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EUCTR2016-003498-16
Alternative entry with additional local information: NCT02637687

A Phase 1/2 Clinical Trial of Pediatric Cancer Patients With Solid Tumors Treated with Larotrectinib

Data source: WHO (Imported from 22.11.2020)
Changed: 22.11.2020
Disease category:

Health conditions (Data source: WHO)

Central Nervous System Neoplasms and advanced solid tumors
MedDRA version: 21.0Level: LLTClassification code 10049516Term: Malignant tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0Level: LLTClassification code 10007959Term: Central nervous system neoplasm NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0Level: PTClassification code 10007958Term: Central nervous system neoplasmSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 20.1Level: HLTClassification code 10007960Term: Central nervous system neoplasms malignant NECSystem Organ Class: 100000004852;Therapeutic area: Diseases [C] - Cancer [C04]

Interventions (Data source: WHO)


Product Name: larotrectinib
Product Code: BAY 2757556
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: larotrectinib
Other descriptive name: BAY 2757556
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Product Name: larotrectinib
Product Code: BAY 2757556
Pharmaceutical Form: Oral solution
INN or Proposed INN: larotrectinib
Other descriptive name: BAY 2757556
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Product Name: larotrectinib
Product Code: BAY 2757556
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: larotrectinib
Other descriptive name: BAY 2757556
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: larotrectinib
Product Code: BAY 2757556
Pharmaceutical Form: Oral solution
INN or Proposed INN: larotrectinib
Other descriptive name: BAY 2757556
Concentration unit: % percent
Concentration type: equal
Concentration number: 2-

Inclusion/Exclusion Criteria (Data source: WHO)

Inclusion criteria:
Starting from Protocol Version 11 (10 JUL 2019), newly enrolled patients will only enter Phase 2.
1.Phase 1: Birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies for whIch no standard or available systemic curative therapy exists or
Infants from birth and older with a diagnosis of malignancy and with a documented NTRK fusion that hAs progressed or was nonresponsive to available therapies for which no standard or systemic curative therapy exists or
Phase 2: Patients with locally advanced or metastatic infantile fibrosarcoma who would require in the opinion of the Investigator disfiguring surgery or limb amputation to achieve a complete surgical resection with documented ETV6 rearrangement (or NTRK3 rearrangement after discussion with the Sponsor) by FISH or RT-PCR or a documented NTRK fusion by e.g. NGS. or:
Birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies for whIch no standard or available systemic curative therapy exists, with a documented NTRK gene fusion e.g. by NGS or in case of IFS, CMN or SBC with documented ETV6 rearrangement (or NTRK3 rearangement after discussion with the sponsor) by FISH or RT-PCR. Documented NTRK fusion by NGS shall identified through molecular assays as routinely performed at CLIA or other similarly-certified laboratories. If CLIA or similar certification of the laboratory performing the molecular assay is not confirmed at the time of consent patients may be included after discussion with
the Sponsor. Patients with NTRK fusion positive benign tumors are also eligible.
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
Willingness of male and female patients with reproductive potential to utilize double effective birth control methods for the duration of treatment and for 1 month following study completion
Ability to swallow capsules, liquid or gastric access via a naso- or gastric tube
Are the trial subjects under 18? yes
Number of subjects for this age range: 161
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 13
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients meeting any of the following criteria are to be excluded from study participation:
1. Major surgery within 14 days (2 weeks) prior to C1D1.
2. Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to C1D1; ongoing cardiomyopathy; or current prolonged QTc interval > 480 milliseconds.
3. Active uncontrolled systemic bacterial, viral, or fungal infection.
4. Malabsorption syndrome or other condition affecting oral absorption.
5. Current treatment with a strong CYP3A4 inhibitor or inducer other than those allowed per Section 6.3.2 of the study protocol.
6. Pregnancy or lactation.
7. Phase 2 only: Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting TRK, including entrectinib, crizotinib and lestaurtanib. Patients who received a TRK inhibitor for less than 28 days of treatment and discontinued because of intolerance remain eligible.

Further information on the trial in WHO primary registry

https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003498-16

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2016-003498-16-NL

Further information on trial

Date trial registered

23.01.2018

Incorporation of the first participant

25.09.2018

Recruitment status

Authorised-recruitment may be ongoing or finished

Academic title (Data source: WHO)

A Phase 1/2 Study of the Oral TRK Inhibitor Larotrectinib in Pediatric Patients with Advanced Solid or Primary Central Nervous System Tumors - SCOUT

Type of trial (Data source: WHO)

Interventional clinical trial of medicinal product

Design of the trial (Data source: WHO)

Controlled: noRandomised: noOpen: yesSingle blind: noDouble blind: noParallel group: noCross over: noOther: noIf controlled, specify comparator, Other Medicinial Product: noPlacebo: noOther: no

Phase (Data source: WHO)

Human pharmacology (Phase I): yesTherapeutic exploratory (Phase II): yesTherapeutic confirmatory - (Phase III): noTherapeutic use (Phase IV): no

Primary end point (Data source: WHO)

Timepoint(s) of evaluation of this end point: Every cohort from baseline until disease progression,unacceptable toxicity, patient’s withdrawal of consent, or death.
;Main Objective: Starting from Protocol V.11 (10JUL2019), newly enrolled patients will only enter Phase II.
Phase I: Determine safety of oral larotrectinib, including Dose-Limiting Toxicity (DLT), in pediatric patients with advanced solid or primary CNS tumors.
Phase II: To determine the overall response rate (ORR) as determined by an independent radiology review committee and measured by the proportion of patients with best overall confirmed response of complete response (CR) or partial response (PR) according to the appropriate tumor response criteria following treatment with larotrectinib in pediatric patients with an advanced cancer harboring a fusion involving NTRK1, NTRK2, or NTRK3 (referred to as NTRK fusions).
;Secondary Objective: To determine the ORR based on the treating investigator's response assessment using RANO for primary CNS tumor criteria, and INRC for neuroblastoma and RECIST 1.1 for all other solid tumors.
To evaluate the duration of response in patients with best overall response of CR or PR as determined by 1) an independant radilogy review committee and 2) the treating investigator
To estimate the proportion of patients that are in tumor regression as a best response
To evaluate the duration of PFS following initiation of larotrectinib
To evaluate the duration of OS following initiation of larotrectinib
;Primary end point(s): Phase I: Safety of oral larotrectinib, including dose-limiting toxicity (DLT) until the Maximum Tolerated Dose or suitable dose based on PK exposure or unacceptable DLT are reached.
Phase II: Overall response rate (ORR) as determined by an independent radiology review committee and measured by the proportion of subjects with best overall confirmed response of complete response (CR) or partial response (PR) by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), or Response Assessment in Neuro-Oncology (RANO) criteria for primary CNS tumors, and International Neuroblastoma Response Criteria (INRC) for neuroblastoma, as appropriate.

Secundary end point (Data source: WHO)

Secondary end point(s): PK analysis: Plasm and CSF concentrations of larotrectinib will be determined with a validtaed bioanalytical assay.
Pain and Health related QoL: in patients 3 years age or older pain will be assessed by the Wong-Baker Faces scale. ;Timepoint(s) of evaluation of this end point: The PK parameters will be calculated from the C1D1 and C2D1 (cohorts 1&2)and C4D1 (Phase 1 Dose Escalation cohort 3, Phase 1 Dose Expansion cohorts and Phase 2 Efficacy cohorts).
Pain and Health related QoL: Mean changes over time will be analyzed descriptively by time-point.

Contact information (Data source: WHO)

Bayer Consumer Care AG

Trial results (Data source: WHO)

Results summary

A Phase 1/2 Study of the Oral TRK Inhibitor Larotrectinib in Pediatric Patients with Advanced Solid or Primary Central Nervous System Tumors

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Countries (Data source: WHO)

Australia, Canada, China, Denmark, France, Germany, Ireland, Israel, Italy, Japan, Korea, Netherlands, Poland, Republic of, Spain, Sweden, Switzerland, United Kingdom, United States

Contact for further information on the trial

Contact for general information (Data source: WHO)

Bayer Clinical Trials Contact
Bayer AG
clinical-trials-contact@bayer.com

Contact for scientific information (Data source: WHO)

Bayer Clinical Trials Contact
Bayer AG
clinical-trials-contact@bayer.com

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

Bayer Consumer Care AG

Further trial identification numbers

Secondary ID (Data source: WHO)

20290
NCT02637687
BAY 2757556 / 20290
2016-003498-16-ES