Bazedoxifene as a Concomitant Treatment of Patients With Metastatic Pancreatic Adenocarcinoma

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT04812808

Studienbeginn:
Februar 2022

Letztes Update:
25.02.2022

Wirkstoff:
Bazedoxifene 20 mg

Indikation (Clinical Trials):
Adenocarcinoma, Pancreatic Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Hôpital Fribourgeois

Collaborator:
-

Studienleiter

Lucie Vignot, MD
Principal Investigator
Hôpital Fribourgeois

Kontakt

Claudia Mellenthin, MD
Kontakt:
Phone: +41 26 306 22 60
E-Mail: dr.mellenthin@hin.ch» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

HFR Fribourg - cantonal hospital
1708 Fribourg
SwitzerlandRekrutierend» Google-Maps
Ansprechpartner:
Lucie Vignot, MD
Phone: +41 26 306 22 60
E-Mail: lucie.vignot@h-fr.ch» Ansprechpartner anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

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

Secondary outcome:

1. Carbohydrate-Antigen 19-9 (CA 19-9) in U/ml (Time Frame - every 3 weeks for 3 months):
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.

2. Change in Quality of life measured by EORTC QLQ-C30 (Time Frame - every 3 weeks for 3 months):
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.

3. Heart rate (bpm) (Time Frame - every 3 weeks for 3 months):
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.

4. Blood pressure (mmHg) (Time Frame - every 3 weeks for 3 months):
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.

5. Oxygen saturation (%) (Time Frame - every 3 weeks for 3 months):
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.

6. weight (kg) (Time Frame - every 3 weeks for 3 months):
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.

7. body temperature (°Celcius) (Time Frame - every 3 weeks for 3 months):
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.

8. liver enzymes (GOT/ASAT in U/l) (Time Frame - every 3 weeks for 3 months):
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.

9. liver enzymes (GPT/ALAT in U/l) (Time Frame - every 3 weeks for 3 months):
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.

10. liver enzymes (GGT in U/l) (Time Frame - every 3 weeks for 3 months):
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.

11. liver enzymes (alkaline phosphatase in U/l) (Time Frame - every 3 weeks for 3 months):
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.

12. liver enzymes (bilirubine in umol/l) (Time Frame - every 3 weeks for 3 months):
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.

13. renal parameters (creatinine in umol/l) (Time Frame - every 3 weeks for 3 months):
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.

14. electrolytes (sodium in mmol/l) (Time Frame - every 3 weeks for 3 months):
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.

15. electrolytes (potassium in mmol/l) (Time Frame - every 3 weeks for 3 months):
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.

16. electrolytes (phosphate in mmol/l) (Time Frame - every 3 weeks for 3 months):
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.

17. electrolytes (calcium in mmol/l) (Time Frame - every 3 weeks for 3 months):
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.

18. Number of patients with adverse events (Time Frame - every 3 weeks for 3 months):
Assess the number of patients with adverse events (according to CTCAE v5.0)

Geprüfte Regime

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.

Quelle: ClinicalTrials.gov

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