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Dose-finding Study of BP-C1 in Patients With Stage IV Breast Cancer

Primary Purpose

Metastatic Breast Cancer, Stage IV Breast Cancer

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

BP-C1

About this trial

This is an interventional supportive care trial for Metastatic Breast Cancer focused on measuring 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

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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 haematology status defined by haemoglobin < 9.0 g/dL, platelet count < 100,000/mm^3 or leucocytes < 3x10^9/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.

Sites / Locations

Sanglah University Hospital
National Taiwan University Hospital
Siriraj Hospital, Mahidol University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BP-C1

Arm Description

BP-C1 will be used as supportive care

Outcomes

Primary Outcome Measures

Change in Maximum Common Terminology Criteria (CTC) score for Adverse Events

Maximum CTC score will be recorded using CTC v2.0 given as the highest observed CTC score at a given visit. The CTC scores will be recorded using CTC v2.0 divided in 15 System Organ Classes

Sum Common Terminology Criteria (CTC) score for Adverse Events

The Sum CTC score will be a sum of all registered CTC scores obtained at a given visit. The CTC scores will be recorded using CTC v2.0 divided in 15 System Organ Classes

Secondary Outcome Measures

Number of registered Adverse Events (AEs)

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.

Proportion of patients with Disease Control Rate (DCR)

The DCR defined as patients classified as SD, PR, CR

Full Information

NCT ID

NCT04298333

First Posted

February 25, 2020

Last Updated

March 4, 2020

Sponsor

Meabco A/S

Collaborators

Meddoc, Norwegian University of Life Sciences, Meddoc Research Indonesia Ltd, Meddoc Research Taiwan Ltd

1. Study Identification

Unique Protocol Identification Number

NCT04298333

Brief Title

Dose-finding Study of BP-C1 in Patients With Stage IV Breast Cancer

Official Title

Estimation of Maximum Tolerable Dose (MTD) and Minimum Efficient Dose (MED) of BP-C1 in Stage IV Breast Cancer Patients: A Phase I Dose-response Study

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Completed

Study Start Date

June 27, 2009 (Actual)

Primary Completion Date

January 4, 2011 (Actual)

Study Completion Date

January 4, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Meabco A/S

Collaborators

Meddoc, Norwegian University of Life Sciences, Meddoc Research Indonesia Ltd, Meddoc Research Taiwan Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

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, 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

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

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)

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BP-C1

Arm Type

Experimental

Arm Description

BP-C1 will be used as supportive care

Intervention Type

Drug

Intervention Name(s)

BP-C1

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 Description

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.

Primary Outcome Measure Information:

Title

Change in Maximum Common Terminology Criteria (CTC) score for Adverse Events

Description

Maximum CTC score will be recorded using CTC v2.0 given as the highest observed CTC score at a given visit. The CTC scores will be recorded using CTC v2.0 divided in 15 System Organ Classes

Time Frame

baseline to Day 32 of treatment and Day 28 of follow-up

Title

Sum Common Terminology Criteria (CTC) score for Adverse Events

Description

The Sum CTC score will be a sum of all registered CTC scores obtained at a given visit. The CTC scores will be recorded using CTC v2.0 divided in 15 System Organ Classes

Time Frame

baseline to Day 32 of treatment and Day 28 of follow-up

Secondary Outcome Measure Information:

Title

Number of registered Adverse Events (AEs)

Time Frame

baseline to Day 32 of treatment period and Day 28 of follow-up

Title

Treatment Response

Description

Time Frame

baseline to Day 32 of treatment and Day 28 of follow-up

Title

Proportion of patients with Disease Control Rate (DCR)

Description

The DCR defined as patients classified as SD, PR, CR

Time Frame

baseline to Day 32 of treatment and Day 28 of follow-up

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 haematology status defined by haemoglobin < 9.0 g/dL, platelet count < 100,000/mm^3 or leucocytes < 3x10^9/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.

Facility Information:

Facility Name

Sanglah University Hospital

City

Bali

Country

Indonesia

Facility Name

National Taiwan University Hospital

City

Taipei

Country

Taiwan

Facility Name

Siriraj Hospital, Mahidol University

City

Bangkok

Country

Thailand

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

http://benthamopen.com/ABSTRACT/TOBCANJ-5-7

Description

Benzene-Poly-Carboxylic Acids Complex with Cis-Diammineplatinum (II) Dichloride in the Treatment of Stage IV Breast Cancer Patients

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Dose-finding Study of BP-C1 in Patients With Stage IV Breast Cancer

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