Clinical trial NCT05222165: Study With Infigratinib in Subjects With Advanced Solid and CNS Tumors or Recurrent or Progressive Low-Grade Glioma With Selected FGFR1-3 Alterations
Official title: A Phase 1b/2, Multicenter, Open-Label Study of Oral Infigratinib in Pediatric Subjects With Advanced Solid and Central Nervous System (CNS) Tumors (Phase 1b) and in Subjects With Recurrent or Progressive Low-Grade Gliomas Harboring Selected FGFR1, FGFR2, or FGFR3 Alterations (Phase 2)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
CNS Tumor
Recurrent WHO Grade II Glioma
Keywords: Low-Grade Glioma
FGFR1-3 Mutation or fusion/rearrangements
FGFR1-3 Fusion
FGFR1-3 Rearrangements
Advanced Solid Tumor
CNS Tumor
Lead sponsor: Helsinn Healthcare SA
Sponsor class: INDUSTRY
Collaborators: name: Labcorp Corporation of America Holdings, Inc
First posted: 2022-02-03
Enrollment: 0
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase 1b: Rolling 6 design, 3 cohorts Phase 2: Single Group Assignment
Primary purpose: TREATMENT

Brief summary: The phase 1b study is aimed at determining the pediatric recommended phase 2 dose (RP2D) of Infigratinib.

The phase 2 study will evaluate efficacy and safety of infigratinib.

Detailed description: Phase 1b:

Pediatric subjects with advanced solid and CNS tumors or recurrent or progressive Low-Grade Glioma with selected FGFR1-3 alterations will follow a standard dose escalation, in 3 dose levels, to determine the pediatric recommended Phase 2 dose (RP2D) and to assess the safety.

Dose escalation decisions will be assessed through three dose level cohorts.

Phase 2:

To evaluate the efficacy and safety in Pediatric and adult subjects with LGG with selected FGFR1-3 alterations (including subjects who received infigratinib at the RP2D).

Eligibility criteria: Inclusion Criteria:

Phase 1b:

* Subject must be ≥ 3 to \<18 years of age at the Screening visit.
* Confirmed diagnosis of one of the following:

  1. LGG (WHO Grade I or II glioma) based on histology, molecular, and clinical criteria concordant with the WHO Grading of Tumors of the Central Nervous System, including glial or mixed neuronal-glial tumor
  2. Histologically/cytologically confirmed CNS tumor (other than LGG).
  3. Histologically/cytologically confirmed advanced solid tumor.
* Disease is recurrent or progressive after standard therapy (at least 1 prior standard therapy appropriate for tumor type and stage of disease unless available standard therapies are considered inadequate for the subject).

Phase 2 at screening:

* Diagnosis of recurrent or progressive (at least 1 prior standard therapy) LGG (WHO Grade I or II glioma), including glial or mixed neuronal-glial tumor, based on histology, molecular, and clinical criteria concordant with the WHO Grading of Tumors of the Central Nervous System.
* Age 3 years and older at screening visit.

Phase 1b/2 (all subjects) at screening:

* Able to swallow and retain oral medication.
* Willing to stop consumption of grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges, or products containing juice of these fruits; and have not consumed these within 7 days before the first dose of study drug.
* Willing and able to comply with scheduled visits, treatment plan, and laboratory tests.

Sex and Contraceptive/Barrier Requirements

* Contraceptive and barrier use as well as pregnancy testing is required as appropriate for the age and sexual activity of pediatric and adult subjects and as required by local regulations.
* Subjects can be male and female.
* A legal guardian or caregiver must be able to accurately maintain the pediatric subject's take-home record, including items of general health.

Exclusion Criteria:

* Prior treatment with a FGFR1-3 selective inhibitor.
* Known serious active infection or any clinically significant systemic illness, which in the Investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the subject's ability to tolerate the study drug.
* Received anti-convulsant drugs that are strong inducers of CYP3A4 (i.e., carbamazepine, phenobarbital, phenytoin) within 4 weeks before starting study treatment.
* Currently receiving treatment with agents that are known strong and moderate inducers of CYP3A4 within 4 weeks from start of treatment or inhibitors of CYP3A4 within 1 week from start of treatment, including herbal preparations; medications which increase serum phosphorus and/or calcium concentration; use of a proton-pump inhibitors (e.g., omeprazole) within 4 days prior to start of study therapy or H2 receptor antagonists (e.g., famotidine) within 2 days prior to the start of study therapy.
* Uncontrollable seizures.
* Have current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy; corneal abrasion, inflammation, or ulceration; or keratoconjunctivitis, confirmed by ophthalmic examination. Subjects with asymptomatic ophthalmic conditions assessed by the Investigator to pose minimal risk for study participation may be enrolled in the study.
* Have current evidence of endocrine alterations of calcium/phosphate homeostasis (e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis), unless well controlled.
* Have a history and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, vasculature, myocardium, and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, small renal cyst or stone calcifications, and asymptomatic coronary calcification.
* Have impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (e.g., active ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
* Had major surgery within 2 weeks of enrollment or not fully healed from open wound.

Primary outcomes:
measure: Phase 1b Dose Limiting Toxicity (DLT) rate
timeFrame: 28 days
measure: Phase 2 Objective Response Rate (ORR) by Blinded Independent Central Review (BICR)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Phase 1b Pharmacokinetics (PK): Cmax
timeFrame: Up to 24 months
measure: Phase 1b Pharmacokinetics (PK): AUC
timeFrame: Up to 24 months
measure: Phase 1b Pharmacokinetics (PK): T1/2
timeFrame: Up to 24 months
measure: Phase 1b Pharmacokinetics (PK): Tmax
timeFrame: Up to 24 months
measure: Phase 1b Pharmacokinetics (PK): CL/F
timeFrame: Up to 24 months
measure: Phase 1b Pharmacokinetics (PK): Vz/F
timeFrame: Up to 24 months
measure: Phase 1b Best Overall Response (BOR) assessed by Investigator
timeFrame: Up to 24 months
measure: Phase 1b Disease Control Rate (DCR) assessed by Investigator
timeFrame: Up to 24 months
measure: Phase 1b Objective Response Rate (ORR) assessed by Investigator
timeFrame: Up to 24 months
measure: Phase 1b Duration of Response (DOR) assessed by Investigator
timeFrame: Up to 24 months
measure: Phase 1b Time to Response (TTR) assessed by Investigator
timeFrame: Up to 24 months
measure: Phase 1b Progression Free Survival (PFS) assessed by Investigator
timeFrame: Up to 24 months
measure: Post-treatment termination Phase 1b Progression Free Survival (PFS) assessed by Investigator
timeFrame: After treatment termination up to progression disease (PD), assessed for further 24 months
measure: Phase 1b Best change in tumor size assessed by Investigator
timeFrame: Up to 24 months
measure: Phase 2 Duration of Response (DOR) assessed by blinded independent central review (BICR)
timeFrame: Up to 24 months
measure: Phase 2 Time to Response (TTR) assessed by blinded independent central review (BICR)
timeFrame: Up to 24 months
measure: Phase 2 Progression Free survival (PFS) assessed by blinded independent central review (BICR)
timeFrame: 6 months from treatment initiation
measure: Phase 2 Progression Free survival (PFS) assessed by blinded independent central review (BICR)
timeFrame: 12 months from treatment initiation
measure: Phase 2 Progression Free survival (PFS) assessed by blinded independent central review (BICR)
timeFrame: 24 months from treatment initiation
measure: Post-treatment termination Phase 2 Progression Free survival (PFS) assessed by blinded independent central review (BICR)
timeFrame: After treatment termination up to progression disease (PD), assessed for further 24 months
measure: Phase 2 Overall Survival (OS)
timeFrame: 12 months
measure: Phase 2 Overall Survival (OS)
timeFrame: 24 months
measure: Phase 2 Best Overall Response (BOR) assessed by blinded independent central review (BICR)
timeFrame: Up to 24 months
measure: Phase 2 Disease Control Rate (DCR) assessed by blinded independent central review (BICR)
timeFrame: Up to 24 months
measure: Phase 2 Best change in tumor size assessed by blinded independent central review (BICR)
timeFrame: Up to 24 months
measure: Phase 2 Best Overall Response (BOR) assessed by Investigator
timeFrame: Up to 24 months
measure: Phase 2 Disease Control Rate (DCR) assessed by Investigator
timeFrame: Up to 24 months
measure: Phase 2 Objective Response Rate (ORR) assessed by Investigator
timeFrame: Up to 24 months
measure: Phase 2 Duration of Response (DOR) assessed by Investigator
timeFrame: Up to 24 months
measure: Phase 2 Time to Response (TTR) assessed by Investigator
timeFrame: Up to 24 months
measure: Phase 2 Progression Free Survival (PFS) assessed by Investigator
timeFrame: Up to 24 months
measure: Phase 2 Best change in tumor size assessed by Investigator
timeFrame: Up to 24 months
measure: Post-treatment termination Phase 2 Progression Free Survival (PFS) assessed by Investigator
timeFrame: After treatment termination up to progression disease (PD), assessed for further 24 months
measure: Phase 1b Incidence/severity of Adverse Events (AEs)
timeFrame: Up to 30 days after treatment termination
measure: Phase 2 Incidence/severity of Adverse Events (AEs)
timeFrame: Up to 30 days after treatment termination
measure: Phase 1b Incidence/severity of Serious Adverse Events (SAEs)
timeFrame: Up to 30 days after treatment termination
measure: Phase 2 Incidence/severity of Serious Adverse Events (SAEs)
timeFrame: Up to 30 days after treatment termination
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital at Stanford University Medical Center
state: California
city: Washington
country: United States
facility: Children's National Hospital - Brain Tumor Institute
state: District of Columbia
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute (DCI) - The Preston Robert Tisch Brain Tumor Center
state: North Carolina
city: Pittsburgh
country: United States
facility: UPCM - Children's Hospital of Pittsburgh
state: Pennsylvania
city: Edmonton
country: Canada
facility: University of Alberta - Stollery Children's Hospital (SCH)
state: Alberta
city: Hamilton
country: Canada
facility: McMaster Children's Hospital (MCH)
state: Ontario
city: Toronto
country: Canada
facility: University of Toronto - The Hospital for Sick Children (SickKids)
state: Ontario
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg (UKHD) - Zentrum fuer Kinder- und Jugendmedizin - Klinik Kinderheilkunde III
state: Baden-Wuerttemberg
Study officials:
References: