Know Cancer

or
forgot password

Safety and Tolerability of Bevacizumab Plus Paclitaxel vs. Bevacizumab Plus Metronomic Cyclophosphamide and Capecitabine as First-Line Therapy in Patients With HER2-Negative Metastatic or Locally Recurrent Breast Cancer - A Multicenter, Randomized Phase III Trial


Phase 3
18 Years
N/A
Open (Enrolling)
Female
Breast Cancer

Thank you

Trial Information

Safety and Tolerability of Bevacizumab Plus Paclitaxel vs. Bevacizumab Plus Metronomic Cyclophosphamide and Capecitabine as First-Line Therapy in Patients With HER2-Negative Metastatic or Locally Recurrent Breast Cancer - A Multicenter, Randomized Phase III Trial


OBJECTIVES:

- To determine if bevacizumab and paclitaxel versus bevacizumab, metronomic
cyclophosphamide, and capecitabine as first-line therapy causes less medication-related
adverse events in women with HER2-negative metastatic, locally advanced, or recurrent
breast cancer.

- To compare quality of life (QOL) in patients treated with these regimens.

- To replicate previous findings of better QOL in patients with complete response or
partial response versus stable disease for 6 months or greater.

- To determine the predictive value of baseline QOL for the duration of a meaningful
change in QOL of patients treated with chemotherapy.

- To determine the associations between the QOL endpoints, selected health economics, and
clinical endpoints.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor response
(measurable vs evaluable disease), WHO performance status (0 or 1 vs 2), and center.
Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and
paclitaxel IV on days 1, 8, and 15. Treatment repeats every 4 weeks in the absence of
disease progression or unacceptable toxicity.

- Arm II: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral
cyclophosphamide once daily on days 1-28, and oral capecitabine 3 times a day on days
1-28. Treatment repeats every 4 weeks in the absence of disease progression or
unacceptable toxicity.

Patients complete quality-of-life questionnaire (BL-QA) and health economics questionnaires
(BL-HEA and EQ-5D) at baseline, during, and after completion of study therapy.

After completion of study treatment, patients are followed up at 1 month, every 3 months for
1 year, and then every 6 months for 1 year.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed adenocarcinoma of the breast

- Locally advanced, recurrent, or metastatic disease

- HER2-negative disease

- Measurable or evaluable disease

- Candidate for taxane-based chemotherapy

- No presence or history of CNS metastasis

- Clinical suspicion of CNS metastasis must be confirmed by CT or MRI scan

- Hormone receptor status not specified

PATIENT CHARACTERISTICS:

- Menopausal status not specified

- WHO performance status 0-2

- Neutrophil count ≥ 1.5 x 10^9/L

- Platelet count ≥ 100 x 10^9/L

- Hemoglobin ≥ 80 g/L

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST ≤ 5 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN in case of liver metastases or ≤
10 times ULN in case of bone metastases)

- Serum creatinine ≤ 1.5 times ULN

- Urine protein < 2+ by dipstick OR ≤ 1 g by 24-hour urine collection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 12 months after
completion of study therapy

- Patients with INR > 1.5 (or Quick ≤ 70%) OR aPTT > 1.5 times ULN within 7 days prior
to expected first trial treatment must be receiving anticoagulant medication

- Patients receiving full-dose oral or parental anticoagulants may be included in
the trial provided anticoagulant dosing has been stable for at least 2 weeks
prior to trial entry and the appropriate coagulation monitoring tests are within
local therapeutic limits

- Must be compliant and geographically proximal for staging and follow-up

- No previous malignancy within the past 5 years except for adequately treated
carcinoma in situ of the cervix or localized nonmelanoma skin cancer

- No known hypersensitivity to trial drugs or its active compound (e.g.,
fluoropyrimidine), any other components of the trial drugs, or drugs formulated with
cremophor EL including hypersensitivity to Chinese hamster ovary cell products or any
other humanized recombinant antibodies

- No preexisting peripheral motor or sensory neuropathy > NCI CTCAE grade 2 (i.e.,
moderate symptoms or limiting instrumental activities of daily living)

- No history or evidence of inherited bleeding diathesis, coagulopathy with the risk of
bleeding, serious nonhealing wound, active peptic ulcer, nonhealing bone fracture, or
bleeding metastases

- No history of abdominal fistula, grade 4 bowel obstruction, or gastrointestinal
perforation or intra-abdominal abscess within the past 6 months

- No evidence of other medical conditions that would impair the ability of the patient
to participate in the trial or might preclude therapy with trial drugs, including any
of the following:

- DPD deficiency

- Severe respiratory, cardiac, hepatic, or renal disease

- Active infection

- Uncontrolled diabetes mellitus

- Uncontrolled hypertension ≥ 140/100 mm Hg

- Myocardial infarction within the past 12 months

- Cerebrovascular accident or stroke within the past 6 months

- History of hemorrhagic disorders

- No psychiatric disorder precluding understanding of information on trial-related
topics, giving informed consent, filling out quality-of-life forms, or interfering
with compliance for oral drug intake

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy for metastatic or locally recurrent breast cancer

- No prior radiotherapy for metastatic disease

- Prior radiotherapy for the relief of metastatic bone pain allowed provided no
more than 30% of marrow-bearing bone was irradiated

- At least 12 months since prior bevacizumab or other anti-VEGF therapy

- At least 12 months since prior capecitabine, continuous (> 24 hours) fluorouracil
infusion, or other oral fluoropyrimidine (e.g., eniluracil/fluorouracil,
uracil/tegafur, S1, or emitefur)

- At least 12 months since prior taxane-based chemotherapy

- At least 6 months since other prior (neo)adjuvant chemotherapy

- At least 30 days since prior treatment in another clinical trial

- At least 24 hours since prior minor surgical procedures

- At least 28 days since prior and no concurrent major surgical procedures (including
open biopsy) and no anticipation of the need for major surgery during the first
course of this trial

- At least 10 days since prior hormone therapy for metastatic disease

- No continuous daily treatment with corticosteroid except for inhaled steroids

- No concurrent chronic daily aspirin > 325 mg/day

- No concurrent chronic daily clopidogrel > 75 mg/day

- No other concurrent anticancer treatments

- No other concurrent investigational treatments or experimental drugs

- No other concurrent drug therapy contraindicated for use with the trial drugs

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Incidence of grade 3-5 adverse events

Outcome Time Frame:

Documentation of AE observed during trial treatment and in follow-up until resolution

Safety Issue:

Yes

Principal Investigator

Christoph Rochlitz, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Universitaetsspital-Basel

Authority:

Switzerland: Swissmedic

Study ID:

SAKK 24/09

NCT ID:

NCT01131195

Start Date:

June 2010

Completion Date:

October 2015

Related Keywords:

  • Breast Cancer
  • HER2-negative breast cancer
  • recurrent breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • stage IV breast cancer
  • Breast Neoplasms

Name

Location