BP-C1 in Short-term Treatment of Patients With Metastatic Breast Cancer

A Randomized, Double Blind and Placebo Controlled Multicenter Study Comparing BP-C1 and Equal Looking Placebo in Metastatic Breast Cancer Patients. A Phase IIB Study

The purpose of this study is to determine whether BP-C1 is effective in the treatment of metastatic breast cancer patients who had previously received at least three lines of chemotherapy.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer; Stage IV Breast Cancer
• Intervention / Treatment: Drug: BP-C1; Drug: Placebo

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.

This study is a randomised, double-blind, placebo-controlled, multicentre, phase IIb study. The eligible patients will be allocated (1:1) to either BP-C1 arm or Placebo arm and treated once daily for 32 days. The patients allocated to Placebo arm will cross over to BP-C1 treatment for 32 days when progression of the cancer will be documented and latest after 32-day treatment with Placebo. After 32-day treatment with BP-C1 the patients are invited to participate in the study BMC2011-02 to continue open-label BP-C1 treatment.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Russian Oncological Research Centre n.a. N.N. Blokhin, Russian Academy of Medical Science (RAMS)
  • Nizhniy Novgorod, Russian Federation
    • State Budgetary Institution of Nizhniy Novgorod Region "Oncology Dispensary of Nizhniy Novgorod" (Branch nr.1)
  • St Petersburg, Russian Federation
    • St. Petersburg State Budgetary Health Organization, City Clinical Oncology Dispensary
  • St. Petersburg, Russian Federation
    • Leningrad Regional Oncological Centre
• Thailand
  • Bangkok, Thailand
    • Siriraj Hospital, Mahidol University
  • Udon Thani, Thailand
    • Udon Thani Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Female patients with histologically verified metastatic breast cancer (stage IV) with measurable metastases, between 18 and 80 years of age, who had undergone at least three lines of chemotherapy and had an expected survival time of at least 3 months.

Exclusion criteria:

Patients fulfilling at least one of the following criteria will be excluded from participation in the study:

• Abnormal liver function classified as total bilirubin >34 μmol/L or ALAT > 3 times of the upper limit of normal (ULN). In case of metastases in the liver, the ALAT limit for exclusion is set to 5хULN.
• Abnormal kidney function defined by serum creatinine >120 μmol/L.
• Abnormal coagulation capacity defined by the relative arbitrary concentration of coagulation factors 2,7,10; INR >1.5.
• Verified metastases to the brain.
• Synchronous cancer except for non-melanoma skin cancer and early stage of cervical cancer.
• Abnormal hematology status defined by hemoglobin < 9.0 g/dL, platelet count < 100,000/mm^3 or leucocytes < 3 x 10^9/L.
• Clinically significant abnormal ECG.
• Karnofsky performance status score <60%.
• 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 the start of the study treatment and lasting at least six weeks after.
• Uncontrolled bacterial, viral, fungal or parasite infection.
• Under systemic treatment with corticosteroids or other immunosuppressive drugs in the last 21 days before start of the trial treatment.
• Participating in another clinical trial with pharmaceuticals in the last six weeks before start of this trial treatment.
• Not able to understand information.
• Not willing or not able to give written consent to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BP-C1; Patients randomized to BP-C1 arm will be treated for 32 consecutive days. Patients who respond to treatment and do not experience untolerated toxicity are invited to participate in the BMC2011-02 study, where they will be offered to continue treatment with BP-C1.	Drug: BP-C1; 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; Other Names: Cis-diammineplatinum(II) complexed with a polymer containing benzene polycarboxylic acids derived from lignin; Cis-coordinated complexes of platinum(II) with polymer of benzene polycarboxylic acids derived from lignin
Placebo Comparator: Placebo; Patients randomized to Placebo arm will be treated for 32 consecutive days. Thereafter the patients will cross over to 32-day treatment with BP-C1. Patients who respond to treatment and do not experience untolerated toxicity are invited to participate in the BMC2011-02 study, where they will be offered to continue treatment with BP-C1.	Drug: Placebo; Placebo, solution for injection; doses: 0.07 mL/kg body weight intramuscularly once daily for 32 consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline to Day 32 of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline to Day 32 of treatment
Karnofsky Performance Status (KPS) score	KPS describes an outcome in 11 grades, starting as normal without complaints and evidence of disease (equals 100 as the best) and dead (equals 0) as the lowest. KPS score will be assessed every 16 days during 32-day treatment period.	baseline to Day 16 and Day 32 of treatment
Number of registered adverse events	Adverse events (AEs) will be coded according to the MedDRA (version 16.1E). AEs will be systemized by system organ class and by preferred term. AEs will be analyzed by severity, seriousness and relatedness to the drug.	baseline to Day 32 of treatment
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.	baseline to Day 32 of treatment
Number of non-target lesions	Number of non-target lesions per each patient will be evaluated by CT with contrasting. Change in number of non-target lesions from baseline to Day 32 of treatment will be presented in shift tables.	baseline to Day 32 of treatment
Changes in the scores of the general questionnaire EORTC QLQ-C30 ("Physical activity problem last week", "Discomfort last week", "Health and quality of life")	The EORTC QLQ-C30 is a general quality of life questionnaire for cancer patients. The questionnaire contains 30 questions. Three variables will be obtained from the EORTC QLQ-C30: the sum of scores C1 to C5 denoted as "Physical activity problem last week", the sum of scores C6 to C28 denoted as "Discomfort last week", and the sum of scores C29 and C30 denoted as "Health and quality of life".	baseline to Day 16 and Day 32 of treatment
Changes in three separate scores of the specific questionnaire EORTC QLQ-BR23 ("Breast cancer treatment problem last week", "Sexual interest and activity last four weeks", "Breast cancer related pain and discomfort last week")	The EORTC QLQ-BR23 is a breast cancer-specific quality of life questionnaire. The questionnaire consists of 23 questions. Three variables will be obtained from the EORTC-BR23: the sum of scores BR1 to BR13 denoted as "Breast cancer problem last week", the sum of scores BR14 to BR16 denoted as "Sexual interest and activity last four weeks" and the sum of scores BR17 to BR23 denoted as "Breast cancer related pain and discomfort last week".	baseline to Day 16 and Day 32 of treatment
Change in Maximum Common Toxicity Criteria (CTC) score	Maximum CTC score will be recorded using NCI Common Toxicity Criteria v2.0 divided in 15 categories.	baseline to Day 16 and Day 32 of treatment
Sum CTC score	The Sum CTC score will be a sum of all registered CTC scores by 15 categories.	baseline to Day 16 and Day 32 of treatment

Collaborators and Investigators

• Sponsor: Meabco A/S
• Collaborators: Meddoc; Norwegian University of Life Sciences
• Investigators: Study Director: Steen Lindkær-Jensen, MD, Meabco A/S

Publications and helpful links

General Publications

• Larsen S, Butthongkomvong K, Manikhas A, Trishkina E, Poddubuskaya E, Matrosova M, Srimuninnimit V, Lindkaer-Jensen S. BP-C1 in the treatment of patients with stage IV breast cancer: a randomized, double-blind, placebo-controlled multicenter study and an additional open-label treatment phase. Breast Cancer (Dove Med Press). 2014 Nov 27;6:179-89. doi: 10.2147/BCTT.S71781. eCollection 2014. Erratum In: Breast Cancer (Dove Med Press). 2015;7:163.
• Erratum: BP-C1 in the treatment of patients with stage IV breast cancer: a randomized, double-blind, placebo-controlled multicenter study and an additional open-label treatment phase [Corrigendum]. Breast Cancer (Dove Med Press). 2015 Jun 29;7:163. doi: 10.2147/BCTT.S84920. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: December 24, 2012
• Primary Completion (Actual): February 28, 2014
• Study Completion (Actual): February 28, 2014

Study Registration Dates

• First Submitted: May 18, 2016
• First Submitted That Met QC Criteria: May 25, 2016
• First Posted (Estimate): May 26, 2016

Study Record Updates

• Last Update Posted (Actual): October 10, 2019
• Last Update Submitted That Met QC Criteria: October 8, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Cisplatin; Breast cancer; Metronomic chemotherapy; Metastatic Breast Cancer; BP-C1; Platinum analogue; Cis-diammineplatinum(II) complexed with a polymer containing benzene polycarboxylic acids derived from lignin; Benzene polycarboxylic acids complex with cis-diammineplatinum(II); Cis-coordinated complexes of platinum(II) with polymer of benzene polycarboxylic acids derived from lignin
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: BMC2011-1