Trial | NCT01935492  Report issue

Title

8 Continuous vs 8 Intermittent Cycles in First and Second Line in HER2/Neu Neg Metastatic Breast Cancer
8 Continuous vs 8 Intermittent Cycles in First and Second Line Treatment of Patients With HER2/Neu Negative, Incurable, Metastatic or Unresectable Locally Advanced Breast Cancer.

  • Phase

    Phase 3

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    420
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.
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.
Study Started
Nov 30
2010
Primary Completion
Apr 01
2019
Study Completion
Apr 01
2019
Last Update
Jan 18
2020

Drug Paclitaxel, Bevacizumab, liposomal doxorubicin, Capecitabine

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. 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.

  • Other names: Non-pegylated liposomal doxorubicin (Myocet®)

Drug Paclitaxel, Bevacizumab, liposomal doxorubicin, Capecitabine

Arm B 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. 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.

  • Other names: Non-pegylated liposomal doxorubicin (Myocet®):

8 cycles of Paclitaxel & bevacizumab Active Comparator

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

2 x 4 cycles of Paclitaxel & bevacizumab Active Comparator

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

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
No Results Posted