Clinical trial NCT05372367: A Study in People With Advanced Cancer to Test Whether the Amount of BI 907828 in the Blood is Influenced by Taking an OATP Inhibitor or a CYP3 Inhibitor
Official title: An Open-label Fixed Sequence Trial to Investigate the Potential Drug-drug Interaction When BI 907828 is Co-administered With an OATP1B1 and/or OATP1B3 Transporter Inhibitor or With a CYP3A4 Inhibitor in Patients With Various Solid Tumours
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2022-05-12
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is open for adults with advanced cancer (solid tumours). This is a study for people for whom previous treatment was not successful.

This study tests a medicine called BI 907828. BI 907828 is a so-called MDM2 inhibitor that is being developed to treat cancer. The purpose of this study is to find out whether the amount of BI 907828 in the blood is influenced by taking an OATP inhibitor or a CYP3 inhibitor. This study uses an OATP inhibitor called rifampicin and a CYP3 inhibitor called itraconazole. In clinical practice, rifampicin is used as an antibiotic. Itraconazole is used to treat fungal infections.

Participants are divided into 2 groups: a rifampicin group and an itraconazole group. Every participant takes BI 907828 as a tablet every 3 weeks. This is called a cycle.

* Rifampicin group: In addition to BI 907828, participants take 1 tablet of rifampicin in the second cycle.
* Itraconazole group: In addition to BI 907828, participants take itraconazole tablets for 20 days starting 1 week after the second cycle begins

Participants can stay in the study as long as they benefit from treatment and can tolerate it.

The doctors take blood samples from the participants to compare the amount of BI 907828 in the blood when it is taken alone and when participants also take rifampicin. Doctors also regularly check participants' health and take note of any unwanted effects.


Eligibility criteria: Inclusion criteria:

1. Age ≥18 and ≤70 years.
2. Signed and dated written informed consent in accordance with International Council on Harmonisation - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
3. Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use two medically acceptable methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at screening, during trial participation, and until 6 months and 12 days after last dose for women and 102 days after last dose for men. A list of contraception methods meeting these criteria is provided in the patient information.
4. Patients with histologically or cytologically confirmed diagnosis of advanced, non resectable and/or metastatic solid tumour.
5. Patient with either measurable or non-measurable disease. Non-evaluable disease is allowed.
6. Patient who has failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options. Patient must have exhausted available treatment options known to prolong survival for their disease.
7. Patient has a tumour with either a known Tumor Protein p53 (TP53) wild type status, or unknown TP53 status, at the time of study entry.
8. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1. Further inclusion criteria apply.

Exclusion criteria:

1. Second malignancy currently requiring active therapy (except for hormonal /antihormonal treatment e.g. in prostate or breast cancer).
2. Chemo-, radio- immuno-, or molecular-targeted cancer-therapy within the past four weeks prior to start of BI 907828. This restriction does not apply to steroids, bisphosphonates hormonal / antihormonal treatment (e.g. in prostate or breast cancer).
3. Serious concomitant disease or medical condition which may affect compliance with trial requirements in the opinion of the Investigator.
4. Clinical evidence of active brain metastasis or leptomeningeal disease in the past 6 months prior to screening.
5. Active major infection requiring systemic treatment (antibacterial, antiviral, or antifungal therapy) at treatment start in this trial.
6. Known history of human immunodeficiency virus infection.
7. Patients with a history of Hepatitis C virus (HCV) infection who meet one or both of the following criteria:

   * Currently receiving curative antiviral treatment
   * HCV viral load is above the limit of quantification (HCV RNA positive)
8. Patients with chronic Hepatitis B virus (HBV) infection with active disease who meet the criteria for anti-HBV therapy (according to local / institutional standard) and who have not been treated with suppressive antiviral therapy prior to initiation of study treatment.

Further exclusion criteria apply.

Primary outcomes:
measure: Group 1: Area under the concentration-time curve of BI 907828 in plasma over the time interval from 0 to 24 hours (AUC 0-24)
timeFrame: up to 24 hours
measure: Group 1: Maximum measured concentrations of BI 907828 in plasma (C max)
timeFrame: up to 15 days
measure: Group 2: Area under the concentration-time curve of BI 907828 in plasma over the time interval from 0 to the last quantifiable data point (AUC 0-tz)
timeFrame: up to 15 days
measure: Group 2: Maximum measured concentrations of BI 907828 in plasma (C max)
timeFrame: up to 15 days
Secondary outcomes:
measure: Group 1: Area under the concentration-time curve of BI 907828 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)
timeFrame: up to 15 days
measure: Group 1: Area under the concentration-time curve of BI 907828 in plasma over the time interval from 0 to the last quantifiable data point (AUC 0-tz)
timeFrame: up to 15 days
measure: Group 2: Area under the concentration-time curve of BI 907828 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)
timeFrame: up to 15 days
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Brussels - UNIV Saint-Luc
city: Wilrijk
country: Belgium
facility: Wilrijk - HOSP GZA (St-Augustinus)
city: Barcelona
country: Spain
facility: Hospital Quiron. I.C.U.
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: CIO Clara Campal
city: Madrid
country: Spain
facility: Hospital Quirónsalud Madrid
Study officials:
References: