Dose-finding Study of BP-C1 in Patients With Stage IV Breast Cancer
Condition: Metastatic Breast Cancer; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to estimate the cumulative Maximum Tolerated Dose (MTD) and
      Minimum Efficient Dose (MED) of BP-C1 in the short-term treatment of metastatic breast cancer
      patients.
    

Detailed description: 
      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.

      In this study BP-C1 will be administered as supportive care to patients with metastatic
      breast cancer (stage IV), who had undergone at least three lines of chemotherapy.

      This study will be open-label, multi-centre with a sequential safety design based on 3-level
      between-patient Response Surface Pathway (RSP) algorithm. The eligible patients will be
      allocated to five independent sequences, with three patients in each sequence. The BP-C1
      treatment period will be 32 days, the follow-up period will be 28 days after the last BP-C1
      dose.
    

Intervention name(s): BP-C1
Intervention type(s): Drug
Intervention description(s): BP-C1, 0.05% solution for injection, will be administered intramuscularly once per day. The cumulative dose range will be 0.64-1.12 mg/kg body weight depending on design level (design level 1-3). The daily dose range will be 0.02-0.035 mg/kg body weight (0.04-0.07 mL/kg) depending on design level (design level 1-3).
Dose level 1: 0.02 mg/kg body weight (0.04 mL/kg) intramuscularly once daily for 32 consecutive days; dose level 2: 0.03 mg/kg body weight (0.06 mL/kg) intramuscularly once daily for 32 consecutive days; dose level 3: 0.035 mg/kg body weight (0.07 mL/kg) intramuscularly once daily for 32 consecutive days.
Changes in the cumulative dose of BP-C1 between patients in the sequence are predefined and will be adjusted by escalation/deescalation rules based on changes in toxicity observed in the previous design level.
The duration of BP-C1 treatment will be 32 days.
Other intervention name(s): Cis-coordinated complexes of platinum(II) with polymer of benzene polycarboxylic acids derived from lignin; Cis-diammineplatinum(II) complexed with a polymer containing benzene polycarboxylic acids derived from lignin
Intervention model: Sequential Assignment
Intervention model description: The study will be open-label, multi-center with a sequential safety design based on 3-level between-patient Response Surface Pathway (RSP) algorithm. Three patients will be recruited consecutively to each sequence of three dose levels (dose level 1 - cumulative dose 0.64 mg/kg body weight, dose level 2 - cumulative dose 0.96 mg/kg body weight, dose level 3 - cumulative dose 1.12 mg/kg body weight).
Masking: None (Open Label)
Primary purpose: Supportive Care
Keywords: BP-C1; Cis-coordinated complexes of platinum(II) with polymer of benzene polycarboxylic acids derived from lignin; Benzene polycarboxylic acids complex with cis-diammineplatinum(II); Metastatic Breast Cancer; Platinum analogue; Metronomic chemotherapy; Breast cancer; Cisplatin; Cis-diammineplatinum(II) complexed with a polymer containing benzene polycarboxylic acids derived from lignin