BP-C1 in Short-term Treatment of Patients With Metastatic Breast Cancer

A Randomized, Double Blind and Placebo Controlled Multicenter Study Comparing BP-C1 and Equal Looking Placebo in Metastatic Breast Cancer Patients. A Phase IIB Study

The purpose of this study is to determine whether BP-C1 is effective in the treatment of metastatic breast cancer patients who had previously received at least three lines of chemotherapy.

BP-C1, solution for injection 0.05%, is currently being developed for treatment of patients with metastatic breast cancer with palliative intent. Active substance of the product, which is a novel platinum-containing anticancer agent developed for intramuscular administration, is a cis-diammineplatinum(II) complexed with a polymer containing benzene polycarboxylic acids derived from lignin. The amphiphilic characteristics of the polymer have resulted in a product with clear and significantly altered and improved properties compared to other platinum analogues, e.g. cisplatin, carboplatin and oxaliplatin.

BP-C1 preserves antitumour activity of its predecessors (e.g. cisplatin and carboplatin), additionally offering the following advantages that ensure favourable outcome of treatment of metastatic breast cancer patients:

• injectable solution (intramuscular) does not cause injection site reactions;
• can be administered at home by a nurse or a patient;
• has an improved pharmacokinetic profile;
• demonstrates efficacy comparable to cisplatin and much higher than carboplatin (in-vitro; in-vivo data);
• exerts an additional immunomodulatory activity.

This study is a randomised, double-blind, placebo-controlled, multicentre, phase IIb study. The eligible patients will be allocated (1:1) to either BP-C1 arm or Placebo arm and treated once daily for 32 days. The patients allocated to Placebo arm will cross over to BP-C1 treatment for 32 days when progression of the cancer will be documented and latest after 32-day treatment with Placebo. After 32-day treatment with BP-C1 the patients are invited to participate in the study BMC2011-02 to continue open-label BP-C1 treatment.

Inclusion Criteria:

Female patients with histologically verified metastatic breast cancer (stage IV) with measurable metastases, between 18 and 80 years of age, who had undergone at least three lines of chemotherapy and had an expected survival time of at least 3 months.

Exclusion criteria:

Patients fulfilling at least one of the following criteria will be excluded from participation in the study:

• Abnormal liver function classified as total bilirubin >34 μmol/L or ALAT > 3 times of the upper limit of normal (ULN). In case of metastases in the liver, the ALAT limit for exclusion is set to 5хULN.
• Abnormal kidney function defined by serum creatinine >120 μmol/L.
• Abnormal coagulation capacity defined by the relative arbitrary concentration of coagulation factors 2,7,10; INR >1.5.
• Verified metastases to the brain.
• Synchronous cancer except for non-melanoma skin cancer and early stage of cervical cancer.
• Abnormal hematology status defined by hemoglobin < 9.0 g/dL, platelet count < 100,000/mm^3 or leucocytes < 3 x 10^9/L.
• Clinically significant abnormal ECG.
• Karnofsky performance status score <60%.
• Pregnant or breast feeding women.
• Women of fertile age who do not want to be tested for possible pregnancy.
• Fertile female who do not want to use safe protection against pregnancy, starting one month before the start of the study treatment and lasting at least six weeks after.
• Uncontrolled bacterial, viral, fungal or parasite infection.
• Under systemic treatment with corticosteroids or other immunosuppressive drugs in the last 21 days before start of the trial treatment.
• Participating in another clinical trial with pharmaceuticals in the last six weeks before start of this trial treatment.
• Not able to understand information.
• Not willing or not able to give written consent to participate in the study.