gemcitabine, cisplatin, everolimus or even nutrient solution,et al.

Group Type: ACTIVE_COMPARATOR

Treatment of physician's choice

Intervention Type: DRUG

The clinicians can select any drug or regimen that has been approved in metastatic cancer at present, including monotherapy, combination therapy, target therapy and palliative therapy. Specific agents include taxanes, capecitabine, gemcitabine, vinorelbine, cisplatin,carboplatin, nutrient solutions, and so on. These agents can be administered as monotherapy or in combination.

Interventions

low-dose-bevacizumab/pemetrexed

Bevacizumab is administrated at a dose of 2 mg/kg once weekly by intravenous transfusion, which is on day 1, 8 and 15, and pemetrexed is given at a dose of 500mg/m2 once on the first day by intravenous transfusion, and repeated every three weeks, too.

Intervention Type: DRUG

Treatment of physician's choice

The clinicians can select any drug or regimen that has been approved in metastatic cancer at present, including monotherapy, combination therapy, target therapy and palliative therapy. Specific agents include taxanes, capecitabine, gemcitabine, vinorelbine, cisplatin,carboplatin, nutrient solutions, and so on. These agents can be administered as monotherapy or in combination.

Intervention Type: DRUG

Other Intervention Names

Avastin/ALIMTA; any drug or regimen approved in metastatic cancer

Eligibility Criteria

Inclusion Criteria

1. Metastatic breast cancer females confirmed by pathological and/or cytological examination;

2. Breast cancer patients who received taxanes and anthracycline-containing regimens previously;

3. HER2-negative breast cancer patients confirmed by immunohistochemical test or fluorescent in situ hybridization(FISH);

4. Patients aged from 18-70 years old, and patients with Eastern Cooperative Oncology Group（ECOG） performance status scored 0-2;

5. One or more measurable lesions in imaging examination,with a diameter no less than 20mm in ordinary computed tomography (CT) or magnetic resonance imaging (MRI), or a scanning diameter no less than 10mm in spiral CT;

6. Any other kind of concomitant chemotherapy is not allowed during the research. If the patients had accepted other chemotherapy before recruitment, he can enter into the study until the drug is eliminated 30 days later;

7. Patients without any kind of major organ dysfunction: normal blood test results, normal function of heart, liver, kidney, marrow and so on.

Exclusion Criteria

1. Patients who had received any chemotherapy, radiotherapy, biotherapy, or drugs and physical treatment in other clinical trials four weeks within the enrollment;

2. Patients who has no measurable or assessable lesions ;

3. Patients with moderate or severe liver dysfunction

4. Pregnant or lactational patients;

5. Patients with severe complications, including severe heart disease, cerebrovascular disease, uncontrolled diabet and hypertension, severe infection , active peptic ulcer and so on;

6. Patient who had previously received pemetrexed-containing regimens in metastatic setting.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Chinese Academy of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Li Qiao

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Binghe Xu, MD.

Role: PRINCIPAL_INVESTIGATOR

Chinese Academy of Medical Sciences

Locations

Cancer Hospital, ChineseAMS

Beijing, Beijing Municipality, China

Countries

China

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Other Identifiers

CAMS-LQOO2

Identifier Type: OTHER

Identifier Source: secondary_id

LQ002

Identifier Type: -

Identifier Source: org_study_id