SELPERCATINIB for RET-altered solid tumors | Primary central nervous system tumors

Inclusion criteria

• {"criterion_text":"- Pediatric patients ≥ 12 years of age and ≤ 21 years of age at Cycle 1 Day 1 (C1D1) with a locally advanced or metastatic solid or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and/or for which no standard or available systemic curative therapy exists. a) Patients with locally advanced disease who would require, in the opinion of the Investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection, are also eligible. b) In geographies where a selective RET-inhibitor is approved, patients may enroll without prior systemic treatment.\n- Adequate hematologic/pancreatic status, defined as: a) Absolute neutrophil count (ANC) ≥ 1.0× 10^9/L not requiring growth factor support for at least 7 days prior to treatment. b) Platelet count ≥ 75 × 10^9/L not requiring transfusion support for at least 7 days prior to treatment. c) Hb ≥ 8 mg/dL not requiring transfusion support or erythropoietin for at least 7 days prior to treatment.\n- Adequate hepatic/pancreatic function, defined as: a) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × the upper limit of normal (ULN) or ≤ 5 × ULN with documented liver involvement (such as liver metastasis or a primary biliary tumor), and b) Total bilirubin ≤ 1.5 × ULN or ≤ 3 × ULN with documented liver involvement (patients with Gilbert's Disease may be enrolled with prior Sponsor approval)\n- Adequate renal function, defined as: a) Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 based on local institutional practice for determination, or a maximum serum creatinine by age and gender as presented in Synopsis Table 2.\n- Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation.\n- Willingness of male and female patients with reproductive potential to utilize double effective birth control methods\n- Ability to swallow capsules, liquid suspension, or gastric access via a naso- or gastric tube.\n- The patient and, when applicable, the parent/guardian of child or adolescent patient has the ability to understand, agree to, and sign the study Informed Consent Form (ICF) and applicable Pediatric Assent Form before initiation of any protocol-related procedures; patient has the ability to give assent, as applicable, at the time of parental/guardian consent.\n- Evidence of an activating RET gene alteration in tumor and/or blood as identified through molecular assays, as performed for clinical evaluation.\n- Patients with primary CNS tumors or cerebral metastasis: a) Must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment b) Must have not required increasing doses of steroids within the 7 days prior to enrollment to manage CNS symptoms\n- Imaging study must be performed within 28 days of C1D1 while on stable dose steroid medication (if needed) for at least 7 days immediately before the imaging study.\n- Histologic verification of malignancy at original diagnosis or relapse, except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebral spinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or betahuman chorionic gonadotropin (HCG).\n- Must have measurable or non-measurable but evaluable disease.\n- Karnofsky (patients 16 years and older) or Lansky (patients younger than 16 years) performance score of at least 50.\n- Must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy to CTCAE (v5.0) Grade ≤ 2.\n- An archival (FFPE or fresh frozen) or fresh tumor tissue sample must be available (refer to Section 7.5 of the protocol)."}

Exclusion criteria

• {"criterion_text":"- Major surgery within 2 weeks prior to C1D1\n- Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to C1D1; ongoing cardiomyopathy; or current prolonged QT interval corrected for heart rate (QTc) interval > 440 milliseconds for patients ≤ 15 years old and > 470 milliseconds for patients > 15 years old. For patients ≤ 15 years old, Bazett's Formula will be utilized to determine QTc. For patients > 15 years old, either method, Fridericia or Bazett's Formula may be applied.\n- Active uncontrolled systemic bacterial, viral, or fungal infection, which in the opinion of the Investigator makes the risk: benefit ratio for the patient to participate in the trial unfavorable.\n- Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.\n- Pregnancy or lactation.\n- Uncontrolled hypotension or hypertension ≥ Grade 3 CTCAE (v 5.0).\n- Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the patient required a modification to current thyroid medication in the 7 days before start of selpercatinib).\n- Uncontrolled symptomatic hypercalcemia or hypocalcemia.\n- Known hypersensitivity to any of the components of the investigational agent, selpercatinib or Ora-Sweet® SF and OraPlus®, for patients who will receive selpercatinib suspension."}

Primary endpoints

• {"endpoint_text":"- PHASE 1 Frequency, severity and relatedness of TEAEs and SAEs, including DLTs in pediatric patients receiving selpercatinib\n- PHASE 2 ORR based on RECIST v 1.1 or RANO as appropriate to tumor type as determined by an IRC","definition_or_measurement_approach":"Phase 1: safety assessed by frequency, severity and relatedness of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including dose-limiting toxicities (DLTs).\nPhase 2: Objective response rate (ORR) determined by an Independent Review Committee (IRC) using RECIST v1.1 for solid tumors or RANO criteria for CNS tumors, measured as proportion of patients with best overall confirmed response of complete response (CR) or partial response (PR)."}

Methods

• Patient referral, recruitment, screening and/or retention provided by Medpace Inc. (contact: m.baptist@medpace.com) — duties listed: Patient Referral, Recruitment, Screening and/or Retention, Site Readiness, Site Selection
• Patient referral, recruitment, screening and/or retention provided by Unisphere Travel Ltd. Inc. (contact: jbrown@colpittsclinical.com) — duties listed: Patient Referral, Recruitment, Screening, and/or Retention

Denmark

Earliest CTIS Part Ii Submission Date

23-05-2024

Latest Decision Or Authorization Date

18-06-2024

Processing Time Days

26

Number Of Sites

1

Number Of Participants

3

Germany

Earliest CTIS Part Ii Submission Date

23-05-2024

Latest Decision Or Authorization Date

21-06-2024

Processing Time Days

29

Number Of Sites

1

Number Of Participants

5

France

Earliest CTIS Part Ii Submission Date

23-05-2024

Latest Decision Or Authorization Date

02-03-2026

Processing Time Days

648

Number Of Sites

1

Number Of Participants

10

Italy

Earliest CTIS Part Ii Submission Date

23-05-2024

Latest Decision Or Authorization Date

04-03-2026

Processing Time Days

650

Number Of Sites

1

Number Of Participants

2

Spain

Earliest CTIS Part Ii Submission Date

23-05-2024

Latest Decision Or Authorization Date

05-03-2026

Processing Time Days

651

Number Of Sites

1

Number Of Participants

5

Primary sponsor

Full Name

Loxo Oncology Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Medpace Inc.

Responsibilities

Patient Referral, Recruitment, Screening and/or Retention, Site Readiness, Site Selection

Name

Alturas Analytics Inc.

Responsibilities

sponsorDuties codes: 4

Name

Oracle America Inc.

Responsibilities

sponsorDuties codes: 6

Name

Mosaic Laboratories LLC

Responsibilities

sponsorDuties codes: 4

Name

Perceptive Informatics Inc.

Responsibilities

sponsorDuties codes: 4

Third parties

• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medpace Inc.","duties_or_roles":"Patient Referral, Recruitment, Screening and/or Retention, Site Readiness, Site Selection","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Alturas Analytics Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Oracle America Inc.","duties_or_roles":"sponsorDuties codes: 6","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Mosaic Laboratories LLC","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Unisphere Travel Ltd. Inc.","duties_or_roles":"Patient Referral, Recruitment, Screening, and/or Retention","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"sponsorDuties codes: 4","organisation_type":"Pharmaceutical company"}