do_not_disturb_altRecruitment Complete
Solid tumors harboring NTRK fusion
Bayer Identifier:
20290
ClinicalTrials.gov Identifier:
EudraCT Number:
EU CT Number:
Not Available
A study to test the safety and efficacy of the drug larotrectinib for the treatment of tumors with NTRK-fusion in children
Trial purpose
The study is being done to test the safety of a cancer drug called larotrectinib in children. The cancer must have a change in a particular gene (NTRK1, NTRK2 or NTRK3). Larotrectinib blocks the actions of these NTRK genes in cancer cells and can therefore be used to treat cancer.
The first study part (Phase 1) is done to determine what dose level of larotrectinib is safe for children, how the drug is absorbed and changed by their bodies and how well the cancer responds to the drug. The main purpose of the second study part (Phase 2) is to investigate how well and how long different cancer types respond to the treatment with larotrectininb.
The first study part (Phase 1) is done to determine what dose level of larotrectinib is safe for children, how the drug is absorbed and changed by their bodies and how well the cancer responds to the drug. The main purpose of the second study part (Phase 2) is to investigate how well and how long different cancer types respond to the treatment with larotrectininb.
Key Participants Requirements
Sex
AllAge
NaN - 21 YearsTrial summary
Enrollment Goal
154Trial Dates
December 2015 - September 2026Phase
Phase 1/Phase 2Could I Receive a placebo
NoProducts
Vitrakvi (Larotrectinib, BAY2757556)Accepts Healthy Volunteer
NoWhere to participate
Status | Institution | Location |
---|---|---|
Active, not recruiting | Institut Curie - Ulm - Paris | PARIS cedex 5, 75248, France |
Active, not recruiting | Gustave Roussy - Departement Oncologie-Radiotherapie | VILLEJUIF CEDEX, 94805, France |
Completed | Uniwersyteckie Centrum Kliniczne | Gdansk, 80-214, Poland |
Active, not recruiting | Karolinska Universitetssjukhuset i Solna | Stockholm, 171 76, Sweden |
Active, not recruiting | Clalit Health Services Schneider Children's Medical Center | Petach Tikva, 4920235, Israel |
Active, not recruiting | Sydney Children’s Hospital | Sydney, 2031, Australia |
Completed | Royal Children's Hospital Melbourne | Parkville, 3052, Australia |
Active, not recruiting | Universitätskinderspital Zürich | Zürich, 8032, Switzerland |
Active, not recruiting | Rigshospitalet - Børn og Unge | Copenhagen, 2100, Denmark |
Completed | Nemours Children’s Hospital (Orlando) | Orlando, 32827, United States |
Active, not recruiting | Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Pediatria Oncologica | Milano, 20133, Italy |
Withdrawn | A.O.U. di Padova | Padova, 35128, Italy |
Active, not recruiting | Royal Marsden NHS Trust (Surrey) | Sutton, SM2 5PT, United Kingdom |
Active, not recruiting | Children's Health Ireland Crumlin | Crumlin, 12, Ireland |
Active, not recruiting | University of Texas Southwestern Medical Center | Dallas, 75390, United States |
Active, not recruiting | Children's Hospital Los Angeles - Hematology/Oncology | Los Angeles, 90027, United States |
Active, not recruiting | Dana-Farber Cancer Institute | Boston, 02215, United States |
Active, not recruiting | Memorial Sloan Kettering Cancer Center | New York, 10021-0005, United States |
Active, not recruiting | St. Jude Children's Research Hospital | Memphis, 38105, United States |
Active, not recruiting | Seattle Children's Hospital | Seattle, 98105, United States |
Completed | Cincinnati Children's Hospital Medical Center | Division of Nephrology and Hypertension | Cincinnati, 45229, United States |
Active, not recruiting | UCLA Jonsson Comprehensive Cancer Center | Los Angeles, 90095-1781, United States |
Completed | Lucille Packard Children's Hospital Stanford - Pediatric Nephrology | Palo Alto, 94304, United States |
Active, not recruiting | Tianjin Medical University Cancer Institute & Hospital | Tianjin, 300000, China |
Active, not recruiting | Beijing Children's Hospital, Capital Medical University | Beijing, 100045, China |
Withdrawn | Tohoku University Hospital | Sendai, 980-8574, Japan |
Active, not recruiting | National Cancer Center Hospital | Chuo-ku, 104-0045, Japan |
Active, not recruiting | Sun Yat-sen University Cancer Center | Guangzhou, 510000, China |
Active, not recruiting | The Hospital for Sick Children (SickKids) | Toronto, M5G 1X8, Canada |
Active, not recruiting | CHU Sainte-Justine | Montreal, H3T 1C5, Canada |
Active, not recruiting | Charité - Campus Virchow-Klinikum (CVK), Klinik für Pädiatrie mit Schwerpunkt Onkologie und Hämatologie | Berlin, 13353, Germany |
Active, not recruiting | KLINIKUM STUTTGART - Olgahospital | Paediatrie 5 (Onkologie, Haematologie, Immunologie) | Stuttgart, 70174, Germany |
Active, not recruiting | Universitaetsklinikum Heidelberg - KiTZ | Klinik für Paediatrische Onkologie, Haematologie, Immunologie und Pneumologie | Heidelberg, 69120, Germany |
Active, not recruiting | Ciutat Sanitaria i Universitaria de la Vall d'Hebron | Barcelona, 08035, Spain |
Active, not recruiting | Prinses Maxima Centrum | UTRECHT, 3584 CS, Netherlands |
Completed | Seoul National University Hospital | Seoul, 3080, Korea,_republic_of |
Active, not recruiting | Severance Hospital, Yonsei University Health System | Seoul, 03722, Korea,_republic_of |
Active, not recruiting | Kanagawa Children's Medical Center | Yokohama, 252-8555, Japan |
Withdrawn | Local Incorporated Administrative Agency Osaka City Hospital Organization Osaka City General Hospital | Osaka, 534-0021, Japan |
Completed | Kyushu University Hospital | Fukuoka, 812-8582, Japan |
Active, not recruiting | BC Children's Hospital - Hematology/Oncology | Vancouver, V6H 3N1, Canada |
Active, not recruiting | Children's Hospital of Philadelphia - Hematology/Oncology | Philadelphia, 19104, United States |
Withdrawn | Alberta Childrens Hospital | Calgary, T3B 6A8, Canada |
Active, not recruiting | Fakultni nemocnice v Motole | Praha 5, 150 06, Czech Republic |
Completed | FN Brno - Detska nemocnice | Brno, 613 00, Czech Republic |
Active, not recruiting | Istanbul Universitesi Istanbul Tip Fakultesi | Istanbul, 34093, Turkey |
Withdrawn | Center of Pediatric Hematology, Oncology and Immunology | Moscow, 117997, Russian Federation |
Active, not recruiting | Western Ukrainian Specialized Pediatric Medial Centre, Surgical Department | Lviv, 79035, Ukraine |
Completed | Governmental Noncommercial Institution "National Cancer Institute | Kyiv, 03022, Ukraine |
Withdrawn | Morozov Children's City Clinical Hospital | Moscow, 119049, Russian Federation |
Active, not recruiting | Women's and Children's Hospital | North Adelaide, 5006, Australia |
Primary Outcome
- Phase 1: Number of participants in an assigned dose cohort with treatment emergent adverse events (TEAEs) by grade assessed by NCI-CTCAE v 4.03 who experience a DLTDLT: Dose-limiting toxicity. NCI-CTCAE: National Cancer Institute-Common Terminology Criteria for Adverse Events.date_rangeTime Frame:From Day 1 to Day 28 of Cycle 1 (1 Cycle=28 days)
- Phase 1: Number of participants with TEAEsdate_rangeTime Frame:From first dose of larotrectinib up to 93 months
- Phase 1: Severity of TEAEsdate_rangeTime Frame:From first dose of larotrectinib up to 93 months
- Phase 2: Overall response rate (ORR) by IRRCProportion of participants with a best overall response of complete response (CR) or partial response (PR) as determined by an independent radiology review committee (IRRC) based on Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, Response Assessment in Neuro Oncology (RANO) or International Neuroblastoma Response Criteria (INRC) as appropriate to tumor type who express NTRK gene fusions.date_rangeTime Frame:From first dose of Larotrectinib to disease progression or subsequent therapy or surgical intervention or death, up to 76 months
Secondary Outcome
- Phase 1: Maximum concentration of larotrectinib in plasma (Cmax)date_rangeTime Frame:Cohort 1 and 2: Cycle 1 Day 1 (C1D1) at 1 and 4 hours post-dose and C2D1 at pre-dose, and at 1 and 4 hours post-dose; Cohort 3 and Dose Expansion Cohort: C1D1 at 1 and 4 hours post-dose and C4D1 at pre-dose, 1 and 4 hours post-dose
- Phase 1: Area under the concentration versus time curve from time 0 to t (AUC0–t) of larotrectinib in plasmadate_rangeTime Frame:Cohort 1 and 2: C1D1 at 1 and 4 hours post-dose and C2D1 at pre-dose, and at 1 and 4 hours post-dose; Cohort 3 and Dose Expansion Cohort: C1D1 at 1 and 4 hours post-dose and C4D1 at pre-dose, 1 and 4 hours post-dose
- Phase 1: Oral clearance (CL/F)date_rangeTime Frame:Cohort 1 and 2: C1D1 at 1 and 4 hours post-dose and C2D1 at pre-dose, and at 1 and 4 hours post-dose; Cohort 3 and Dose Expansion Cohort: C1D1 at 1 and 4 hours post-dose and C4D1 at pre-dose, 1 and 4 hours post-dos
- Phase 1: Cerebral spinal fluid/plasma ratio of larotrectinibdate_rangeTime Frame:C1D1 in conjunction with the post-dose 1-hour PK sample
- Phase 1: Maximum tolerated dose (MTD)date_rangeTime Frame:From C1D1 to C1D28 of treatment of each participant in each of the assigned dose cohort, up to 16 months
- Phase 1: Recommended dose for Phase 2date_rangeTime Frame:From the date a participants from assigned Cohort was administered the first dose to the date of the last dose for the last patient from the dose escalation phase, up to 16 months
- Phase 1: Overall Response Rate (ORR)Proportion of participants with best overall response (BOR) of CR and PR; PFS, CBR and maximum change in tumor burden as assessed based on RECIST 1.1, INRC or RANO as appropriate for tumor type by IRRC.date_rangeTime Frame:From first dose of Larotrectinib to disease progression or subsequent therapy or surgical intervention or death (due to any cause), up to 93 months
- Phase 1: Mean change from baseline in Pain scores as assessed by the Wong-Baker Faces scaleWong-Baker Faces Scale giving a pain scale between 0 (no hurt) to 10 (hurts worst).date_rangeTime Frame:Baseline and D1 of every cycle (1 Cycle=28 days), up to 93 months
- Phase 1: Mean change in Health-related quality of life scores by PedsQL-CoreThe health-related quality of life (HRQoL) is assessed with the Pediatrics Quality of Life - Core Module (PedsQL-Core) questionnaire that consists of various age-related items regarding physical, emotional, social and school functioning and gives an overall score between 0 (highest HRQoL) and 144 (lowest HRQoL).date_rangeTime Frame:Baseline and D1 of every cycle (1 Cycle=28 days), Up to 93 months
- Phase 2: Best overall response (BOR)Participants with best overall response (BOR) of either CR or PR determined by Investigator’s or IRC's response assessment based on RANO, INRC and RECIST 1.1 as appropriate for tumor typedate_rangeTime Frame:From first dose of Larotrectinib to disease progression or subsequent therapy or surgical intervention or death (due to any cause), up to 76 months
- Phase 2: Duration of response (DOR)DOR determined by 1) an independent radiology review committee and 2) the treating Investigator.date_rangeTime Frame:From start of first objective response of confirmed CR or PR to progression or death (due to any cause), up to 76 months
- Phase 2: Proportion of patients with any tumor regression (i.e., any decrease from baseline of the longest diameters of target lesions) as a best responsedate_rangeTime Frame:From first dose of Larotrectinib, up to 76 months
- Phase 2: Progression-free survival (PFS)date_rangeTime Frame:From first dose of Larotrectinib to disease progression or subsequent therapy or surgical intervention or death (due to any cause), up to 112 months
- Phase 2: Overall survival (OS)date_rangeTime Frame:From first dose of Larotrectinib to death (due to any cause), up to 112 months
- Phase 2: Number of participants with Treatment emergent adverse events (TEAEs)date_rangeTime Frame:From first dose of larotrectinib to discontinuation of treatment or death (due to any cayse), up to 112 months
- Phase 2: Severity of adverse events as assessed by NCI-CTCAE grading V 4.03date_rangeTime Frame:From first dose of larotrectinib to discontinuation of treatment or death (due to any cause), up to 112 months
- Phase 2: Clinical Benefit Rate (CBR)CBR (i.e., best overall response of CR, PR or SD lasting 16 weeks or more as determined by 1) an independent radiology review committee (IRC) and 2) by the treating Investigator.date_rangeTime Frame:From first dose of Larotrectinib to disease progression or subsequent therapy or surgical intervention or death (due to any cause), up to 76 months
- Phase 2: Concordance coefficientConcordance coefficient of intra-patient molecular profiledate_rangeTime Frame:From baseline/screening and if feasible end of treatment (EOT) and or PD and or at re-start of study treatment following a "drug holiday" and disease recurrence, up to 112 months
- Phase 2: Post-operative tumor stagingPost-operative stage in patients treated with larotrectinib according to the TNM Classification of malignant tumors of the Union for International Cancer Control (UICC).date_rangeTime Frame:From first dose of Larotrectinib to surgical intervention, up to 112 months
- Phase 2: Post-operative surgical margin assessmentSurgical margin status in patients treated with larotrectinib using the International Cancer Control (UICC)-R classification and the Intergroup Rhabdomyosarcoma Staging (IRS) systems.date_rangeTime Frame:From first dose of Larotrectinib to surgical intervention, up to 112 months
- Phase 2: Pre-treatment surgical plan to preserve function and cosmetic outcomeDescriptive analysis of pretreatment surgical plan.date_rangeTime Frame:From first dose of Larotrectinib to surgical intervention, up to 112 months
- Phase 2: Post-treatment plans to conserve function and cosmetic outcomeDescriptive analysis of post-treatment plansdate_rangeTime Frame:From surgical intervention to subsequent therapy, up to 112 months
Trial design
Trial Type
InterventionalIntervention Type
DrugTrial Purpose
TreatmentAllocation
Non-randomizedBlinding
N/AAssignment
Parallel AssignmentTrial Arms
6