Neoadjuvant Treatment With Nab-paclitaxel for Patients With Stage II and III Luminal Breast Cancer

Multicenter, open label, non-randomized phase 2 trial to evaluate the efficacy and safety of nab-paclitaxel in the neoadjuvant treatment of ER positive human epidermal growth factor receptor 2 (HER2) negative patients amenable to receive neoadjuvant chemotherapy.

The primary objective of the trial is to determine the percentage of patients with poor response \[residual cancer burden III (RCB-III) rate\] in contrast to good response \[residual cancer burden 0/I RCB-0/1\] measured by the Symmans criteria \[20\] at surgery, in patients with stage II-III luminal breast cancer treated with neoadjuvant nab-paclitaxel.

The primary endpoint of the study is to determine the residual cancer burden grade III (RCB-III) after surgery.

The total number of patients to be included in this study is 78 patients.

The duration of the study, from first patient visit to last patient visit will be approximately 90 months (Including follow-ups)

Eligibility Criteria:
Inclusion Criteria:

1. Female patients with histologically confirmed diagnosis of primary unilateral invasive early breast cancer with longest tumor size in breast ≥ 2cm, or \< 2 cm with axillary involvement. In case of a multifocal tumor (tumor foci located in the same quadrant) the largest lesion must be ≥ 2cm (unless axillary involvement) and is designated as the "target" lesion for all subsequent tumor evaluations.
2. The breast tumors must be ER positive: more than 1% of stained tumor cells by immuno-histochemistry (IHC), and HER2 negative: 0, or 1+ score by IHC, or 2+ with fluorescence in situ hybridization (FISH)/chromogenic in situ hybridization (CISH) negative for HER2 amplification (defined as a ratio of HER2/neu copies to chromosome 17 centromere (CEP17) signals \<1.8), according to the local laboratory).
3. Are clear candidates to receive chemotherapy by the investigator criteria.
4. Are at least 18 years of age.
5. Have at least one unidimensionally measurable lesion by RECIST \[65\] version 1.1, measured by mammogram.
6. Have adequate performance status: Eastern Cooperative Oncology Group (ECOG) \<2
7. Have adequate renal and liver function and bone marrow reserve as follows:

   * Bone marrow: absolute neutrophil count (ANC) \> or = 1.500/mm3 (1.5 x 109/L); platelet count \> or = 100.000/mm3 (100.0 x 109/L); and hemoglobin \> or = 9 g/dL.
   * Hepatic: bilirubin \< or = 1.5 times the upper limit of normal (x ULN); alkaline phosphatase (ALP), aspartate transaminase (AST), and alanine transaminase (ALT) \< or = 2.5 \* ULN and Albumin ≥ 2.5 g/dL.
   * Renal: serum creatinine \< 1.5 x ULN.
8. Exhibit patient compliance and geographic proximity that allow for adequate follow-up
9. Entry informed consent form signed by the patient.

Exclusion Criteria:

1. Inflammatory breast cancer (T4d) and supraclavicular lymph nodes (N3)
2. Synchronous contralateral or multicentric breast cancer.
3. Clinical or radiologic evidence of metastatic disease. Chest examination by x-ray or CT-scan, abdominal examination by CT-scan, bone examination by bone scan as well as other radiological methods in case of suspicion must be performed before enrollment in order to rule out metastasis.
4. Second primary malignancy, except adequately treated carcinoma in situ of the cervix, stage I colon cancer, non-invasive melanoma, basal or squamous cell carcinomas of the skin, ipsilateral ductal carcinoma in-situ (DCIS) of the breast and lobular carcinoma in-situ (LCIS) of the breast; unless that prior malignancy was diagnosed and definitively treated more than 5 years ago with no subsequent evidence of recurrence.
5. Prior or concurrent anti-cancer therapy for current disease (hormone therapy, chemotherapy, radiotherapy, immunotherapy, biological therapy other than the trial therapies).
6. Concurrent treatment with any hormonal treatment either for osteoporosis or as replacement therapy.
7. Patients with known hypersensitivity to nab-paclitaxel or any of its components.
8. Previous neuropathy grade \>1 according to the NCI-CTCAE vs 4.03 criteria
9. Have received treatment within the last 4 weeks with a drug that has not received regulatory approval for any indication at the time of study entry.
10. Have any serious concomitant systemic disorder incompatible with the study (at the discretion of investigator).
11. Patient is pregnant or breast feeding or planning to become pregnant within the six months after the end of treatment. Women with child-bearing potential must be performed a pregnancy serum or urine testing within 7 days prior to study entry according to institutional standards and should use an adequate non-hormonal contraceptive method (intra-uterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterilized) during treatment with study drugs and within the six months after the end of treatment.