BP-C1 in Short-term Treatment of Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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The aim of this study is to investigate the short-term effect and tolerability BP-C1 in patients with metastatic pancreatic cancer who has undergone guideline-recommended chemotherapy.

Detailed Description
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BP-C1, solution for injections 0.05%, is currently being developed for treatment of patients with metastatic breast cancer and metastatic pancreatic cancer with palliative intent. Active substance of the product, which is a novel platinum-containing anticancer agent developed for intramuscular administration, is a complex between cis-diammineplatinum(II) derived core and an amphiphilic polymer, containing a composition of benzene polycarboxylic acids. 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 in metastatic 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; exerts an additional immunomodulatory activity. BP-C2 is a novel lignin-derived polyphenolic composition with ammonium molybdate. BP-C2, given orally, is believed to reduce the toxicity of chemotherapeutic agents. This is a single center, two arm, open label pilot study (phase IIa). The eligible patients will be allocated either to BP-C1 arm or to BP-C1+BP-C2 arm and treated for 32 days with further follow-up for 28 days.

Official Title
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The Effect of BP-C1 in Treatment of Inoperable Pancreatic Cancer Patients: A Single Centre Pilot Study

Conditions
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Metastatic Pancreatic Cancer, Unresectable Pancreatic Cancer

Intervention / Treatment
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* Drug: BP-C1
* Drug: BP-C2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of all genders between 18 and 80 years of age with metastatic pancreatic cancer (unresectable pancreatic cancer with increased levels of cancer antigen 19-9), who 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 >136 μmol/L (8.0 mg/dL) Abnormal kidney function defined by serum creatinine >120 μmol/L (1.5 mg/dL). Abnormal coagulation capacity defined by the relative arbitrary concentration of coagulation factors 2,7,10 < 0.7 or international normalized ratio >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 hemoglobin < 6.0 g/dL, platelet count < 100,000/mm^3 or leucocytes < 3 x 10^9/L. Clinically significant abnormal ECG. Karnofsky performance status score <60%. Pregnancy or breast-feeding. Women of fertile age who do not want to be tested for possible pregnancy. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open label, single center, two arm
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BP-C1<br>Patients will be treated with BP-C1 for 32 consecutive days | Drug: BP-C1<br>* BP-C1, 0.05% solution for injections; doses: 0.035 mg/kg body weight (0.07 mL/kg) intramuscularly once daily for 32 consecutive days<br>* Other names: Benzene polycarboxylic acids complex with cis-diammineplatinum(II);|
| Experimental: BP-C1+BP-C2<br>Patients will be treated with BP-C1 and BP-C2 for 32 consecutive days | Drug: BP-C1<br>* BP-C1, 0.05% solution for injections; doses: 0.035 mg/kg body weight (0.07 mL/kg) intramuscularly once daily for 32 consecutive days<br>* Other names: Benzene polycarboxylic acids complex with cis-diammineplatinum(II);Drug: BP-C2<br>* BP-C2, 0.15% solution for oral use; 15 ml orally once daily for 32 consecutive days<br>* Other names: molybdenum salts of benzene-polycarboxylic acids;|

What is the study measuring?
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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) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 | baseline to Day 32 of treatment | 
| 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 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 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 | 
| Scores of the general quality of life cancer questionnaire (EORTC QLQ-C30) | 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 | 
| 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. | screening to Day 32 of treatment and Day 28 of follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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molybdenum salts of benzene-polycarboxylic acids, Benzene polycarboxylic acids complex with cis-diammineplatinum(II), BP-C1, Cis-coordinated complexes of platinum(II) with polymer of benzene polycarboxylic acids derived from lignin, Platinum analogue, Metronomic chemotherapy, Cisplatin, Pancreatic cancer, BP-C2