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

• ClinicalTrials.gov Identifier: NCT03449381
• Recruitment Status: Recruiting
• First Posted: February 28, 2018
• Last Update Posted: September 10, 2021
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Study Description

Brief Summary:

This study is open to adults with different types of advanced cancer (solid tumours).

The purpose of this study is to find out the highest dose of BI 907828 the participants can tolerate. In the second part, the study also tests whether BI 907828 makes tumours 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 one day in 2 consecutive weeks 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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 114 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 21, 2023
• Estimated Study Completion Date: June 13, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Phase Ia- Maximum tolreated 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

• 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 during or after all standard of care treatments. Patients who are not eligible to receive standard of care treatments, and for whom no proven treatments exist, are eligible.

• Phase Ia (dose escalation) only:

  --Patient has a tumor with either a known TP53 wild type 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 PK, PD, biomarker, and 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.
• Male or female ≥18 years old (for Japan, ≥20 years old) at the time of signature of the ICF
• 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, defined as female patients who are premenopausal or who had no cessation of menses within 12 months without an alternative medical cause, but not including female patients who are permanently sterilized) and men able to father a child must be ready and able to use two highly effective 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 35 days and 3 months, respectively for women and men, after trial completion (i.e. after the last administration of trial medication). 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.
• Patient has a tumor with a documented mutation in the TP53 gene determined previously or at screening irrespective of MDM2 amplification status. For dose escalation part only, patients who have tumors with unknown TP53 and/or MDM2 status at the time of screening are eligible at investigator's discretion.
• Active or untreated brain 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 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.
• Current use of warfarin, factor Xa inhibitors and direct thrombin inhibitors. Note: Low molecular weight heparin and prophylactic low dose warfarin are permitted; PT/PTT must meet the inclusion criteria; patients taking low dose warfarin must have their INR followed according to institutional guidelines.
• 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 followup/ observation for another clinical trial are eligible.
• Patients who have been treated with any other anticancer drug other than antibodies within 4 weeks or within 5 half-life periods (whichever come earlier) prior to first administration of BI 907828. For patients who have been previously treated with antibodies, within approximately 3 half-life periods prior to first administration of BI 907828.
• Persistent toxicity from previous treatments that has not resolved to ≤ CTCAE Grade 1 (except for alopecia and CTCAE Grade 2 neuropathy, or asthenia/fatigue).
• 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 to within 30 days after the last 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 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

Contacts

Contact: Boehringer Ingelheim; 1-800-243-0127; clintriage.rdg@boehringer-ingelheim.com

Locations

United States, Connecticut

Yale University School of Medicine; Recruiting

New Haven, Connecticut, United States, 06511

Contact: Patricia LoRusso +001 (203) 785-5944 Patricia.lorusso@yale.edu

United States, Florida

Florida Cancer Specialists; Recruiting

Sarasota, Florida, United States, 34232

Contact: Manish Patel +001 (941) 377-9993 MPatel@flcancer.com

United States, New York

Memorial Sloan-Kettering Cancer Center; Recruiting

New York, New York, United States, 10065

Contact: Mrinal Gounder +001 (646) 497-9067 gounderm@mskcc.org

United States, Tennessee

Tennessee Oncology, PLLC; Recruiting

Nashville, Tennessee, United States, 37203

Contact: Todd Bauer +001 (615) 329-7272 tbauer@tnonc.com

Belgium

UZ Leuven; Recruiting

Leuven, Belgium, 3000

Contact: Patrick Schöffski +32 (0)16 34 69 00 patrick.schoffski@uzleuven.be

Canada, Ontario

The Ottawa Hospital; Recruiting

Ottawa, Ontario, Canada, K1H 8L6

Contact: Scott Laurie 613-737-7700 x70175 slaurie@toh.on.ca

Japan

National Cancer Center Hospital; Recruiting

Tokyo, Chuo-ku, Japan, 104-0045

Contact: Noboru Yamamoto +81 3 35422511 nbryamam@ncc.go.jp

Sponsors and Collaborators

Boehringer Ingelheim

More Information

Additional Information:

Related Info 

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT03449381
• Other Study ID Numbers: 1403-0001; 2017-003210-95 ( EudraCT Number )
• First Posted: February 28, 2018
• Last Update Posted: September 10, 2021
• Last Verified: September 2021

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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No