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JOURNAL ONKOLOGIE – STUDIE
LIBRETTO-121

A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors

Rekrutierend

NCT-Nummer:
NCT03899792

Studienbeginn:
Juni 2019

Letztes Update:
16.07.2021

Wirkstoff:
LOXO-292

Indikation (Clinical Trials):
Sarcoma, Thyroid Neoplasms, Thyroid Cancer, Papillary, Fibrosarcoma, Myofibromatosis, Thyroid Diseases

Geschlecht:
Alle

Altersgruppe:
Kinder (0-17)

Phase:
-

Sponsor:
Loxo Oncology, Inc.

Collaborator:
Eli Lilly and Company

Studienleiter

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Study Director
Eli Lilly and Company

Kontakt

There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
Kontakt:
Phone: 1-317-615-4559
E-Mail: ClinicalTrials.gov@lilly.com
» Kontaktdaten anzeigen

Studienlocations
(3 von 24)

Alle anzeigen

Studien-Informationen

Detailed Description:

This study includes 2 parts: phase 1 (dose escalation) and phase 2 (dose expansion). In phase

1, participants will be enrolled using a rolling 6 dose escalation scheme. The starting dose

of LOXO-292 is equivalent to the adult recommended phase 2 dose of 160 milligrams (mg) twice

a day (BID). Once the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) is

identified, participants will be enrolled to one of four phase 2 dose expansion cohorts

depending on tumor histology and tumor genotype. Cycle length will be 28 days.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Advanced or metastatic solid or primary CNS tumor which has failed standard of care

therapies

- Evidence of an activating RET gene alteration in the tumor and/or blood

- Measurable or non-measurable disease

- Karnofsky (participants 16 years and older) or Lansky (participants younger than 16)

performance score of at least 50

- Participant with primary CNS tumors or cerebral metastases must be neurologically

stable for 7 days prior and must not have required increasing doses of steroids within

the last 7 days

- Adequate hematologic, hepatic and renal function.

- Ability to receive study drug therapy orally or via gastric access

- Willingness of men and women of reproductive potential to observe conventional and

effective birth control

Exclusion Criteria:

- Major surgery within two weeks prior to planned start of LOXO-292

- Clinically significant, uncontrolled cardiac, cardiovascular disease or history of

myocardial infarction within 6 months prior to planned start of LOXO-292

- Active uncontrolled systemic bacterial, viral, fungal or parasitic infection

- Clinically significant active malabsorption syndrome

- Pregnancy or lactation

- Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the participant

required a modification to current thyroid medication in the 7 days before start of

LOXO-292)

- Uncontrolled symptomatic hypercalcemia or hypocalcemia

- Known hypersensitivity to any of the components of the investigational agent, LOXO-292

or Ora-Sweet® SF and OraPlus®, for participants who will receive LOXO-292 suspension

- Prior treatment with a selective RET inhibitor(s) (including investigational selective

RET inhibitor[s])

Studien-Rationale

Primary outcome:

1. To Determine the Safety of Oral LOXO-292 in Pediatric Participants with Advanced Solid Tumors: Dose Limiting Toxicities (DLTs) (Time Frame - During the first 28-day cycle of LOXO-292 treatment):
For Phase 1

2. To Determine the Safety of Oral LOXO-292 in Pediatric Participants with Primary CNS Tumors: DLTs (Time Frame - During the first 28-day cycle of LOXO-292 treatment):
For Phase 1

3. Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per Independent Review Committee (IRC) (Time Frame - Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)):
For Phase 2

4. ORR Based on Response Assessment in Neuro-Oncology (RANO) per IRC (Time Frame - Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)):
For Phase 2

Secondary outcome:

1. Plasma Concentrations of LOXO-292 (Time Frame - Days 1 and 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days)):
Phase 1

2. Area Under the Concentration-Time Curve from 0 to 24 hours (AUC0-24) of LOXO-292 (Time Frame - Days 1 and 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days)):
Phase 1 and Phase 2

3. Maximum Concentration (Cmax) of LOXO-292 (Time Frame - Days 1 and 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days)):
Phase 1 and Phase 2

4. Time to Maximum Concentration (Tmax) of LOXO-292 (Time Frame - Days 1 and 8 of Cycle 1, Day 1 of Cycle 3 and Day 8 after Intra-participant Dose Escalation (each cycle is 28 days)):
Phase 1 and Phase 2

5. Recommended LOXO-292 Dose for Phase 2 (MTD) (Time Frame - Cycle 1 (28 days)):
For Phase 1

6. To Assess the Preliminary Anti-Tumor Activity of LOXO-292 in Pediatric Participants with Tumors Harboring an Activating RET Alteration as Determined by ORR Based on RECIST v1.1 (Time Frame - Baseline to Progressive Disease or Death due to any cause (Estimated up to 12 months)):
For Phase 1

7. Changes from Baseline in Pain Measures as Measured by Wong Baker Faces scales. Wong-Baker Faces Pain Scale includes pictures of facial expressions with correlating scores of 0 being 'no hurt' and 10 being 'hurts worst'. (Time Frame - Up to 24 months):
For Phase 1

8. Changes from Baseline in Health Related Quality of Life Measures as Measured by Pediatric Quality of Life (PedsQoL) Inventory Core. PedsQoL includes a list of problems with scores of 0 being 'never a problem' and 4 being 'almost always a problem'. (Time Frame - Up to 24 months):
For Phase 1

9. Objective Response Rate as Assessed by RECIST v1.1, as Assessed by Investigator (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.):
For Phase 2

10. Objective Response Rate as Assessed by RANO, as Assessed by Investigator (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.):
For Phase 2

11. Duration of Response (DOR) as Assessed by Investigator (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.):
For Phase 2

12. Duration of Response (DOR) as Assessed by the IRC (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.):
For Phase 2

13. Progression Free Survival (PFS) as Assessed by Investigator (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.):
For Phase 2

14. PFS as Assessed by IRC (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.):
For Phase 2

15. Overall survival (OS) (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, and 7 days after the last dose (for up to 2 years) in participants who have not progressed.):
For Phase 2

16. Clinical Benefit Rate (by Investigator) (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed.):
For Phase 2

17. Clinical Benefit Rate (by IRC) (Time Frame - Approximately every 8 weeks for one year, then every 12 weeks, 7 days after the last dose (for up to 2 years) in participants who have not progressed.):
For Phase 2

18. Frequency of Adverse Events (AEs) (Time Frame - From the time of informed consent, for approximately 24 months (or earlier if the participants discontinues from the study), and through Safety Follow-up (28 days after the last dose)):
For Phase 2

19. To Evaluate the Concordance of Prior Molecular that Detected a RET Alteration within the Participant's Tumor with Diagnostic Tests Being Evaluated by Sponsor (Time Frame - 6 months):
For Phase 2

20. Phase 2: Post-Operative Stage on Participants Treated with LOXO-292 (Time Frame - Up to 3 years):
Tumor stage is described according to the Tumor, Node, Metastasis (TNM)Classification of malignant tumors of the Union for International Cancer Control (UICC)

21. Phase 2: Surgical Margin Status in Participants Treated with LOXO-292 (Time Frame - Up to 3 years):
Tumor margins after surgery are classified into four groups using the International Cancer Control (UICC)-R classification and the Intergroup Rhabdomyosarcoma Staging (IRS) systems: 1) Complete tumor resection with histologically free margins, 2) Macroscopic resection but invaded margins on histology, 3)Macroscopic residual tumor and 4) Distant metastatic tumor.

22. Descriptive Analysis of Pretreatment Surgical Plan (Time Frame - Up to 3 years):
For Phase 2

23. Descriptive Analysis of Post-Treatment Plans (Time Frame - Up to 3 years):
For Phase 2

Geprüfte Regime

  • LOXO-292 (Selpercatinib / LY3527723 / ):
    Oral LOXO-292

Quelle: ClinicalTrials.gov


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