BP-C1 in Metastatic Breast Cancer Patients

NCT01861509 | Completed Phase 1 DMC

• 1 other identifier: BMC2012-4
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (11)

• 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

  Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose

• 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

  Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose

• 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

  Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose

• 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

  Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose

• 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

  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

• 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

  Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose

• 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

  Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose

• 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

  Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose

• 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

  Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose

• 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

  Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose

• 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

  Pre-dose, 10, 20, 30, 35, 40, 45, 60, 120 min and 6, 24, 48 hours post dose

Secondary Outcomes (4)

• 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)

  Day-1, Day 1, Day 16, Day 32, Day 34

• Change (%) in the sum of diameters of target lesions

  baseline to Day 32 of treatment

• Number of target lesions

  baseline to Day 32 of treatment

• Treatment response

  baseline to Day 32 of treatment

Study Arms (1)

BP-C1 IM Injections

EXPERIMENTAL

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.

Drug: BP-C1

Interventions

BP-C1 DRUG

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

Also known as: 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

BP-C1 IM Injections

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Meabco A/S: lead

Study Sites (2)

Oncology Unit. Sheba Medical Centre

Ramat Gan, 52621, Israel

Location

Lampang Cancer Center

Lampang, 52000, Thailand

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Hydroxyl Radical

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Reactive Oxygen Species; Free Radicals

Study Officials

• Stig Larsen, Prof.

  Meabco A/S

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2013
• First Posted: May 23, 2013
• Study Start: January 19, 2014
• Primary Completion: January 20, 2016
• Study Completion: January 20, 2016
• Last Updated: October 7, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1); IL (1)