Studieoverzicht - 2010-02 STOP&GO

Randomization:

Arm A: patients will receive 8 continuous cycles of chemotherapy in first and second line treatment.
Arm B: patients will receive 8 cycles of intermittent (2 times 4 cycles) chemotherapy in first and second line treatment.

In first line treatment, patients in both study arms will receive paclitaxel and bevacizumab continued with bevacizumab only until Progressive Disease (PD) or unacceptable toxicity, whichever comes first.

As second line treatment patients will receive non-pegylated liposomal doxorubicin.

Primary:

• To demonstrate that the progression-free survival (PFS) of 8 cycles of intermittent (2 times 4 cycles) chemotherapy (paclitaxel) is not inferior in efficacy, compared to 8 continuous cycles of chemotherapy (paclitaxel), both in combination with bevacizumab, in first line treatment of patients with HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer.

Secondary:

• To compare the PFS of second line treatment of 8 continuous cycles of chemotherapy with liposomal doxorubicin (or capecitabine) with 8 cycles of intermittent (2 times 4 cycles) chemotherapy with liposomal doxorubicin (or capecitabine);
• To compare the objective Overall Response Rate (ORR) between 8 continuous cycles of chemotherapy with 8 cycles of intermittent (2 times 4 cycles) chemotherapy in first treatment line, combined with bevacizumab, and in second treatment line;
• To compare the Duration of Objective Response (DOR) between 8 continuous cycles of chemotherapy with 8 cycles of intermittent (2 times 4 cycles) chemotherapy in first treatment line, combined with bevacizumab, and second treatment line; For the intermittent chemotherapy schedule the first DOR and, if applicable, second DOR in the same treatment line will be accumulated;
• To compare Overall Survival (OS) between 8 continuous cycles of chemotherapy with 8 cycles of intermittent (2 times 4 cycles) chemotherapy;
• To compare the Safety between 8 continuous cycles of chemotherapy with 8 cycles of intermittent (2 times 4 cycles) chemotherapy;
• To compare the Quality of Life (QoL) between 8 continuous cycles of chemotherapy with 8 cycles of intermittent (2 times 4 cycles) chemotherapy
• To compare the Pharmacoeconomics between 8 continuous cycles of chemotherapy with 8 cycles of intermittent (2 times 4 cycles) chemotherapy.

 Primary endpoint:

• PFS is defined as the time from start of treatment to the documented progression that requires the patient to switch to the next treatment line or to death due to any cause.

Secondary endpoints:

• Changes in the RAND 36 quality of life scale will be measured.
• Safety and tolerability.

Other:

• ORR calculated as the proportion of patients with a best overall response of confirmed Complete Response (CR) and Partial Response (PR).
• DOR calculated as the time from the date of first documented CR or PR to the first documented progression or death due to underlying cancer.
• OS calculated as the time from the date of randomization to the date of death due to any cause or the date of last contact.
• Direct medical costs will be calculated using a standard cost method.

• 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 disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria as determined by the investigator.
• Documented Estrogen Receptor (ER) / Progesteron Receptor (PR) status.
• HER2/neu-negative disease as determined by immunohistochemistry or Fluorescence In Situ Hybridization (FISH).
• Patients with an ECOG Performance Status ≤ 2.
• Life expectancy of >=12 weeks.
• Signature of Informed Consent Form by patient

BOOG 2010-02 Stop&Go Protocol synopsis vs 3 20121127