Clinical trial NCT01861509: BP-C1 in Metastatic Breast Cancer Patients
Official title: Pharmacokinetic, Pharmacodynamic and Interleukin Profile of Intramuscularly Administered BP-C1 in Women With Metastatic Breast Cancer. A Phase ID Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Breast Cancer
Stage IV Breast Cancer
Keywords: BP-C1
Metronomic chemotherapy
Platinum analogue
Cis-diammineplatinum(II) complexed with a polymer containing benzene polycarboxylic acids derived from lignin
Benzene polycarboxylic acids complex with cis-diammineplatinum(II)
Breast cancer
Cisplatin
Metastatic Breast Cancer
Cis-diammineplatinum(II) complex, containing mono-deprotonated benzene-poly-carboxylic acids, derived from lignin, and hydroxyl group as O-donor ligands
Lead sponsor: Meabco A/S
Sponsor class: INDUSTRY
First posted: 2013-05-23
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Single-dose PK: Maximum Observed Serum Concentration (Cmax) for Platinum
timeFrame: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
measure: Single-dose PK: Time to Reach Maximum Observed Serum Concentration (Tmax) for Platinum
timeFrame: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
measure: Single-dose PK: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC(0-t)) for Platinum
timeFrame: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
measure: Single-dose PK: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC(0-∞))
timeFrame: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
measure: Single-dose PK: Serum Decay Half-Life (T1/2) for Platinum
timeFrame: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose during the period of Day-1 to Day 1
measure: Multiple-dose PK: Maximum Observed Serum Concentration at Steady State (Css,max) for Platinum
timeFrame: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
measure: Multiple-dose PK: Time to Reach Maximum Observed Serum Concentration at steady state (Tss,max) for Platinum
timeFrame: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
measure: Multiple-dose PK: Minimum Observed Serum Concentration at Steady State (Css,min) for Platinum
timeFrame: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
measure: Multiple-dose PK: Average Serum concentration at steady state (Css,av) for Platinum
timeFrame: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
measure: Multiple-dose PK: Area Under the Curve within a dosing interval of tau (=24 hr) at steady state (AUCss,tau) for Platinum
timeFrame: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
measure: Multiple-dose PK: Serum Decay Half-Life (T1/2) for Platinum
timeFrame: Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Secondary outcomes:
measure: Interleukin Serum levels (Interferon γ and β, Tumour Necrosis Factor (TNF-α), IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-21 and IL-25)
timeFrame: Day-1, Day 1, Day 16, Day 32, Day 34
measure: Change (%) in the sum of diameters of target lesions
timeFrame: baseline to Day 32 of treatment
measure: Number of target lesions
timeFrame: baseline to Day 32 of treatment
measure: Treatment response
timeFrame: baseline to Day 32 of treatment
Other outcomes:
Locations:
city: Ramat-Gan
country: Israel
facility: Oncology Unit. Sheba Medical Centre
city: Lampang
country: Thailand
facility: Lampang Cancer Center
Study officials:
affiliation: Meabco A/S
name: Stig Larsen, Prof.
role: STUDY_DIRECTOR
References: