Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

This Study Aims to Find the Best Dose of BI 907828 in Patients With Different Types of Advanced Cancer (Solid Tumors)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03449381
Recruitment Status : Recruiting
First Posted : February 28, 2018
Last Update Posted : June 16, 2022
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

This study is open to adults with different types of advanced cancer (solid tumors). The purpose of this study is to find out the most suitable dose of BI 907828 the participants can tolerate. The most suitable dose is used in the second part to find out whether BI 907828 makes tumors shrink.

In this study, BI 907828 is given to humans for the first time. BI 907828 is a so-called MDM2 inhibitor that is being developed to treat cancer. BI 907828 is taken as a tablet. Participants either take a dose of BI 907828 on one day every 3 weeks or on two days every 4 weeks.

The participants are in the study for as long as they benefit from and can tolerate treatment. The doctors regularly check the participants' general health during the study.


Condition or disease Intervention/treatment Phase
Neoplasms Drug: BI 907828 Phase 1

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 204 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ia/Ib, Open Label, Multicenter, Dose-escalation Study of BI 907828 in Patients With Advanced or Metastatic Solid Tumors
Actual Study Start Date : May 21, 2018
Estimated Primary Completion Date : March 31, 2026
Estimated Study Completion Date : April 30, 2026
Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Dose Escalation Drug: BI 907828
Film-coated tablet
Experimental: Dose Expansion Drug: BI 907828
Film-coated tablet


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Phase Ia- Maximum tolerated dose (MTD) based on number of patients with dose limiting toxicities (DLTs) during first treatment cycle [ Time Frame: Up to 28 days ]
  2. Progression-free survival [ Time Frame: Up to 24 months ]
  3. Phase Ia - Number of patients with DLTs during first treatment cycle (21 days, Arm A; 28 days, Arm B) [ Time Frame: Up to 28 days ]
  4. Phase Ib - Number of patients with DLTs during the first treatment cycle [ Time Frame: Up to 28 days ]

Secondary Outcome Measures :
  1. Phase Ia - Cmax: Maximum measured concentration of BI 907828 in plasma [ Time Frame: Up to 24 months ]
  2. Phase Ia - AUC0-∞: Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity [ Time Frame: Up to 24 months ]
  3. Phase Ib - Objective response [ Time Frame: Up to 24 months ]
  4. Phase Ib - Overall survival [ Time Frame: Up to 24 months ]
  5. Phase Ib - Number of patients with Grade ≥3 treatment-related adverse events observed during the entire treatment period [ Time Frame: Up to 24 months ]
  6. Phase Ib - Cmax: Maximum measured concentration of BI 907828 in plasma [ Time Frame: Up to 24 months ]
  7. Phase Ib - AUC0-∞: Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity [ Time Frame: Up to 24 months ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provision of signed and dated, written informed consent form ICF in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses.
  • Pathologically documented, advanced solid tumors.
  • Radiologically documented disease progression or relapse. Patients who are not eligible to receive standard of care treatments, and for whom no proven treatments exist, are eligible.
  • Patients with mouse double minute 2 homolog (MDM2) amplified sarcomas who require first line treatment (for Ph Ib/dose expansion - Cohort 1 only).
  • Patients with MDM2 amplified sarcomas may fulfil any one of the above three criteria to be considered eligible.

  • Phase Ia (dose escalation) only:

    --Patient has a tumor with either a known tumor protein P53 (TP53) wild type (wt) status, or unknown TP53 status, and regardless of MDM2 amplification status, at the time of study entry.

  • Phase Ib (expansion phase) only:

    • Cohort 1: TP53 wt and MDM2-non-amplified solid tumors
    • Cohort 2: TP53 wt and MDM2- amplified solid tumors.

  • Phase Ia (dose escalation) only:

    • Patient with either measurable or non-measurable disease.
    • Non-evaluable disease allowed.

  • Phase Ib (expansion phase) only:

    --At least one target lesion that can be accurately measured per RECIST v.1.1.

  • Patient must be willing to submit the blood sampling for the pharmacokinetics (PK), pharmacodynamics (PD), biomarker, and pharmacogenetics (PGx) analyses.
  • Availability and willingness to provide a fresh tumor tissue sample obtained after relapse or progression during or after prior therapy. In case a fresh biopsy cannot be obtained (e.g. inaccessible lesions or patient safety concern), an archived specimen, collected before screening, may be submitted. If these requirements cannot be met, then the patient may be allowed to enter the study at Sponsor discretion, after agreement between the Investigator and Sponsor.
  • Male or female ≥18 years old (for Japan, ≥20 years old) at the time of signature of the informed consent form (ICF)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (an ECOG of 2 is acceptable, if it is due to noncancer-related disability, and after agreement with Sponsor).
  • Life expectancy of at least 12 weeks after the start of the treatment according to the Investigator's judgement.
  • Adequate organ function
  • Male or female patients. Women of childbearing potential (WOCBP) a woman is considered a WOCBP, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. Tubal ligation is NOT a method of permanent sterilization. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. Men able to father a child and women of WOCBP 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.

Exclusion Criteria:

  • Previous administration of BI 907828 or any other MDM2-p53 or MDMX (MDM4)- p53 antagonist.
  • Known TP53 mutant tumor.
  • Symptomatic metastases from non-brain tumors; Note: Patients with previously treated brain metastases may participate provided they are stable, without evidence of progression by imaging (using the identical imaging modality for each assessment, either magnetic resonance imaging (MRI) or computed tomography (CT) scan), for at least four weeks prior to the first dose of trial treatment, and any neurologic symptoms have returned to baseline; have no evidence of new or enlarging brain metastases. Patients on corticosteroids must have a stable dose for at least 5 days prior to baseline MRI.
  • Patients with history of bleeding diathesis.
  • Major surgery (major according to the Investigator's assessment) performed within 12 weeks prior to start of study treatment, or planned within 12 months after screening (e.g. hip replacement).
  • Any other documented active or suspected malignancy or history of malignancy within 3 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix, or other local tumors considered cured by local treatment.
  • Patients who must or wish to continue the intake of restricted medications (see Section 4.2.2.1) or any drug considered likely to interfere with the safe conduct of the trial.
  • Currently enrolled in another investigational device or drug trial, or less than 30 days since receiving other investigational treatments. Patients who are in follow up/ observation for another clinical trial are eligible.
  • Known human immunodeficiency virus (HIV) infection, acute or chronic viral hepatitis. Patients with a history of hepatitis B virus infection, irrespective of their reactivation risk status, should also be excluded. The testing at screening is not mandatory and left at the discretion of investigator.
  • Known hypersensitivity to the trial drug or its excipients.
  • Serious concomitant disease or medical condition affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug, such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the Investigator, would make the patient inappropriate for entry into the trial.
  • Chronic alcohol or drug abuse or any condition that, in the Investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial.
  • Women who are pregnant, nursing, or who plan to become pregnant while in the trial; female patients who do not agree to the interruption of breast feeding from the start of study treatment until 6 months and 12 days after last dose of study treatment.

  • Any of the following cardiac criteria:

    • Mean resting corrected QT interval (QTcF) >470 msec
    • Any clinically important abnormalities (as assessed by the investigator) in rhythm, conduction, or morphology of resting electrocardiogram (ECGs), e.g., complete left bundle branch block, third degree heart block
    • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication known to prolong the QT interval
    • Ejection fraction (EF) <50% or the lower limit of normal of the institutional standard. Only in cases where the Investigator (or the treating physician or both) suspects cardiac disease with negative effect on the EF, will the EF be measured during screening using an appropriate method according to local standards to confirm eligibility (e.g., echocardiogram, multi-gated acquisition scan). A historic measurement of EF no older than 6 months prior to first administration of study drug can be accepted provided that there is clinical evidence that the patient's cardiac disease has not significantly worsened since this measurement in the opinion of the Investigator or of the treating physician or both.
    • Use of concomitant medications that are narrow therapeutic index drugs that are substrates of P-gp or BCRP (e.g. digoxin, dabigatran, etexilate).
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03449381


Contacts
Layout table for location contacts
Contact: Boehringer Ingelheim 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com

Locations
Layout table for location information
United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06511
Contact: Boehringer Ingelheim    833-602-2368    unitedstates@bitrialsupport.com   
United States, Florida
Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Contact: Boehringer Ingelheim    833-602-2368    unitedstates@bitrialsupport.com   
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Boehringer Ingelheim    833-602-2368    unitedstates@bitrialsupport.com   
United States, Tennessee
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
Contact: Boehringer Ingelheim    833-602-2368    unitedstates@bitrialsupport.com   
Belgium
UZ Leuven Recruiting
Leuven, Belgium, 3000
Contact: Boehringer Ingelheim    080049616    belgique@bitrialsupport.com   
Canada, Ontario
The Ottawa Hospital Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Boehringer Ingelheim    18336022346    canada@bitrialsupport.com   
Germany
Helios Klinikum Berlin-Buch Recruiting
Berlin, Germany, 13125
Contact: Boehringer Ingelheim    08007234742    deutschland@bitrialsupport.com   
Universitätsklinikum Köln (AöR) Recruiting
Köln, Germany, 50937
Contact: Boehringer Ingelheim    08007234742    deutschland@bitrialsupport.com   
Universitätsklinikum Tübingen Recruiting
Tübingen, Germany, 72076
Contact: Boehringer Ingelheim    08007234742    deutschland@bitrialsupport.com   
Japan
National Cancer Center Hospital Recruiting
Tokyo, Chuo-ku, Japan, 104-0045
Contact: Boehringer Ingelheim    0120201230    nippon@bitrialsupport.com   
Poland
MED POLONIA SP Z O O, Clinical Trials Department,Poznan Recruiting
Poznan, Poland, 60-693
Contact: Boehringer Ingelheim    008001218830    polska@bitrialsupport.com   
Oncology Center-Maria Sklodowska-Curie Institute Recruiting
Warsaw, Poland, 02-034
Contact: Boehringer Ingelheim    008001218830    polska@bitrialsupport.com   
Spain
Hospital Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Boehringer Ingelheim    900876092    espana@bitrialsupport.com   
Hospital Clínic de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Boehringer Ingelheim    900876092    espana@bitrialsupport.com   
Sponsors and Collaborators
Boehringer Ingelheim
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT03449381    
Other Study ID Numbers: 1403-0001
2017-003210-95 ( EudraCT Number )
First Posted: February 28, 2018    Key Record Dates
Last Update Posted: June 16, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description:

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

  1. studies in products where Boehringer Ingelheim is not the license holder;
  2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
  3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datasharing

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No