Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    BI 1701963
Previous Study | Return to List | Next Study

A Study to Test Different Doses of BI 1701963 Alone and Combined With Trametinib in Patients With Different Types of Advanced Cancer (Solid Tumours With KRAS Mutation)

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: NCT04111458
Recruitment Status : Recruiting
First Posted : October 1, 2019
Last Update Posted : November 13, 2019
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:

The primary objective of this trial is to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of BI 1701963 as monotherapy and in combination with trametinib in patients with KRAS mutated solid tumours.

Secondary objectives are to evaluate the safety and tolerability of BI 1701963 as monotherapy and in combination with trametinib, to characterise pharmacokinetics and pharmacodynamics, and to evaluate first efficacy signals.


Condition or disease Intervention/treatment Phase
Solid Tumors, KRAS Mutation Drug: BI 1701963 Drug: Trametinib Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Open-label Dose Escalation Trial of BI 1701963 as Monotherapy and in Combination With Trametinib in Patients With KRAS Mutated Advanced or Metastatic Solid Tumours
Actual Study Start Date : October 28, 2019
Estimated Primary Completion Date : November 18, 2020
Estimated Study Completion Date : November 15, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Trametinib

Arm Intervention/treatment
Experimental: BI 1701963 monotherapy Drug: BI 1701963
Tablet

Experimental: BI 1701963 + Trametinib Drug: BI 1701963
Tablet

Drug: Trametinib
Tablet




Primary Outcome Measures :
  1. Dose escalation (Part A) - Maximum tolerated dose (MTD) based on number of dose-limiting toxicities (DLTs) [ Time Frame: 4 weeks ]
  2. Dose confirmation (Part B) - Number of patients with DLTs during the on-treatment period [ Time Frame: Up to 3 years ]
  3. Dose confirmation (Part B) and expansion (Part C) - Objective response [ Time Frame: Up to 3 years ]

Secondary Outcome Measures :
  1. Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of BI 1701963: Cmax (maximum measured concentration of the analyte in plasma) [ Time Frame: Up to 5 weeks ]
  2. Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of BI 1701963: AUCτ (area under the concentration-time curve over a uniform dosing interval τ) [ Time Frame: Up to 5 weeks ]
  3. Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of trametinib: Cmax (maximum measured concentration of the analyte in plasma) [ Time Frame: Up to 5 weeks ]
  4. Dose escalation (Part A), confirmation (Part B) and expansion (Part C) - Pharmacokinetic parameters of trametinib: AUCτ (area under the concentration-time curve over a uniform dosing interval τ) [ Time Frame: Up to 5 weeks ]
  5. Dose confirmation (Part B) - Pharmacokinetic parameters of BI 1701963: Cmax (maximum measured concentration of the analyte in plasma) [ Time Frame: Up to 5 weeks ]
  6. Dose confirmation (Part B) - Pharmacokinetic parameters of BI 1701963: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) [ Time Frame: Up to 5 weeks ]
  7. Dose confirmation (Part B) - Pharmacokinetic parameters of midazolam: Cmax (maximum measured concentration of the analyte in plasma) [ Time Frame: Up to 5 weeks ]
  8. Dose confirmation (Part B) - Pharmacokinetic parameters of midazolam: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) [ Time Frame: Up to 5 weeks ]
  9. Dose confirmation (Part B) - Number of patients with Grade ≥3 treatment-related adverse events observed during the on-treatment period [ Time Frame: Up to 3 years ]
  10. Dose confirmation (Part B) and expansion (Part C) - Duration of Objective response (OR) [ Time Frame: Up to 3 years ]
  11. Dose confirmation (Part B) and expansion (Part C) - Tumour shrinkage (in millimetres) [ Time Frame: Up to 3 years ]
  12. Dose confirmation (Part B) and expansion (Part C) - Progression-free survival [ Time Frame: 6 months ]
  13. Dose confirmation (Part B) and expansion (Part C) - Number of patients with Grade ≥3 treatment-related adverse events observed during the on-treatment period [ Time Frame: Up to 3 years ]


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:

All parts

  • Previously-identified activating Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation in tumour tissue
  • At least one target lesion that can be measured per Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate organ function
  • Age ≥18 years of age, or over the legal age of consent as required by local legislation.
  • Signed and dated written informed consent in accordance with GCP and local legislation prior to admission to the trial.
  • Women of childbearing potential who are not surgically sterilized must have a negative serum pregnancy test completed during the Screening period
  • Further inclusion criteria apply

Monotherapy and combination therapy dose escalation and monotherapy dose confirmation part

- Documented disease progression despite appropriate prior standard therapies or for whom no standard therapy exists for their tumour type and disease stage

Combination dose confirmation and expansion cohort

  • Pathologically confirmed diagnosis of adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology.
  • Locally advanced stage IIIb or metastatic stage IV Non-small cell lung cancer (NSCLC)
  • Patients must have received both chemotherapy and immunotherapy

Exclusion criteria:

All parts

  • Previous anticancer chemotherapy within 3 weeks of the first administration of trial drug.
  • Previous treatment with RAS, Mitogen-activated protein kinase (MAPK) or Son of sevenless 1 (SOS1) targeting agents
  • Major surgery performed within 4 weeks prior to start of treatment
  • Uncontrolled hypertension, congestive heart failure NYHA classification of ≥3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to start of treatment
  • Left ventricular ejection fraction (LVEF) <50 %
  • Congenital long QT prolongation syndrome
  • Mean resting corrected QT interval (QTcF) >470 msec
  • Leptomeningeal carcinomatosis
  • Presence or history of uncontrolled or symptomatic brain metastases
  • Known pre-existing interstitial lung disease
  • Known active hepatitis B infection (defined as presence of Hep B sAg and/or Hep B Deoxyribonucleic acid (DNA)), active hepatitis C infection (defined as presence of Hep C Ribonucleic acid (RNA))
  • Active infectious disease
  • Any history or presence of uncontrolled gastrointestinal disorders that could affect the intake and/or absorption of the trial drug
  • History of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED)
  • Further exclusion criteria apply

Combination part

- Hypersensitivity to any of the excipients listed in the current Summary of Product Characteristics (SmPC)/Package insert (PI) of trametinib


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): NCT04111458


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

Locations
Layout table for location information
Netherlands
Universitair Medisch Centrum Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Contact: Eelke Gort    +31(0)887556308    E.H.Gort-2@umcutrecht.nl   
Sponsors and Collaborators
Boehringer Ingelheim

Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT04111458     History of Changes
Other Study ID Numbers: 1432-0001
2018-004757-24 ( EudraCT Number )
First Posted: October 1, 2019    Key Record Dates
Last Update Posted: November 13, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https:// trials.boehringer‐ingelheim.com/trial_results/ clinical_submission_documents.html to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link http://trials.boehringer-ingelheim.com/ to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor'
URL: https://trials.boehringer‐ingelheim.com

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Trametinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action