8 Continuous vs 8 Intermittent Cycles in First and Second Line in HER2/Neu Neg Metastatic Breast Cancer (Stop&Go)

Borstkanker Onderzoek Groep

Status and phase: Completed; Phase 3

Conditions: Metastatic Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast

Treatments: Drug: Paclitaxel, Bevacizumab, liposomal doxorubicin, Capecitabine

Study type: Interventional

Funder types: NETWORK; Industry

Identifiers

NCT01935492

NTR2589 (Registry Identifier)

BOOG 2010-02 Stop&Go study

Details and patient eligibility

About

An open randomized phase III study to compare 8 continuous cycles of chemotherapy with 8 cycles of intermittent (2 times 4 cycles) chemotherapy in first line treatment, in combination with bevacizumab, and second line treatment of patients with HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer.

Full description

The primary goal of this non-inferiority trial is to determine if the results obtained with a intermittent chemotherapy regimen (2 x 4 cycles of paclitaxel) are not inferior to the results of a continuous chemotherapy regimen (8 cycles of paclitaxel), both combined with bevacizumab in first line treatment of patients with HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer.

Enrollment: 420 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Female patients ≥ 18 years old.
• Patients with HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer, who are candidates for chemotherapy.
• Patients with measurable or evaluable-only (RECIST 1.1)
• Documented Estrogen Receptor (ER) / Progesteron Receptor (PR) status.
• HER2/neu-negative disease
• Patients with an ECOG Performance Status ≤ 2.
• Life expectancy of > 12 weeks.
• Signature of Informed Consent Form

Exclusion criteria

• Previous chemotherapy for HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer.
• Prior hormonal therapy for HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer that has not been discontinued 1 week before start of study treatment.
• Prior adjuvant/neo-adjuvant chemotherapy within 6 months prior to first study treatment. However, if the prior adjuvant/neo-adjuvant chemotherapy was taxane based, patients are excluded if they received their last chemotherapy within12 months prior to first study treatment.
• Prior radiotherapy covering more than 30% of marrow-bearing bone.
• Patients that have received recent radiation therapy that are not recovered from any significant (Grade ≥ 3) acute toxicity prior to study treatment.
• Prior therapy with bevacizumab, sorafenib, sunitinib, or other VEGF pathway-targeted therapy.
• Chronic daily treatment with aspirin
• Chronic daily treatment with corticosteroids, with the exception of inhaled steroids.
• Current or recent treatment with another investigational drug or participation in another investigational study.
• Inadequate bone marrow, liver, renal function
• INR > 1.5 or an aPTT > 1.5 x ULN within 7 days prior to first study treatment.
• Known CNS disease, except for treated brain metastases.
• Patients with concurrent active malignancy
• Pregnant or lactating
• Women of childbearing potential not using effective, non-hormonal means of contraception
• Major surgical procedure (including open biopsy) within 28 days prior to the first study treatment
• Core biopsy or other minor surgical procedure, within 7 days prior to day 1.
• Significant vascular disease within 6 months prior to day 1.
• Any previous venous thrombo-embolism > CTC Grade 3.
• History of haemoptysis
• History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
• Uncontrolled hypertension
• Clinically significant (i.e. active) cardiovasculair disease
• LVEF by MUGA or ECHO < 50%.
• History of abdominal fistula, Grade 4 bowel obstruction or GI perforation, intra-abdominal abscess within 6 months of randomization.
• Serious non-healing wound, peptic ulcer or bone fracture.
• Known hypersensitivity to any of the study drugs or excipients.
• Hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.
• Psychiatric illness, physical examination or laboratory findings that may interfer with protocol

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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420 participants in 2 patient groups

8 cycles of Paclitaxel & bevacizumab

Active Comparator group

Description:

8 cycles of Paclitaxel: 90 mg/m2 IV on days 1, 8 and 15 every 28 days \& Bevacizumab: 10 mg/kg IV on days 1 and 15 every 28 days

Treatment:

Drug: Paclitaxel, Bevacizumab, liposomal doxorubicin, Capecitabine

Drug: Paclitaxel, Bevacizumab, liposomal doxorubicin, Capecitabine

2 x 4 cycles of Paclitaxel & bevacizumab

Active Comparator group

Description:

intermittent 2x4 cycles of Paclitaxel: 90 mg/m2 IV on days 1, 8 and 15 every 28 days \& Bevacizumab: 10 mg/kg IV on days 1 and 15 every 28 days

Treatment:

Drug: Paclitaxel, Bevacizumab, liposomal doxorubicin, Capecitabine

Drug: Paclitaxel, Bevacizumab, liposomal doxorubicin, Capecitabine