Clinical trial NCT04812808: Bazedoxifene as a Concomitant Treatment of Patients With Metastatic Pancreatic Adenocarcinoma
Official title: Bazedoxifene as a Concomitant Treatment of Patients With Metastatic Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pancreas Cancer
Lead sponsor: Hôpital Fribourgeois
Sponsor class: OTHER
First posted: 2021-03-24
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in IL-6/GP-130/STAT3 pathway expression (%)
timeFrame: 3 months
Secondary outcomes:
measure: Carbohydrate-Antigen 19-9 (CA 19-9) in U/ml
timeFrame: every 3 weeks for 3 months
measure: Change in Quality of life measured by EORTC QLQ-C30
timeFrame: every 3 weeks for 3 months
measure: Heart rate (bpm)
timeFrame: every 3 weeks for 3 months
measure: Blood pressure (mmHg)
timeFrame: every 3 weeks for 3 months
measure: Oxygen saturation (%)
timeFrame: every 3 weeks for 3 months
measure: weight (kg)
timeFrame: every 3 weeks for 3 months
measure: body temperature (°Celcius)
timeFrame: every 3 weeks for 3 months
measure: liver enzymes (GOT/ASAT in U/l)
timeFrame: every 3 weeks for 3 months
measure: liver enzymes (GPT/ALAT in U/l)
timeFrame: every 3 weeks for 3 months
measure: liver enzymes (GGT in U/l)
timeFrame: every 3 weeks for 3 months
measure: liver enzymes (alkaline phosphatase in U/l)
timeFrame: every 3 weeks for 3 months
measure: liver enzymes (bilirubine in umol/l)
timeFrame: every 3 weeks for 3 months
measure: renal parameters (creatinine in umol/l)
timeFrame: every 3 weeks for 3 months
measure: electrolytes (sodium in mmol/l)
timeFrame: every 3 weeks for 3 months
measure: electrolytes (potassium in mmol/l)
timeFrame: every 3 weeks for 3 months
measure: electrolytes (phosphate in mmol/l)
timeFrame: every 3 weeks for 3 months
measure: electrolytes (calcium in mmol/l)
timeFrame: every 3 weeks for 3 months
measure: Number of patients with adverse events
timeFrame: every 3 weeks for 3 months
Other outcomes:
Locations:
city: Fribourg
country: Switzerland
facility: HFR Fribourg - cantonal hospital
Study officials:
affiliation: Hôpital Fribourgeois
name: Lucie Vignot, MD
role: PRINCIPAL_INVESTIGATOR
References: