A Phase 1/2 Study on the effects of the LOXO-292 (study drug) in Pediatric Patients with Advanced Solid or Primary Central Nervous System Tumors

Phase 1

• Conditions: Pediatric Patients with Advanced RET-Altered Solid or Primary Central Nervous System Tumors; 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: 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: LLTClassification code 10049516Term: Malignant tumorSystem 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; MedDRA version: 21.1Level: PTClassification code 10027105Term: Medullary thyroid cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-000212-28-IT
• Lead Sponsor: OXO ONCOLOGY INCORPORATED

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-21
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Pediatric patients major= 12 years of age and minor= 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.
2. Evidence of an activating RET gene alteration in tumor and/or blood as identified through molecular assays, as performed for clinical evaluation.
3. 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
4. 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.
5. 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).
6. Must have measurable or evaluable disease.
7. Karnofsky (patients 16 years and older) or Lansky (patients younger than 16 years) performance score of at least 50.
8. Must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy to CTCAE (v5.0) Grade minor= 2.
9. An archival (FFPE or fresh frozen) or fresh tumor tissue sample must be available (refer to Section 7.5 of the protocol)
10. Adequate hematologic status, defined as:
a) Absolute neutrophil count (ANC) major =1.0× 10^9/L not requiring growth factor support for at least 7 days prior to treatment
b) Platelet count major= 75 × 10^9/L not requiring transfusion support for at least 7 days prior to treatment
c) Hemoglobin (Hb) major= 8 mg/dL not requiring transfusion support or erythropoietin for at least 7 days prior to treatment
11. Adequate hepatic/pancreatic function, defined as:
a) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) minor= 2.5 × the upper limit of normal (ULN) or minor= 5 × ULN with documented liver involvement (such as liver metastasis or a primary biliary tumor),
and
b) Total bilirubin minor= 1.5 × ULN or minor=3×ULN with documented liver involvement or Gilbert's Disease (patients with Gilbert's Disease may be enrolled with prior Sponsor approval) and
c) Pancreatic lipase minor=1.5 × ULN (or Sponsor's approval).
12. Adequate renal function, defined as:
a) Estimated glomerular filtration rate major= 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 3.
13. Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation.
14. Willingness of male and female patients with reproductive potential to utilize double effective birth control methods
15. Ability to swallow capsules, liquid suspension, or gastric access via a naso- or gastric tube.
16. Parent/guardian of child or adolescent patient has the ability to understand, agree to, and sign the study Infor

Exclusion Criteria

1. Major surgery within 4 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 QT interval corrected for heart rate (QTc) interval major 440 milliseconds for patients minor= 15 years old and major 470 milliseconds for patients major 15 years old. For patients minor= 15 years old, Bazett's Formula will be utilized to determine QTc. For patients major 15 years old, either method, Fridericia or Bazett's Formula may be applied.
3. 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.
4. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
5. Pregnancy or lactation.
6. Uncontrolled hypotension or hypertension major= Grade 3 CTCAE (v 5.0).
7. Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the patient required a modification to current thyroid medication in the 7 days before start of selpercatinib).
8. Uncontrolled symptomatic hypercalcemia or hypocalcemia.
9. Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers (refer to Appendix D of the main protocol for examples).
10. 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.
11. Current treatment with proton pump inhibitors (PPIs).
12. Prior treatment with a selective RET inhibitor(s) (including investigational selective RET inhibitor[s]).
Note: Patients who discontinue another selective RET inhibitor(s) due to intolerance may be eligible with prior Sponsor approval.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified