Clinical trial NCT01989780: Bevacizumab Plus Paclitaxel Optimization Study With Interventional Aintenance Endocrine Therapy in Breast Cancer
Official title: 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-
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Lead sponsor: Japan Breast Cancer Research Group
Sponsor class: OTHER
Collaborators: name: Chugai Pharmaceutical
First posted: 2013-11-21
Enrollment: 160
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Time to failure of strategy (TFS)
timeFrame: 2.5 years
Secondary outcomes:
measure: 2y Overall Survival rate
timeFrame: 3.5 years
measure: Overall Survival
timeFrame: 3.5years
measure: Progression Free Survival(PFS)
timeFrame: 2.5years
measure: QOL
timeFrame: 2.5years
measure: Biomarker(IMPACT assay Chips, whole blood, tumor tissue, Serum)
timeFrame: 2.5years
measure: Safety(Collection of adverse events)
timeFrame: 2.5years
Other outcomes:
Locations:
city: Chuo-ku, Nihonbashi, Koami-cho
country: Japan
facility: Japan Breast Cancer Research Group
state: Tokyo
Study officials:
affiliation: Kyoto University, Graduate School of Medicine
name: Masakazu Toi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fukushima Medical University
name: Shigehira Saji, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.