Bazedoxifene as a Concomitant Treatment of Patients With Metastatic Pancreatic Adenocarcinoma (BAZE)

Bazedoxifene, a selective estrogen receptor modulator is thought to have effective anti-tumoral properties for pancreatic cancer via IL-6 pathway (GP130/STAT3) inhibition.

The objective is to measure IL-6 (GP130/STAT3)-pathway modification on metastasis biopsy of patients with metastatic pancreatic adenocarcinoma before and after treatment with bazedoxifene in addition to chemotherapy.

This study is a single-center, prospective, nonrandomized trial.

Study Overview

• Status: Recruiting
• Conditions: Pancreas Cancer
• Intervention / Treatment: Drug: Bazedoxifene 20 mg

Detailed Description

This study is a single-center, prospective, non-randomized trial. The population studied will consist of 10 patients of both sexes, aged 18 to 85 years, with a newly diagnosed metastatic pancreatic adenocarcinoma who will undergo palliative treatment with standard first line chemotherapy (Gemcitabine +/- Nab-paclitaxel). Diagnosis must be confirmed by biopsy and metastasis must be accessible for percutaneous biopsy using imaging guidance. Further, only patients with an IL-6 (GP130/STAT3)-pathway activity of more than 5% on diagnostic biopsy will be included .

In addition to chemotherapy, patients will receive 20 mg bazedoxifene (Conbriza®) orally per day, subject to good clinical tolerance and in the absence of a biological contraindication.

Patients will receive bazedoxifene once a day at any time, with or without meals. Initiation of treatment will be simultaneous to the initiation of chemotherapy. Bazedoxifene (Conbriza®) will be prescribed and administered for the duration of the study. To minimize the risk of thrombo-embolic events, prophylactic rivaroxaban (Xarelto®) 10 mg orally once per day will be added for the duration of the bazedoxifene (Conbriza®) intake. Pantoprazole 20 mg once per day will be added in selected patients to minimize gastric complications according to the physician's appreciation. Participants will receive bazedoxifene (Conbriza®) and rivaroxaban (Xarelto®) for the entire study duration from a subinvestigator at treatment initiation visit.

Physical examination with vital parameters, laboratory testing (blood count, liver enzymes, creatinine) and tumor marker (CA 19-9) will be conducted in order to determine the baseline prior to the initiation of the treatment. The quality of life using the EORTC core quality of life questionnaire (QLQ-C30) will also be assessed at that point. Furthermore, the IL-6 pathway activity (GP130/STAT3) will be assessed immunohistochemically on metastasis biopsy before administration of bazedoxifene (Conbriza®). The tissue will be obtained by percutaneous biopsy using imaging guidance. A biopsy performed before study inclusion can be used as baseline to avoid a second biopsy.

Study enrollment and follow-up will be performed by the consultant physician at the HFR Fribourg in the department of oncology. The follow-up will be carried out every 3 to 4 weeks and will consist of a physical examination, vital parameters, laboratory testing (blood count, liver enzymes, creatinine, electrolytes) and tumor marker (CA 19-9). Plasma samples will be collected before and after treatment for storage and samples will be analyzed through next generation sequencing NGS. Quality-of-life will be assessed during the follow-ups and drug adherence will be monitored through patient survey.

After 3 months of treatment, the primary endpoint will be assessed. Thoraco-abdominal CT scan or PET-CT will be performed, and a biopsy of metastasis tissue will be repeated (percutaneous under radiological guidance) for immunohistochemical IL-6 pathway activity (GP130/STAT3) analysis. The activity of bazedoxifene (Conbriza®) on inflammatory pathways and tumor progression will be evaluated by comparing the modification in expression of the IL-6 pathway (GP130/STAT3) from baseline.

Patients will be instructed by the investigator to report the occurrence of any adverse event.

The expected duration of the study for each participant will be 12 to 16 weeks.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Claudia Mellenthin, MD; Phone Number: +41 26 306 22 60; Email: dr.mellenthin@hin.ch

Study Locations

• Switzerland
  • Fribourg, Switzerland, 1708
    • Recruiting
    • HFR Fribourg - Cantonal Hospital
    • Contact: Lucie Vignot, MD; Phone Number: +41 26 306 22 60; Email: lucie.vignot@h-fr.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults aged from 18 to 85,
• Newly diagnosed metastatic pancreatic adenocarcinoma (stage IV according to AJCC)
• Accessible metastasis for percutaneous biopsy using imaging guidance
• IL-6 (GP130/STAT3)-pathway activity of more than 5% on diagnostic biopsy will be included
• Palliative chemotherapy planned,
• Informed Consent as documented by signature (Appendix Informed Consent Form).

Exclusion Criteria:

• No treatment for pancreatic adenocarcinoma,
• Curative treatment of pancreatic adenocarcinoma,
• No accessible metastasis for biopsy,
• Previous thrombo-embolic events,
• Known hypersensibility or allergy to bazedoxifene or one of the Conbriza excipient,
• Women who are pregnant or breast feeding,
• Intention to become pregnant during the course of the study,
• Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases. Female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of childbearing potential.
• Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.),
• Known or suspected non-compliance, drug or alcohol abuse,
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
• Inability to give informed consent,
• Participation in another study with investigational drug within the 30 days preceding and during the present study,
• Previous enrolment into the current study,
• Enrolment of the investigator, his/her family members, employees and other dependent persons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bazedoxifene administered in addition to standard chemotherapy protocol	Drug: Bazedoxifene 20 mg; Bazedoxifene will be administered during the duration of the study in the experimental arm together with chemotherapy. Prophylactic rivaroxaban (Xarelto®) 10 mg per day orally will be added to avoid thromboembolic events.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in IL-6/GP-130/STAT3 pathway expression (%)	Assessment of IL-6 (GP130/STAT3) activity by immunohistochemistry on metastasis biopsy before and after treatment with bazedoxifene in addition to chemotherapy.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Carbohydrate-Antigen 19-9 (CA 19-9) in U/ml	The change in tumor marker CA 19-9 as a reflection of tumor progression. CA 19-9 will be measured on blood samples collected every 3 to 4 weeks throughout the trial and compared with the baseline prior to treatment initiation.	every 3 weeks for 3 months
Change in Quality of life measured by EORTC QLQ-C30	Quality of life using the quality-of-life questionnaire EORTC QLQ-C30. This variable will be measured every 3 to 4 weeks throughout the trial and compared with the baseline prior to treatment initiation. Score ranging from 0 to 100. High scale score represents a higher response level.	every 3 weeks for 3 months
Heart rate (bpm)	Assess toxicity of bazedoxifene in combination with chemotherapy. Physical examination will be performed and blood samples, including renal and hepatic parameters, will be analyzed every 3 to 4 weeks.	every 3 weeks for 3 months
Blood pressure (mmHg)	Assess toxicity of bazedoxifene in combination with chemotherapy. Physical examination will be performed and blood samples, including renal and hepatic parameters, will be analyzed every 3 to 4 weeks.	every 3 weeks for 3 months
Oxygen saturation (%)	Assess toxicity of bazedoxifene in combination with chemotherapy. Physical examination will be performed and blood samples, including renal and hepatic parameters, will be analyzed every 3 to 4 weeks.	every 3 weeks for 3 months
weight (kg)	Assess toxicity of bazedoxifene in combination with chemotherapy. Physical examination will be performed and blood samples, including renal and hepatic parameters, will be analyzed every 3 to 4 weeks.	every 3 weeks for 3 months
body temperature (°Celcius)	Assess toxicity of bazedoxifene in combination with chemotherapy. Physical examination will be performed and blood samples, including renal and hepatic parameters, will be analyzed every 3 to 4 weeks.	every 3 weeks for 3 months
liver enzymes (GOT/ASAT in U/l)	Assess toxicity of bazedoxifene in combination with chemotherapy. Physical examination will be performed and blood samples, including renal and hepatic parameters, will be analyzed every 3 to 4 weeks.	every 3 weeks for 3 months
liver enzymes (GPT/ALAT in U/l)	Assess toxicity of bazedoxifene in combination with chemotherapy. Physical examination will be performed and blood samples, including renal and hepatic parameters, will be analyzed every 3 to 4 weeks.	every 3 weeks for 3 months
liver enzymes (GGT in U/l)	Assess toxicity of bazedoxifene in combination with chemotherapy. Physical examination will be performed and blood samples, including renal and hepatic parameters, will be analyzed every 3 to 4 weeks.	every 3 weeks for 3 months
liver enzymes (alkaline phosphatase in U/l)	Assess toxicity of bazedoxifene in combination with chemotherapy. Physical examination will be performed and blood samples, including renal and hepatic parameters, will be analyzed every 3 to 4 weeks.	every 3 weeks for 3 months
liver enzymes (bilirubine in umol/l)	Assess toxicity of bazedoxifene in combination with chemotherapy. Physical examination will be performed and blood samples, including renal and hepatic parameters, will be analyzed every 3 to 4 weeks.	every 3 weeks for 3 months
renal parameters (creatinine in umol/l)	Assess toxicity of bazedoxifene in combination with chemotherapy. Physical examination will be performed and blood samples, including renal and hepatic parameters, will be analyzed every 3 to 4 weeks.	every 3 weeks for 3 months
electrolytes (sodium in mmol/l)	Assess toxicity of bazedoxifene in combination with chemotherapy. Physical examination will be performed and blood samples, including renal and hepatic parameters, will be analyzed every 3 to 4 weeks.	every 3 weeks for 3 months
electrolytes (potassium in mmol/l)	Assess toxicity of bazedoxifene in combination with chemotherapy. Physical examination will be performed and blood samples, including renal and hepatic parameters, will be analyzed every 3 to 4 weeks.	every 3 weeks for 3 months
electrolytes (phosphate in mmol/l)	Assess toxicity of bazedoxifene in combination with chemotherapy. Physical examination will be performed and blood samples, including renal and hepatic parameters, will be analyzed every 3 to 4 weeks.	every 3 weeks for 3 months
electrolytes (calcium in mmol/l)	Assess toxicity of bazedoxifene in combination with chemotherapy. Physical examination will be performed and blood samples, including renal and hepatic parameters, will be analyzed every 3 to 4 weeks.	every 3 weeks for 3 months
Number of patients with adverse events	Assess the number of patients with adverse events (according to CTCAE v5.0)	every 3 weeks for 3 months

Collaborators and Investigators

• Sponsor: Hôpital Fribourgeois
• Investigators: Principal Investigator: Lucie Vignot, MD, Hôpital Fribourgeois

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Anticipated): January 31, 2024
• Study Completion (Anticipated): May 31, 2024

Study Registration Dates

• First Submitted: March 12, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (Actual): March 24, 2021

Study Record Updates

• Last Update Posted (Actual): February 25, 2022
• Last Update Submitted That Met QC Criteria: February 9, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Adenocarcinoma; Pancreatic Neoplasms; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Bone Density Conservation Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Bazedoxifene
• Other Study ID Numbers: Grant-2104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No