Clinical trial NCT04298333: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: Meabco A/S
Sponsor class: INDUSTRY
Collaborators: name: Meddoc
name: Norwegian University of Life Sciences
name: Meddoc Research Indonesia Ltd
name: Meddoc Research Taiwan Ltd
First posted: 2020-03-06
Enrollment: 18
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Intervention 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).
Primary purpose: SUPPORTIVE_CARE

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.

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.

Primary outcomes:
measure: Change in Maximum Common Terminology Criteria (CTC) score for Adverse Events
timeFrame: baseline to Day 32 of treatment and Day 28 of follow-up
measure: Sum Common Terminology Criteria (CTC) score for Adverse Events
timeFrame: baseline to Day 32 of treatment and Day 28 of follow-up
Secondary outcomes:
measure: Number of registered Adverse Events (AEs)
timeFrame: baseline to Day 32 of treatment period and Day 28 of follow-up
measure: Treatment Response
timeFrame: baseline to Day 32 of treatment and Day 28 of follow-up
measure: Proportion of patients with Disease Control Rate (DCR)
timeFrame: baseline to Day 32 of treatment and Day 28 of follow-up
Other outcomes:
Locations:
city: Bali
country: Indonesia
facility: Sanglah University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital, Mahidol University
Study officials:
References: