Clinical trial NCT01935492: 8 Continuous vs 8 Intermittent Cycles in First and Second Line in HER2/Neu Neg Metastatic Breast Cancer
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
Metastatic Breast Cancer
Keywords: metastatic breast cancer
HER2/neu negative
paclitaxel
bevacizumab
liposomal doxorubicine
capecitabine
Lead sponsor: Borstkanker Onderzoek Groep
Sponsor class: NETWORK
Collaborators: name: Roche Pharma AG
name: Teva Pharma
First posted: 2013-09-05
Enrollment: 420
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression free survival
timeFrame: 1 year
Secondary outcomes:
measure: Progression free survival second line treatment
timeFrame: 1 year
measure: Objective overall response rate
timeFrame: 1 year
measure: Duration of objective response
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
measure: Safety and tolerability. The total number of grade 3 and 4 adverse events will be analyzed.
timeFrame: 1 year
measure: Quality of life measures
timeFrame: 1 year
measure: Pharmacoeconomics
timeFrame: 1 year
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: BOOG Study Center
Study officials:
affiliation: Orbis Medical Centre
name: F.L.G. Erdkamp, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: RdGG
name: M.M.E.M. Bos, PhD
role: PRINCIPAL_INVESTIGATOR
References: