BP-C1 in Metastatic Breast Cancer Patients

Pharmacokinetic, Pharmacodynamic and Interleukin Profile of Intramuscularly Administered BP-C1 in Women With Metastatic Breast Cancer. A Phase ID Study

This study is an open label, non-randomized phase I single-armed study in women with metastatic breast cancer (MBC) who have previously undergone all available standard chemotherapy regimens. The purpose of the study is to estimate the pharmacokinetics (PK) after single dose and multiple dose of BP-C1, investigate interleukin levels during BP-C1 treatment and assess treatment response according to RECIST criteria.

BP-C1, solution for injections 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 а 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.

In this study six female patients with MBC who have previously undergone at least third line therapy will be enrolled. Each included patient will participate in a screening period (maximum duration of 21 days) following by 32-day treatment period and 28-day follow-up period.

The patients will be treated with BP-C1(daily intramuscular injections) for 32 consecutive days. The study is undertaken to evaluate pharmacokinetics, pharmacodynamics and treatment effect of BP-C1.

Inclusion Criteria:

1. Female patients with metastatic breast cancer (MBC, stage IV).
2. 18 and 80 years of age.
3. Measurable lesions / lymph nodes.
4. Have previously undergone at least third line chemotherapy.
5. Expected survival time at least 3 months.

Exclusion Criteria:

1. Abnormal liver function classified as total bilirubin >34 μmol/L or ALAT > 3 times the upper limit of normal range (ULN). In case of metastases in the liver, the ALAT limit for exclusion is set to 5xULN. Re-test results of blood samples taken again up to 2 days before Day-1 must keep meeting eligibility criteria.
2. Abnormal kidney function defined by serum creatinine >120 μmol/L. Re-test results of blood samples taken again up to 2 days before Day-1 must keep meeting eligibility criteria.
3. Abnormal coagulation capacity defined by the relative arbitrary concentration of coagulation factors 2,7,10 INR >1.3. Re-test results of blood samples taken again up to 2 days before Day-1 must keep meeting eligibility criteria.
4. Brain metastases in symptomatic patients requiring ≥4 mg dexamethasone/day. However, patients with treated brain metastases by surgery or radiation who are stable and symptom-free (<4 mg dexamethasone/day) for a minimum period of 4 weeks prior to study treatment are eligible.
5. Synchronous cancer except for non-melanoma skin cancer and early stage of cervical cancer.
6. Abnormal haematology status defined by Hb < 9.0 g/dL, platelet count < 75,000/mm^3 and leukocytes < 3x10^9/L. Re-test results of blood samples taken again up to 2 days before Day-1 must keep meeting eligibility criteria.
7. Clinically significant abnormal ECG.
8. Karnofsky Performance Status Score < 50%.
9. Pregnant or breast feeding women.
10. Women of fertile age who do not want to be tested for possible pregnancy.
11. Fertile female who do not want to use safe protection against pregnancy, starting one month before start of the trial treatment and lasting at least six weeks after.
12. Uncontrolled bacterial, viral, fungal or parasite infection.
13. Under systemic treatment with corticosteroids or other immunosuppressive drugs during the last 21 days before start of the trial treatment. Systemic treatment with <4 mg dexamethasone/day is allowed
14. Participating in another clinical trial with pharmaceuticals during the last six weeks before start of this trial treatment.
15. Not able to understand written or oral information.
16. Do not want or is not able to give written consent to participate in the study.