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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 : March 18, 2020
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE September 27, 2019
First Posted Date  ICMJE October 1, 2019
Last Update Posted Date March 18, 2020
Actual Study Start Date  ICMJE October 28, 2019
Estimated Primary Completion Date November 18, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 30, 2019)
  • Dose escalation (Part A) - Maximum tolerated dose (MTD) based on number of dose-limiting toxicities (DLTs) [ Time Frame: 4 weeks ]
  • Dose confirmation (Part B) - Number of patients with DLTs during the on-treatment period [ Time Frame: Up to 3 years ]
  • Dose confirmation (Part B) and expansion (Part C) - Objective response [ Time Frame: Up to 3 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 30, 2019)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Dose confirmation (Part B) - Pharmacokinetic parameters of BI 1701963: Cmax (maximum measured concentration of the analyte in plasma) [ Time Frame: Up to 5 weeks ]
  • 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 ]
  • Dose confirmation (Part B) - Pharmacokinetic parameters of midazolam: Cmax (maximum measured concentration of the analyte in plasma) [ Time Frame: Up to 5 weeks ]
  • 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 ]
  • 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 ]
  • Dose confirmation (Part B) and expansion (Part C) - Duration of Objective response (OR) [ Time Frame: Up to 3 years ]
  • Dose confirmation (Part B) and expansion (Part C) - Tumour shrinkage (in millimetres) [ Time Frame: Up to 3 years ]
  • Dose confirmation (Part B) and expansion (Part C) - Progression-free survival [ Time Frame: 6 months ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumors, KRAS Mutation
Intervention  ICMJE
  • Drug: BI 1701963
    Tablet
  • Drug: Trametinib
    Tablet
Study Arms  ICMJE
  • Experimental: BI 1701963 monotherapy
    Intervention: Drug: BI 1701963
  • Experimental: BI 1701963 + Trametinib
    Interventions:
    • Drug: BI 1701963
    • Drug: Trametinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 30, 2019)
140
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 15, 2022
Estimated Primary Completion Date November 18, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Boehringer Ingelheim 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com
Listed Location Countries  ICMJE Netherlands,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04111458
Other Study ID Numbers  ICMJE 1432-0001
2018-004757-24 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: 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
Responsible Party Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Boehringer Ingelheim
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP