Pilot Study to Evaluate Reparixin With Weekly Paclitaxel in Patients With HER 2 Negative Metastatic Breast Cancer (MBC)

• Status: Completed
• Trial end date: 2015-01-15
• Target enrollment: 0
• Participant gender: Female

Summary

This is a phase I study to evaluate the safety and define the pharmacokinetic (PK) profile of orally administered reparixin in combination with paclitaxel in HER 2 (Human epidermal growth factor receptor-2) negative metastatic breast cancer patients.

The primary objective of this study was to evaluate the safety and define the pharmacokinetic (PK) profile of orally administered reparixin in combination with paclitaxel in HER-2 negative MBC patients.

The secondary objectives were to:

1. Evaluate the effects of orally administered reparixin on cancer stem cell (CSC) markers, the tumoral microenvironment and markers of cytokine inflammation;

2. Evaluate peripheral blood samples for enumeration of circulating tumor cells (CTCs), molecular characterization as CSCs and perform epithelial-mesenchymal transition (EMT) biomarker profiling;

3. Assess disease response for indication of efficacy.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dompé Farmaceutici S.p.A
• Collaborator: PRA Health Sciences
• Treatments: Albumin-Bound Paclitaxel; Paclitaxel

Criteria

Inclusion Criteria:

1. Female aged ≥ 18 years.

2. Patients with histologic or cytologic diagnosis of breast cancer with evidence of metastatic disease with documented HER-2 negative status and eligible for treatment with paclitaxel.

3. Patients with at least one baseline measurable lesion according to RECIST version 1.1 criteria.

4. Zubrod (Eastern Co-operative Oncology Group [ECOG]) Performance Status (PS) of 0-1.

5. An electrocardiogram (ECG) with no clinically significant abnormalities indicative of myocardial ischemia.

6. Ongoing toxicity associated with prior anticancer therapy ≤ grade 1 Common Terminology Criteria for Adverse Events (CTCAE version 4.03) with the exception of alopecia.

7. Maximum of three prior chemotherapy lines for advanced breast cancer (not including neo/adjuvant chemotherapy). If prior treatment with paclitaxel, PD must have occurred > 12 months from the end of previous adjuvant treatment or for previous metastatic treatment no PD must have occurred during treatment or within 3 months of the end of treatment

8. Life expectancy of at least three months.

9. Patients must be able to swallow and retain oral medication (intact tablet).

10. Able to undergo all screening assessments outlined in the protocol following written informed consent.

11. Adequate organ function (defined by the following parameters):

1. Serum creatinine < 140 µmol/L or creatinine clearance > 60 mL/min.

2. Serum hemoglobin ≥ 9 g/dL; absolute neutrophil count ≥ 1.5 x 10**9/L; platelets ≥ 100 x 10**9/L.

3. Serum bilirubin ≤ 1.5 x upper normal limit (UNL).

4. Serum ALT, AST ≤ 2.5 x UNL but ≤ 5.0 x UNL in case of liver metastases; ALP ≤ UNL but ≤ 1.5 x ULN in case of liver metastases; albumin within normal limits. If ALP is greater than 1.5 x UNL (in the presence of liver metastases) the liver isoenzyme fraction will be measured. Liver isoenzyme fraction (absolute value) must be ≤ 1.5 x UNL.

12. No known hepatitis B virus (not due to immunization), hepatitis C virus, human immunodeficiency virus Ι and -ΙΙ positive status.

Exclusion Criteria:

1. Male.

2. Pregnancy or lactation or unwillingness to use adequate method of birth control.

3. HER-2 positive disease status.

4. Less than four weeks since last chemotherapy, radiotherapy or prior investigational therapy. Less than two weeks since last hormone or immunotherapy or signal transduction therapy.

5. Neurological or psychiatric disorders which may influence understanding of study and informed consent procedures.

6. Active or uncontrolled infection.

7. Malabsorption syndrome, disease significantly affecting gastrointestinal function.

8. Hypersensitivity to:

1. paclitaxel

2. ibuprofen or to more than one non-steroidal anti-inflammatory drug.

3. medications belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib.

9. Presence of brain metastases (this does not include primary brain tumors) or leptomeningeal disease.