BOOSTER: Bevacizumab Plus Paclitaxel Optimization Study With Interventional Aintenance Endocrine Therapy in Breast Cancer
Study Details
Study Description
Brief Summary
To compare continuing bevacizumab + paclitaxel or switching to bevacizumab + endocrine maintenance therapy followed by bevacizumab + paclitaxel, after 1st line induction therapy with bevacizumab + paclitaxel in ER+HER2- advanced or metastatic breast cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This multicenter, randomized Phase II study of patients with advanced or metastatic estrogen receptor-positive human epidermal receptor type 2-negative breast cancer aims to compare two treatment strategies following induction therapy with 4-6 cycles of the combined use of weekly paclitaxel (wPTX) and bevacizumab (BV). In arm A, wPTX+BV is continued, while in arm B, wPTX is switched to maintenance endocrine therapy (hormone+BV) until disease progression, followed by wPTX+BV re-induction. The primary endpoint is time to failure of strategy, which is the time from randomization to a qualifying event (addition of a new agent not in the primary regimen, progressive disease during or after planned therapy, or death).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Arm A weekly paclitaxel + bevacizumab |
Drug: Paclitaxel
Other Names:
Drug: Bevacizumab
Other Names:
|
| Experimental: Arm B endocrine therapy* + bevacizumab then back to weekly paclitaxel + bevacizumab therapy (*Letrozole, Anastrozole, Exemestane, Fulvestrant, LHRH Analogs + Aromatase inhibitors.) |
Drug: Paclitaxel
Other Names:
Drug: Bevacizumab
Other Names:
Drug: Letrozole
Other Names:
Drug: Anastrozole
Other Names:
Drug: Exemestane
Other Names:
Drug: Fulvestrant
Other Names:
Drug: Goserelin
Other Names:
Drug: leuprorelin
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Time to failure of strategy (TFS) [2.5 years]
Secondary Outcome Measures
- 2y Overall Survival rate [3.5 years]
- Overall Survival [3.5years]
- Progression Free Survival(PFS) [2.5years]
- QOL [2.5years]
- Biomarker(IMPACT assay Chips, whole blood, tumor tissue, Serum) [2.5years]
vascular endothelial growth factor(VEGF)-A, VEGFR-2, VEGF-C, platelet derived growth factor(PDGF)-C, Soluble fms-like tyrosine kinase-1, VEGFR-3, Interleukin(IL)-8, Basic Fibroblast Growth Factor(FGFb), placental growth factor(PLGF), E-Selectin, intercellular adhesion molecule(ICAM)-1, neuropilin of Tumor tissue, single nucleotide polymorphism(SNP):VEGFR-1 and VEGF of whole blood DNA, angiotensin(ANG) and Apelin of serum.
- Safety(Collection of adverse events) [2.5years]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed adenocarcinoma of the breast
-
Female aged 20-75 years old at getting informed consent
-
HER2 negative disease (IHC 0/1+ or 2+ with FISH negative)
-
Documented estrogen receptor (ER) positive (>=1% by IHC)
-
Inoperative locally advanced or metastatic breast cancer at enrolment
-
Performance status (ECOG): 0-1 at enrolment
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Life expectancy of at least 3 months from enrolment
-
No prior systemic therapy for recurrent breast cancer (excluding hormone therapy)
-
No prior neo and/or adjuvant chemotherapy with taxane or adjuvant setting with a disease-free interval from completion of the taxane treatment to metastatic diagnosis of >= 12 months
-
Patients with measurable lesion regarding with Response Evaluation Criteria in Solid Tumors(RECIST) criteria or who have evaluable lesion
-
Patients with only bone lesion will be acceptable if the osteolytic lesion has a measurable soft tissue component by MRI or CT
-
No influence on protocol treatment is considered in case prior therapy or examination.
-
Adequate following organ function within 2 weeks before starting treatment. The latest examination results should be adopted and blood transfusion or treatment of hematopoietic factor drugs is not allowed 2 weeks before examination.
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Absolute neutrophil count >= 1500 /mm3 or white blood cell(WBC) count >= 3000 /mm3
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Platelets >=10 x 10000 /mm3
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Hb >= 9 g/dL
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Total bilirubin <= 1.5 mg/dL
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aspartate aminotransferase(AST) and alanine aminotransferase(ALT) <= 100 international unit(IU)/L
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Serum creatinine <= 1.5 mg/dL
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Urine dipstick for proteinuria <= 1+
- Written informed consent signed by patients before completing any treatment related procedure
Exclusion Criteria:
-
Prior therapy with bevacizumab
-
Active infection requiring intrvenous antibiotics at enrollment or infection with active HBV and/or HCV.
-
Pregnancy, lactetion or in case of potentialy pregnancy women Not mind contraception in trial period.
-
Known hypersensitivity to bevacizumab or paclitaxel
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History of hemoptysis (>= 2.5mL of bright red blood per episord).
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Use of disulfiram,cyanamide, carmofur or procarbazine Hydrochloride
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Patients with CNS metastases (except for not symptomatic)
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Persistent Grade >= 2 sensory neuropathy at enrollment
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Grade 3 >= hypertension (>= 2 use of antihypertensive drug)
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Evidence with arterial thromboembolism (Cerebral infarction, Myocardial infarction) or history within 1 year prior to enrollment.
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Evidence withvenous thromboembolism (deep vein thrombosis, pulmonary embolism) or history within 1 year prior to enrollment.
-
History of GI perforation and/or serious abdominal fistula within 1 year prior to enrollment
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Cases that the investigator judged as inappropriate as the subject of this clinical study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Japan Breast Cancer Research Group | Chuo-ku, Nihonbashi, Koami-cho | Tokyo | Japan | 1030016 |
Sponsors and Collaborators
- Japan Breast Cancer Research Group
- Chugai Pharmaceutical
Investigators
- Principal Investigator: Masakazu Toi, MD, PhD, Kyoto University, Graduate School of Medicine
- Principal Investigator: Shigehira Saji, MD, PhD, Fukushima Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- JBCRG-M04
- UMIN000012179