Bevacizumab Plus Paclitaxel Optimization Study With Interventional Aintenance Endocrine Therapy in Breast Cancer (BOOSTER)

Bevacizumab Plus Paclitaxel Optimization Study With Interventional Maintenance Endocrine Therapy in Advanced or Metastatic ER-positive HER2-negative Breast Cancer -BOOSTER Trial, a Multicenter Randomized Phase II Study-

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Fulvestrant; Drug: Letrozole; Drug: Paclitaxel; Drug: Anastrozole; Drug: Bevacizumab; Drug: Exemestane; Drug: Goserelin; Drug: leuprorelin

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 Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Chuo-ku, Nihonbashi, Koami-cho, Tokyo, Japan, 1030016
      • Japan Breast Cancer Research Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of the breast
2. Female aged 20-75 years old at getting informed consent
3. HER2 negative disease (IHC 0/1+ or 2+ with FISH negative)
4. Documented estrogen receptor (ER) positive (>=1% by IHC)
5. Inoperative locally advanced or metastatic breast cancer at enrolment
6. Performance status (ECOG): 0-1 at enrolment
7. Life expectancy of at least 3 months from enrolment
8. No prior systemic therapy for recurrent breast cancer (excluding hormone therapy)
9. 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
10. Patients with measurable lesion regarding with Response Evaluation Criteria in Solid Tumors(RECIST) criteria or who have evaluable lesion
11. Patients with only bone lesion will be acceptable if the osteolytic lesion has a measurable soft tissue component by MRI or CT
12. No influence on protocol treatment is considered in case prior therapy or examination.

13. 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.

    • Absolute neutrophil count >= 1500 /mm3 or white blood cell(WBC) count >= 3000 /mm3
    • Platelets >=10 x 10000 /mm3
    • Hb >= 9 g/dL
    • Total bilirubin <= 1.5 mg/dL
    • aspartate aminotransferase(AST) and alanine aminotransferase(ALT) <= 100 international unit(IU)/L
    • Serum creatinine <= 1.5 mg/dL
    • Urine dipstick for proteinuria <= 1+
14. Written informed consent signed by patients before completing any treatment related procedure

Exclusion Criteria:

1. Prior therapy with bevacizumab
2. Active infection requiring intrvenous antibiotics at enrollment or infection with active HBV and/or HCV.
3. Pregnancy, lactetion or in case of potentialy pregnancy women Not mind contraception in trial period.
4. Known hypersensitivity to bevacizumab or paclitaxel
5. History of hemoptysis (>= 2.5mL of bright red blood per episord).
6. Use of disulfiram,cyanamide, carmofur or procarbazine Hydrochloride
7. Patients with CNS metastases (except for not symptomatic)
8. Persistent Grade >= 2 sensory neuropathy at enrollment
9. Grade 3 >= hypertension (>= 2 use of antihypertensive drug)
10. Evidence with arterial thromboembolism (Cerebral infarction, Myocardial infarction) or history within 1 year prior to enrollment.
11. Evidence withvenous thromboembolism (deep vein thrombosis, pulmonary embolism) or history within 1 year prior to enrollment.
12. History of GI perforation and/or serious abdominal fistula within 1 year prior to enrollment
13. Cases that the investigator judged as inappropriate as the subject of this clinical study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; weekly paclitaxel + bevacizumab	Drug: Paclitaxel; Other Names: Taxol; Drug: Bevacizumab; Other Names: Avastin
Experimental: Arm B; endocrine therapy* + bevacizumab then back to weekly paclitaxel + bevacizumab therapy (*Letrozole, Anastrozole, Exemestane, Fulvestrant, LHRH Analogs + Aromatase inhibitors.)	Drug: Fulvestrant; Other Names: Faslodex; Drug: Letrozole; Other Names: Femara; Drug: Paclitaxel; Other Names: Taxol; Drug: Anastrozole; Other Names: Arimidex; Drug: Bevacizumab; Other Names: Avastin; Drug: Exemestane; Other Names: Aromasin; Drug: Goserelin; Other Names: Zoladex; Drug: leuprorelin; Other Names: Leuplin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to failure of strategy (TFS)	2.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	2.5years
Safety(Collection of adverse events)		2.5years

Collaborators and Investigators

• Sponsor: Japan Breast Cancer Research Group
• Collaborators: Chugai Pharmaceutical
• Investigators: Principal Investigator: Masakazu Toi, MD, PhD, Kyoto University, Graduate School of Medicine

Publications and helpful links

General Publications

• Saji S, Taira N, Kitada M, Takano T, Takada M, Ohtake T, Toyama T, Kikawa Y, Hasegawa Y, Fujisawa T, Kashiwaba M, Ishida T, Nakamura R, Yamamoto Y, Toh U, Iwata H, Masuda N, Morita S, Ohno S, Toi M. Switch maintenance endocrine therapy plus bevacizumab after bevacizumab plus paclitaxel in advanced or metastatic oestrogen receptor-positive, HER2-negative breast cancer (BOOSTER): a randomised, open-label, phase 2 trial. Lancet Oncol. 2022 May;23(5):636-649. doi: 10.1016/S1470-2045(22)00196-6. Epub 2022 Apr 8.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: November 4, 2013
• First Submitted That Met QC Criteria: November 15, 2013
• First Posted (Estimate): November 21, 2013

Study Record Updates

• Last Update Posted (Actual): August 4, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Estrogen Receptor Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Paclitaxel; Letrozole; Fulvestrant; Leuprolide; Goserelin; Bevacizumab; Anastrozole; Exemestane
• Other Study ID Numbers: JBCRG-M04; UMIN000012179 (Registry Identifier: UMIN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Deidetified patient data will be made available upon reasonable request.