8 Continuous vs 8 Intermittent Cycles in First and Second Line in HER2/Neu Neg Metastatic Breast Cancer

NCT ID: NCT01935492

Last Updated: 2020-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 420 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2019-04-01

Brief Summary

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.

Detailed 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.

Conditions

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

Study Design

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

Study Groups

8 cycles of Paclitaxel & bevacizumab

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

Group Type: ACTIVE_COMPARATOR

Paclitaxel, Bevacizumab, liposomal doxorubicin, Capecitabine

Intervention Type: DRUG

1. st line:

• Paclitaxel and bevacizumab: 8 cycles, unless PD or unacceptable toxicity occurs earlier.
• Bevacizumab until PD or unacceptable toxicity
• At PD patients will go to the 2nd treatment line.

2. nd line:

• Non-pegylated liposomal doxorubicin (Myocet®) (or capecitabine): 8 cycles, unless PD or unacceptable toxicity occurs earlier.
• At PD patients will go to the 3rd treatment line. If possible, it is advised to cross-over from 2nd line non-pegylated liposomal doxorubicin to 3rd line capecitabine.

2 x 4 cycles of Paclitaxel & bevacizumab

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

Group Type: ACTIVE_COMPARATOR

Paclitaxel, Bevacizumab, liposomal doxorubicin, Capecitabine

Intervention Type: DRUG

Arm B

1. st line

• Paclitaxel and bevacizumab: 4 cycles, unless PD or unacceptable toxicity
• Bevacizumab until PD or unacceptable toxicity
• At PD < 3 months after last paclitaxel start 2nd treatment line.
• At PD ≥ 3 months after last paclitaxel, start another 4 cycles
• Bevacizumab until the next PD or unacceptable toxicity
• At the next PD start the 2nd treatment line.

2. nd line:

• Myocet® or capecitabine: 4 cycles, unless PD or unacceptable toxicity
• At PD < 3 months start the 3rd treatment line. If possible, advised to cross-over from 2nd line Myocet® to 3rd line capecitabine.
• At PD ≥ 3 months after last administration of Myocet® or capecitabine, start another 4 cycles of Myocet® or capecitabine
• At the next PD start 3rd treatment line.

Interventions

Paclitaxel, Bevacizumab, liposomal doxorubicin, Capecitabine

1. st line:

• Paclitaxel and bevacizumab: 8 cycles, unless PD or unacceptable toxicity occurs earlier.
• Bevacizumab until PD or unacceptable toxicity
• At PD patients will go to the 2nd treatment line.

2. nd line:

• Non-pegylated liposomal doxorubicin (Myocet®) (or capecitabine): 8 cycles, unless PD or unacceptable toxicity occurs earlier.
• At PD patients will go to the 3rd treatment line. If possible, it is advised to cross-over from 2nd line non-pegylated liposomal doxorubicin to 3rd line capecitabine.

Intervention Type: DRUG

Paclitaxel, Bevacizumab, liposomal doxorubicin, Capecitabine

Arm B

1. st line

• Paclitaxel and bevacizumab: 4 cycles, unless PD or unacceptable toxicity
• Bevacizumab until PD or unacceptable toxicity
• At PD < 3 months after last paclitaxel start 2nd treatment line.
• At PD ≥ 3 months after last paclitaxel, start another 4 cycles
• Bevacizumab until the next PD or unacceptable toxicity
• At the next PD start the 2nd treatment line.

2. nd line:

• Myocet® or capecitabine: 4 cycles, unless PD or unacceptable toxicity
• At PD < 3 months start the 3rd treatment line. If possible, advised to cross-over from 2nd line Myocet® to 3rd line capecitabine.
• At PD ≥ 3 months after last administration of Myocet® or capecitabine, start another 4 cycles of Myocet® or capecitabine
• At the next PD start 3rd treatment line.

Intervention Type: DRUG

Other Intervention Names

Non-pegylated liposomal doxorubicin (Myocet®); Non-pegylated liposomal doxorubicin (Myocet®):

Eligibility Criteria

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

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

Sponsors

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Teva Pharma

INDUSTRY

Sponsor Role: collaborator

Borstkanker Onderzoek Groep

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

F.L.G. Erdkamp, PhD

Role: PRINCIPAL_INVESTIGATOR

Orbis Medical Centre

M.M.E.M. Bos, PhD

Role: PRINCIPAL_INVESTIGATOR

RdGG

Locations

BOOG Study Center

Amsterdam, , Netherlands

Countries

Netherlands

Related Links

http://www.boogstudycenter.nl

www.boogstudycenter.nl

Other Identifiers

NTR2589

Identifier Type: REGISTRY

Identifier Source: secondary_id

BOOG 2010-02 Stop&Go study

Identifier Type: -

Identifier Source: org_study_id