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BP-C1 Monotherapy in Patients With Metastatic Breast Cancer Cancer: Estimation of Optimal Duration of Treatment

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ClinicalTrials.gov Identifier: NCT03789019
Recruitment Status : Completed
First Posted : December 28, 2018
Last Update Posted : October 10, 2019
Sponsor:
Collaborators:
Meddoc
Norwegian University of Life Sciences
Information provided by (Responsible Party):
Meabco A/S

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.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Stage IV Breast Cancer Drug: BP-C1 Phase 2

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).


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: 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)
Actual Study Start Date : February 22, 2013
Actual Primary Completion Date : July 29, 2016
Actual Study Completion Date : July 29, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: BP-C1

Dose-response part: patients who have completed the first 32-day treatment period with BP-C1 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 under the protocol BMC2011-02. Patients completing 64-day treatment period with BP-C1 will be followed up for 28 days.

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).

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-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




Primary Outcome Measures :
  1. Sum Common Toxicity Criteria score (Sum CTC score) [ Time Frame: baseline to Day 64 of treatment period ]
    Toxicity will be assessed according to National Cancer Institute Common Toxicity Criteria version 2.0 (CTC v2.0). The CTC v2.0 is divided in 15 toxicity categories (variables); each category is divided by corresponding sub-variables. Each sub-variable is measured on five-point fixed scale from 0 to 4: 0-none, 1-mild, 2-moderate, 3-severe, 4-life-threatening. However, in this trial each sub-variable will be measured on modified fixed scale from 1 to 4: 1-none or mild, 2-moderate, 3-severe, 4-life-threatening. The classification of each toxicity variable will be judged based on the largest observed value for its sub-variables. The Sum CTC score will be calculated by taking the sum of each variable across all categories.

  2. Maximum Common Toxicity Criteria score (Maximum CTC score) [ Time Frame: baseline to Day 64 of treatment period ]
    Toxicity will be assessed according to National Cancer Institute Common Toxicity Criteria version 2.0 (CTC v2.0). The CTC v2.0 is divided in 15 toxicity categories (variables); each category is divided by corresponding sub-variables. Each sub-variable is measured on five-point fixed scale from 0 to 4: 0-none, 1-mild, 2-moderate, 3-severe, 4-life-threatening. However, in this trial each sub-variable will be measured on modified fixed scale from 1 to 4: 1-none or mild, 2-moderate, 3-severe, 4-life-threatening. The classification of each toxicity variable will be judged based on the largest observed value for its sub-variables. The Maximum CTC score will be calculated by taking the maximum value among all variables across all categories.


Secondary Outcome Measures :
  1. Change (%) in the sum of diameters of target lesions [ Time Frame: baseline to Day 64 of treatment period ]
    Diameter of target lesions will be measured by computer tomography (CT) with contrasting using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  2. Treatment response [ Time Frame: baseline to Day 64 of treatment period ]
    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.

  3. Karnofsky Performance Status score (KPS score) [ Time Frame: baseline to Day 64 of treatment period ]
    KPS score will give an outcome with 11 grades, starting as normal status without complaints and evidence of disease as the best (KPS score = 100) and the dead status as the lowest (KPS score = 0)

  4. Changes in sub-scores of the three major scales of general quality of life questionnaire (EORTC QLQ-C30) [ Time Frame: baseline to Day 64 of treatment period ]
    Quality of life sub-scores will be obtained by general cancer questionnaire EORTC QLQ-C30. EORTC QLQ-C30 consists of 30 questions generally related to cancer. The questionnaire will be self-administered and will be given in patient's mother tongue. EORTC QLQ-C30 (version 3) is divided in the 3 major scales that will be presented as 15 sub-scores: i) global health status; ii) functional scale (physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning); iii) symptom scale/item(fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea, financial difficulties). Range of functional scale is 0-100 (high values are "better"). Range of symptom scale is 0-100 (low values are "better").

  5. Changes in sub-scores of the specific quality of life questionnaire (EORTC QLQ-BR23) [ Time Frame: baseline to Day 64 of treatment period ]
    Quality of life sub-scores will be obtained by specific breast cancer questionnaire EORTC QLQ-BR23. EORTC QLQ-BR-23 consists of 23 questions related to breast cancer. The questionnaire will be self-administered and will be given in patient's mother tongue. EORTC QLQ-BR23 is divided in 2 scales that will be presented as 8 sub-scores: i) functional scale (body image, sexual functioning, sexual enjoyment, future perspective); ii) symptom scale/item (systemic therapy side effect, breast symptom, arm symptom, upset by hair loss). Range of functional scale is 0-100 (high values are "better"). Range of symptom scale is 0-100 (low values are "better").

  6. Number of registered adverse events [ Time Frame: baseline to Day 28 of follow-up period ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03789019


Locations
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Russian Federation
Russian Oncological Research Centre n.a. N.N. Blokhin, Russian Academy of Medical Science (RAMS)
Moscow, Russian Federation
St. Petersburg State Budgetary Health Organization, City Clinical Oncology Dispensary
St Petersburg, Russian Federation
Leningrad Regional Oncological Centre
St. Petersburg, Russian Federation
Thailand
Siriraj Hospital, Mahidol University
Bangkok, Thailand
Lampang Cancer Hospital
Lampang, Thailand, 52000
Ubon Ratchanthani Cancer Hospital
Ubon Ratchathani, Thailand
Udon Thani Cancer Hospital
Udon Thani, Thailand
Sponsors and Collaborators
Meabco A/S
Meddoc
Norwegian University of Life Sciences
Investigators
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Study Chair: Henning Arboe Meabco A/S

Publications of Results:
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Responsible Party: Meabco A/S
ClinicalTrials.gov Identifier: NCT03789019     History of Changes
Other Study ID Numbers: BMC2011-02
First Posted: December 28, 2018    Key Record Dates
Last Update Posted: October 10, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Meabco A/S:
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
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases