Back to resultsBP-C1 in Metastatic Breast Cancer Patients
Primary Purpose
Metastatic Breast Cancer, Stage IV Breast Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BP-C1
Sponsored by
About this trial
This is an interventional basic science trial for Metastatic Breast Cancer focused on measuring 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
Eligibility Criteria
Inclusion Criteria:
- Female patients with metastatic breast cancer (MBC, stage IV).
- 18 and 80 years of age.
- Measurable lesions / lymph nodes.
- Have previously undergone at least third line chemotherapy.
- Expected survival time at least 3 months.
Exclusion Criteria:
- 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.
- 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.
- 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.
- 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.
- Synchronous cancer except for non-melanoma skin cancer and early stage of cervical cancer.
- 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.
- Clinically significant abnormal ECG.
- Karnofsky Performance Status Score < 50%.
- 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 start of the trial treatment and lasting at least six weeks after.
- Uncontrolled bacterial, viral, fungal or parasite infection.
- 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
- Participating in another clinical trial with pharmaceuticals during the last six weeks before start of this trial treatment.
- Not able to understand written or oral information.
- Do not want or is not able to give written consent to participate in the study.
Sites / Locations
- Oncology Unit. Sheba Medical Centre
- Lampang Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
BP-C1 IM Injections
Arm Description
BP-C1 given in daily intramuscular doses of 0.035 mg/kg bodyweight in one syringe per day during a total treatment of 32 days.
Outcomes
Primary Outcome Measures
Single-dose PK: Maximum Observed Serum Concentration (Cmax) for Platinum
Maximum Observed Serum Concentration (Cmax) for Platinum after the single dose of BP-C1 during the period of Day-1 to Day 1
Single-dose PK: Time to Reach Maximum Observed Serum Concentration (Tmax) for Platinum
Time to Reach Maximum Observed Serum Concentration (Tmax) for Platinum after the single dose of BP-C1 during the period of Day-1 to Day 1
Single-dose PK: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC(0-t)) for Platinum
AUC(0-t) = Area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration after the single dose of BP-C1 during the period of Day-1 to Day 1
Single-dose PK: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC(0-∞))
after the single dose of BP-C1 during the period of Day-1 to Day 1
Single-dose PK: Serum Decay Half-Life (T1/2) for Platinum
Serum decay half-life is the time measured for the serum concentration of Platinum to decrease by one half after the single dose of BP-C1 during the period of Day-1 to Day 1
Multiple-dose PK: Maximum Observed Serum Concentration at Steady State (Css,max) for Platinum
Maximum Observed Serum Concentration at steady state (Css,max) for Platinum during the period of Day 32 to Day 34
Multiple-dose PK: Time to Reach Maximum Observed Serum Concentration at steady state (Tss,max) for Platinum
Time for Css,max at steady state for Platinum during the period of Day 32 to Day 34
Multiple-dose PK: Minimum Observed Serum Concentration at Steady State (Css,min) for Platinum
Minimum Observed Serum Concentration at Steady State (Css,min) for Platinum during the period of Day 32 to Day 34
Multiple-dose PK: Average Serum concentration at steady state (Css,av) for Platinum
Average Serum concentration at steady state (Css,av) for Platinum during the period of Day 32 to Day 34
Multiple-dose PK: Area Under the Curve within a dosing interval of tau (=24 hr) at steady state (AUCss,tau) for Platinum
Area under the serum concentration versus time curve within a dosing interval of tau (=24 hr) at steady state (AUCss,tau) during the period of Day 32 to Day 34
Multiple-dose PK: Serum Decay Half-Life (T1/2) for Platinum
Serum decay half-life is the time measured for the plasma concentration of Platinum to decrease by one half during the period of Day 32 to Day 34
Secondary Outcome Measures
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)
Change (%) in the sum of diameters of target lesions
Diameter of target lesions will be measured by computer tomography (CT) with contrasting using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Number of target lesions
Number of target lesions per each patient will be evaluated by CT with contrasting. Change in number of target lesions from baseline to Day 32 of treatment will be presented in shift tables
Treatment response
In accordance with RECIST v1.1 the treatment response will be classified as 'complete response', 'partial response', 'stable disease' or 'progressive disease': Complete response (CR): disappearance of all target lesions. Partial response (PR): at least 30% decrease in the sum of longest diameters of target lesions, taking as reference the baseline sum of diameters. Progressive disease (PD): at least 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum might also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions will also be considered progression. Stable disease (SD): neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01861509
Brief Title
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
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
January 19, 2014 (Actual)
Primary Completion Date
January 20, 2016 (Actual)
Study Completion Date
January 20, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Meabco A/S
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BP-C1 IM Injections
Arm Type
Experimental
Arm Description
BP-C1 given in daily intramuscular doses of 0.035 mg/kg bodyweight in one syringe per day during a total treatment of 32 days.
Intervention Type
Drug
Intervention Name(s)
BP-C1
Other Intervention Name(s)
Cis-diammineplatinum(II) complexed with a polymer containing benzene polycarboxylic acids derived from lignin, Benzene polycarboxylic acids complex with cis-diammineplatinum(II), Cis-diammineplatinum(II) complex, containing mono-deprotonated benzene-poly-carboxylic acids, derived from lignin, and hydroxyl group as O-donor ligands
Intervention Description
BP-C1, 0.05% solution for injection; doses: 0.035 mg/kg body weight (0.07 mL/kg) intramuscularly once daily for 32 consecutive days
Primary Outcome Measure Information:
Title
Single-dose PK: Maximum Observed Serum Concentration (Cmax) for Platinum
Description
Maximum Observed Serum Concentration (Cmax) for Platinum after the single dose of BP-C1 during the period of Day-1 to Day 1
Time Frame
Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Title
Single-dose PK: Time to Reach Maximum Observed Serum Concentration (Tmax) for Platinum
Description
Time to Reach Maximum Observed Serum Concentration (Tmax) for Platinum after the single dose of BP-C1 during the period of Day-1 to Day 1
Time Frame
Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Title
Single-dose PK: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC(0-t)) for Platinum
Description
AUC(0-t) = Area under the serum concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration after the single dose of BP-C1 during the period of Day-1 to Day 1
Time Frame
Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Title
Single-dose PK: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC(0-∞))
Description
after the single dose of BP-C1 during the period of Day-1 to Day 1
Time Frame
Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Title
Single-dose PK: Serum Decay Half-Life (T1/2) for Platinum
Description
Serum decay half-life is the time measured for the serum concentration of Platinum to decrease by one half after the single dose of BP-C1 during the period of Day-1 to Day 1
Time Frame
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
Title
Multiple-dose PK: Maximum Observed Serum Concentration at Steady State (Css,max) for Platinum
Description
Maximum Observed Serum Concentration at steady state (Css,max) for Platinum during the period of Day 32 to Day 34
Time Frame
Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Title
Multiple-dose PK: Time to Reach Maximum Observed Serum Concentration at steady state (Tss,max) for Platinum
Description
Time for Css,max at steady state for Platinum during the period of Day 32 to Day 34
Time Frame
Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Title
Multiple-dose PK: Minimum Observed Serum Concentration at Steady State (Css,min) for Platinum
Description
Minimum Observed Serum Concentration at Steady State (Css,min) for Platinum during the period of Day 32 to Day 34
Time Frame
Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Title
Multiple-dose PK: Average Serum concentration at steady state (Css,av) for Platinum
Description
Average Serum concentration at steady state (Css,av) for Platinum during the period of Day 32 to Day 34
Time Frame
Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Title
Multiple-dose PK: Area Under the Curve within a dosing interval of tau (=24 hr) at steady state (AUCss,tau) for Platinum
Description
Area under the serum concentration versus time curve within a dosing interval of tau (=24 hr) at steady state (AUCss,tau) during the period of Day 32 to Day 34
Time Frame
Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Title
Multiple-dose PK: Serum Decay Half-Life (T1/2) for Platinum
Description
Serum decay half-life is the time measured for the plasma concentration of Platinum to decrease by one half during the period of Day 32 to Day 34
Time Frame
Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose
Secondary Outcome Measure Information:
Title
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)
Time Frame
Day-1, Day 1, Day 16, Day 32, Day 34
Title
Change (%) in the sum of diameters of target lesions
Description
Diameter of target lesions will be measured by computer tomography (CT) with contrasting using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame
baseline to Day 32 of treatment
Title
Number of target lesions
Description
Number of target lesions per each patient will be evaluated by CT with contrasting. Change in number of target lesions from baseline to Day 32 of treatment will be presented in shift tables
Time Frame
baseline to Day 32 of treatment
Title
Treatment response
Description
In accordance with RECIST v1.1 the treatment response will be classified as 'complete response', 'partial response', 'stable disease' or 'progressive disease': Complete response (CR): disappearance of all target lesions. Partial response (PR): at least 30% decrease in the sum of longest diameters of target lesions, taking as reference the baseline sum of diameters. Progressive disease (PD): at least 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum might also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions will also be considered progression. Stable disease (SD): neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study
Time Frame
baseline to Day 32 of treatment
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female patients with metastatic breast cancer (MBC, stage IV).
18 and 80 years of age.
Measurable lesions / lymph nodes.
Have previously undergone at least third line chemotherapy.
Expected survival time at least 3 months.
Exclusion Criteria:
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.
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.
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.
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.
Synchronous cancer except for non-melanoma skin cancer and early stage of cervical cancer.
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.
Clinically significant abnormal ECG.
Karnofsky Performance Status Score < 50%.
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 start of the trial treatment and lasting at least six weeks after.
Uncontrolled bacterial, viral, fungal or parasite infection.
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
Participating in another clinical trial with pharmaceuticals during the last six weeks before start of this trial treatment.
Not able to understand written or oral information.
Do not want or is not able to give written consent to participate in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stig Larsen, Prof.
Organizational Affiliation
Meabco A/S
Official's Role
Study Director
Facility Information:
Facility Name
Oncology Unit. Sheba Medical Centre
City
Ramat-Gan
ZIP/Postal Code
52621
Country
Israel
Facility Name
Lampang Cancer Center
City
Lampang
ZIP/Postal Code
52000
Country
Thailand
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
BP-C1 in Metastatic Breast Cancer Patients
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