Clinical trial NCT03789019: BP-C1 Monotherapy in Patients With Metastatic Breast Cancer Cancer: Estimation of Optimal Duration of Treatment
Official title: Estimation of the Optimal Treatment Duration and Cumulative Dose of BP-C1 in Breast Cancer Patients With Distant Metastases: a Dose-response Study (IC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
First posted: 2018-12-28
Enrollment: 29
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to establish an optimal treatment duration and tolerable cumulative dose for BP-C1 in the treatment of metastatic breast cancer patients who had previously undergone at least three lines of chemotherapy.

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 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 an open-label, non-randomised, single-group, multi-centre study with a sequential safety design. The study consists of two parts: dose-response part and follow-up study.

Dose-response part: Patients who have completed the first 32-day treatment period with BP-C1 from Day 1 to Day 32 under Protocol BMC2011-1/Protocol MBC-BPC1/IIB or Protocol BMC2012-4, and having a maximum of "moderate" toxicity at the end of treatment are offered to continue in the second 32-day treatment period with BP-C1 from Day 33 to Day 64 under protocol BMC2011-02. Patients completing 64-day treatment period with BP-C1 will be followed up for 28 days.

Follow-up study: After 28-day follow-up period the patients without disease progression and without an increase in toxicity are offered to participate in the follow-up study. During the follow-up study the patients will be given BP-C1 as long as they obtain benefit from the treatment (i.e. until disease progression or increase in toxicity not above "moderate" grade).

Eligibility criteria: Inclusion Criteria:

Female patients who have completed 32-day treatment with BP-C1 (under protocols BMC2011-1, MBC-BPC1/IIA, BMC2012-4), having increase in toxicity not above moderate level, and having no progression of the disease. In accordance with inclusion criteria checked in the studies BMC2011-1, MBC-BPC1/IIA, or BMC2012-4, the patients are between 18 and 80 years with metastatic breast cancer (stage IV), had previously underwent at least third line chemotherapy, and have an expected survival time of at least 3 months.

Exclusion Criteria:

* Severe or life-threatening increase in toxicity after preceding 32-day treatment with BP-C1.
* 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 \<0.70 or international normalised ratio (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 3 weeks 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: Sum Common Toxicity Criteria score (Sum CTC score)
timeFrame: baseline to Day 64 of treatment period
measure: Maximum Common Toxicity Criteria score (Maximum CTC score)
timeFrame: baseline to Day 64 of treatment period
Secondary outcomes:
measure: Change (%) in the sum of diameters of target lesions
timeFrame: baseline to Day 64 of treatment period
measure: Treatment response
timeFrame: baseline to Day 64 of treatment period
measure: Karnofsky Performance Status score (KPS score)
timeFrame: baseline to Day 64 of treatment period
measure: Changes in sub-scores of the three major scales of general quality of life questionnaire (EORTC QLQ-C30)
timeFrame: baseline to Day 64 of treatment period
measure: Changes in sub-scores of the specific quality of life questionnaire (EORTC QLQ-BR23)
timeFrame: baseline to Day 64 of treatment period
measure: Number of registered adverse events
timeFrame: baseline to Day 28 of follow-up period
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Russian Oncological Research Centre n.a. N.N. Blokhin, Russian Academy of Medical Science (RAMS)
city: St Petersburg
country: Russian Federation
facility: St. Petersburg State Budgetary Health Organization, City Clinical Oncology Dispensary
city: St. Petersburg
country: Russian Federation
facility: Leningrad Regional Oncological Centre
city: Bangkok
country: Thailand
facility: Siriraj Hospital, Mahidol University
city: Lampang
country: Thailand
facility: Lampang Cancer Hospital
city: Ubon Ratchathani
country: Thailand
facility: Ubon Ratchanthani Cancer Hospital
city: Udon Thani
country: Thailand
facility: Udon Thani Cancer Hospital
Study officials:
affiliation: Meabco A/S
name: Henning Arboe
role: STUDY_CHAIR
References:
citation: 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 Jun 29;7:163. doi: 10.2147/BCTT.S84920.
citation: Lindkaer-Jensen S, Larsen S, Habib-Lindkaer-Jensen N, Fagertun HE. Positive effects on hematological and biochemical imbalances in patients with metastatic breast cancer stage IV, of BP-C1, a new anticancer substance. Drug Des Devel Ther. 2015 Mar 13;9:1481-90. doi: 10.2147/DDDT.S80451. eCollection 2015.