Solid Tumors Harboring NTRK FusionPhase 1NCT03215511
A Study to Test the Safety of the Investigational Drug Selitrectinib in Children and Adults That May Treat Cancer
A Phase 1 study testing Selitrectinib (BAY2731954) in people with Solid Tumors Harboring NTRK Fusion, run by Bayer at 29 sites in 10 countries.
Trial summary
This research study is done to test the safety of the new drug selitrectinib in children and adults with cancer having a change in a particular gene (NTRK1, NTRK2 or NTRK3). The drug may treat cancer by interfering with the effect of the NTRK genes on cancer growth. Read more about this study
- Who is it for?
- Ages 1 month and older
- Conditions the study is for
- Solid Tumors Harboring NTRK Fusion
- What is being tested?
- Selitrectinib (BAY2731954)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 29 sitesin 10 countries
- Study dates
- 3 Jul 2017to 30 Jan 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Advanced solid tumor for which, in the opinion of the investigator, no other standard therapy offers greater benefit.
- A solid tumor diagnosis in the setting of:
- a) a documented NTRK fusion and a clinical history of relapse following a response to a prior TRK inhibitor
- b) a documented NTRK fusion unresponsive to a prior TRK inhibitor
- c) a documented NTRK fusion and a clinical history of intolerance to a prior TRK inhibitor
- NTRK gene fusions will be identified in a CLIA-certified (or equivalently-accredited diagnostic) laboratory. If such a report cannot be provided, other available certifications/accreditations are required and need to be documented. Patients with infantile fibrosarcoma (IFS) or congenital mesoblastic nephroma (CMN) may be enrolled based on an ETV6+ FISH test without identifying NTRK3.
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- Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 2 in adults or Karnofsky Performance Status (KPS) Score≥50% (age ≥ 16 years) or Lansky Performance Score (LPS) ≥ 40% (age < 16 years).
- Life expectancy of at least 3 months.
- Adequate hematologic, hepatic and renal function.
- Patients with stable central nervous system (CNS) primary tumor, brain metastases, or treated spinal cord compression are eligible if neurological symptoms have been stable for 7 days prior to the first dose of selitrectinib.
- Ability to receive study drug orally or by enteral administration
Who cannot join
- Prior exposure to second generation TRK inhibitor (e.g. selitrectinib, repotrectinib [TPX-0005]), taletrectinib [DS-6501b/AB-106]). Exception is in case patient presented intolerance to the second generation TRK inhibitor agent and the duration of exposure was less than 28 days. No previous treatment with selitrectinib is allowed.
- Concurrent treatment with a strong CYP3A4 inhibitor or inducer, consumption of grapefruit juice or Seville oranges, or drugs associated with QT prolongation.
- Clinically significant active cardiovascular disease or history of myocardial infarction within 3 months prior to planned start of selitrectinib, or prolongation of QT interval corrected for heart rate (QTc interval) >480 milliseconds within past 6 months
- Major surgery within 7 days of enrollment
- Uncontrolled systemic bacterial, fungal or viral infection.
- Pregnancy or lactation.
- Known hypersensitivity to selitrectinib or Ora-Sweet® SF and OraPlus® for patients receiving liquid formulation.
Trial locations and contacts
29 sites in 10 countries.
29 sites in 10 countries
United States17 sites
University of Michigan
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Massachusetts General Hospital
Boston, Massachusetts, 02114-2696
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Univ.of California-San Diego Moores Cancer Center
La Jolla, California, 92093
UCLA Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095-1781
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Virginia Oncology Associates
Norfolk, Virginia, 23502
Stanford Cancer Center
Palo Alto, California, 94304
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Oregon Health and Science University
Portland, Oregon, 97239
Seattle Children's Hospital
Seattle, Washington, 98105
Avera Cancer Institute
Sioux Falls, South Dakota, 57105
Midwestern Regional Medical Center
Zion, Illinois, 60099
Australia2 sites
Royal Children's Hospital Melbourne
Parkville, Victoria, 3052
Sydney Children's Hospital
Sydney, New South Wales, 2031
France2 sites
Institut Curie - Ulm - Paris
Paris, 75248
Institut Gustave Roussy - Département de Médecine Oncologique
Villejuif, 94805
Spain2 sites
Ciutat Sanitaria i Universitaria de la Vall d'Hebron
Barcelona, 08035
Fundacion Jimenez Diaz (Clinica de la Concepcion)
Madrid, 28040
Germany1 site
Universitätsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69115
Italy1 site
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Lombardy, 20133
About this study
Official title: A Phase 1 Study of the TRK Inhibitor Selitrectinib (BAY 2731954) in Adult and Pediatric Subjects With Previously Treated NTRK Fusion Cancers
This research study is done to test the safety of the new drug selitrectinib in children and adults with cancer having a change in a particular gene (NTRK1, NTRK2 or NTRK3). The drug may treat cancer by interfering with the effect of the NTRK genes on cancer growth. The study also investigates how the drug is absorbed and processed in the human body, and how well and for how long the cancer responds to the drug. This is the first study to test selitrectinib in humans with cancer, for whom no other effective therapy exists.
Read the detailed description
The primary objective is to determine the recommended dose for further study of oral selitrectinib with previously treated neurotrophic tyrosine kinase (NTRK) cancers in 2 patient groups: a) aged 12 years and older and b) younger than 12 years. Secondary objectives of Phase I are to characterize the pharmakokinetic properties of the test drug, its safety and tolerability, and to assess the objective response rate (ORR) of NTRK-tumors.
- Conditions
- Solid Tumors Harboring NTRK Fusion
- Being tested
- Selitrectinib (BAY2731954)
- Keywords
- Solid Tumor, Metastatic cancer, Advanced cancer, Neurotrophic tyrosine receptor kinase (NTRK), NTRK1, NTRK2, NTRK3, Fusion Positive, Children
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Selitrectinib (BAY2731954)Drug
Also called Loxo-195
Selitrectinib is administered as capsules or liquid formulation.
| Study group | Role | What they receive |
|---|---|---|
| Cancer participants <12 years | Experimental | A Rolling-6 dose escalation design will be used. The starting dose for participants age < 12 years will be 25% below the highest dose level cohort divided by 1.73 m^2 cleared by the Safety Review Committee (SRC) for subjects age 12 years and older. Receives: Drug: Selitrectinib (BAY2731954) |
| Cancer participants ≥12 years | Experimental | A 3+3 dose escalation design will be used to determine the maximum tolerated dose (MTD)/recommended dose for further study, enrolling 3 to 6 participants per cohort with a starting dose level of 100 mg twice daily (BID). Receives: Drug: Selitrectinib (BAY2731954) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
Measured: Up to 42 days
Recommended dose
Measured: Up to 12 months
Secondary outcomes (9)
Incidence of adverse events
Measured: Up to 56 months
Severity of adverse events
Severity is assessed using CTCAE version 4.03
Measured: Up to 56 months
Duration of adverse events
Measured: Up to 56 months
Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration
Measured: Up to 56 months
Severity of safety-relevant changes in clinical parameters or vital signs after drug administration
Measured: Up to 56 months
Overall response rate (ORR) in subjects with NTRK fusion cancer previously treated with TRK inhibitor determined by investigator
ORR is determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measured: Up to 56 months
Overall response rate (ORR) in subjects with primary central nervous system (CNS) malignancies determined by investigator
ORR is determined by the treating investigator using the Response Assessment in Neuro-Oncology (RANO) criteria.
Measured: Up to 56 months
Maximum concentration (Cmax) of BAY2731954 in plasma
Measured: Predose, 0.25, 0.5, 1, 2, 4, 6, 8 hours post-dose on Day 1, predose, 0.5, 1, 2, 4 post-dose on Day 8 of Cycle 1 (cycle length 28 days)
Area under the concentration versus time curve of BAY2731954 in plasma (AUC (0-10), AUC(0-12) for BID dosing and AUC(0-24) for QD dosing)
Measured: At defined time points for different cohort, up to 10 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2017
- Study start3 Jul 2017
- Primary completion11 Apr 2022
- Study completion30 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid Tumors Harboring NTRK FusionStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03215511
- Sponsor's protocol ID
- 20810
- Other IDs
- LOXO-EXT-17005, 2017-004246-20, 2017
- Status last verified
- Oct 2024
- First submitted
- 30 Jun 2017
- Last updated
- 30 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.
- Expanded access
- Available
Publications
O'Reilly EM, Hechtman JF. Tumour response to TRK inhibition in a patient with pancreatic adenocarcinoma harbouring an NTRK gene fusion. Ann Oncol. 2019 Nov 1;30(Suppl_8):viii36-viii40. doi: 10.1093/annonc/mdz385. Epub 2019 Dec 24.
PubMed 31605106
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of the TRK Inhibitor Selitrectinib (BAY 2731954) in Adult and Pediatric Subjects With Previously Treated NTRK Fusion Cancers
- ClinicalTrials.gov ID
- NCT03215511
- Acronym / sponsor ID
- 20810
- Conditions
- Solid Tumors Harboring NTRK Fusion
- Keywords
- Solid Tumor, Metastatic cancer, Advanced cancer, Neurotrophic tyrosine receptor kinase (NTRK), NTRK1, NTRK2, NTRK3, Fusion Positive
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 3 Jul 2017 (actual)
- Primary completion
- 11 Apr 2022 (actual)
- Study completion
- 30 Jan 2023 (actual)
- First posted
- 12 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is done to test the safety of the new drug selitrectinib in children and adults with cancer having a change in a particular gene (NTRK1, NTRK2 or NTRK3). The drug may treat cancer by interfering with the effect of the NTRK genes on cancer growth. The study also investigates how the drug is absorbed and processed in the human body, and how well and for how long the cancer responds to the drug. This is the first study to test selitrectinib in humans with cancer, for whom no other effective therapy exists.
Detailed description
The primary objective is to determine the recommended dose for further study of oral selitrectinib with previously treated neurotrophic tyrosine kinase (NTRK) cancers in 2 patient groups: a) aged 12 years and older and b) younger than 12 years. Secondary objectives of Phase I are to characterize the pharmakokinetic properties of the test drug, its safety and tolerability, and to assess the objective response rate (ORR) of NTRK-tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cancer participants <12 years | Experimental | Drug: Selitrectinib (BAY2731954)A Rolling-6 dose escalation design will be used. The starting dose for participants age < 12 years will be 25% below the highest dose level cohort divided by 1.73 m^2 cleared by the Safety Review Committee (SRC) for subjects age 12 years and older. |
| Cancer participants ≥12 years | Experimental | Drug: Selitrectinib (BAY2731954)A 3+3 dose escalation design will be used to determine the maximum tolerated dose (MTD)/recommended dose for further study, enrolling 3 to 6 participants per cohort with a starting dose level of 100 mg twice daily (BID). |
Who may qualify
- Ages
- 1 month and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Advanced solid tumor for which, in the opinion of the investigator, no other standard therapy offers greater benefit.
- A solid tumor diagnosis in the setting of:
- NTRK gene fusions will be identified in a CLIA-certified (or equivalently-accredited diagnostic) laboratory. If such a report cannot be provided, other available certifications/accreditations are required and need to be documented. Patients with infantile fibrosarcoma (IFS) or congenital mesoblastic nephroma (CMN) may be enrolled based on an ETV6+ FISH test without identifying NTRK3.
- Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 2 in adults or Karnofsky Performance Status (KPS) Score≥50% (age ≥ 16 years) or Lansky Performance Score (LPS) ≥ 40% (age < 16 years).
- Life expectancy of at least 3 months.
Key exclusion criteria (7 listed)
- Prior exposure to second generation TRK inhibitor (e.g. selitrectinib, repotrectinib [TPX-0005]), taletrectinib [DS-6501b/AB-106]). Exception is in case patient presented intolerance to the second generation TRK inhibitor agent and the duration of exposure was less than 28 days. No previous treatment with selitrectinib is allowed.
- Concurrent treatment with a strong CYP3A4 inhibitor or inducer, consumption of grapefruit juice or Seville oranges, or drugs associated with QT prolongation.
- Clinically significant active cardiovascular disease or history of myocardial infarction within 3 months prior to planned start of selitrectinib, or prolongation of QT interval corrected for heart rate (QTc interval) >480 milliseconds within past 6 months
- Major surgery within 7 days of enrollment
- Uncontrolled systemic bacterial, fungal or viral infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Selitrectinib (BAY2731954)Also: Loxo-195Selitrectinib is administered as capsules or liquid formulation. | Drug | Cancer participants <12 years, Cancer participants ≥12 years |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: Up to 42 days
Recommended dose
Time frame: Up to 12 months
9 secondary outcomes
Incidence of adverse events
Time frame: Up to 56 months
Severity of adverse events
Time frame: Up to 56 months
Duration of adverse events
Time frame: Up to 56 months
Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration
Time frame: Up to 56 months
Severity of safety-relevant changes in clinical parameters or vital signs after drug administration
Time frame: Up to 56 months
Overall response rate (ORR) in subjects with NTRK fusion cancer previously treated with TRK inhibitor determined by investigator
Time frame: Up to 56 months
Overall response rate (ORR) in subjects with primary central nervous system (CNS) malignancies determined by investigator
Time frame: Up to 56 months
Maximum concentration (Cmax) of BAY2731954 in plasma
Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8 hours post-dose on Day 1, predose, 0.5, 1, 2, 4 post-dose on Day 8 of Cycle 1 (cycle length 28 days)
Area under the concentration versus time curve of BAY2731954 in plasma (AUC (0-10), AUC(0-12) for BID dosing and AUC(0-24) for QD dosing)
Time frame: At defined time points for different cohort, up to 10 hours post-dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2024.
- Derived from this study: PubMed 31605106O'Reilly EM, Hechtman JF. Tumour response to TRK inhibition in a patient with pancreatic adenocarcinoma harbouring an NTRK gene fusion. Ann Oncol. 2019 Nov 1;30(Suppl_8):viii36-viii40. doi: 10.1093/annonc/mdz385. Epub 2019 Dec 24.
- Click here to find information about studies related to Bayer Healthcare products conducted in Europe.Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
29 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Selitrectinib (BAY2731954) in people with Solid Tumors Harboring NTRK Fusion, run by Bayer at 29 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Australia, France, Spain, Belgium and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) (time frame: Up to 42 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03215511, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2024.