WithdrawnNCT05222165NEWELUpdated Feb 23, 2023

Study With Infigratinib in Subjects With Advanced Solid and CNS Tumors or Recurrent or Progressive Low-Grade Glioma With Selected FGFR1-3 Alterations

A Phase 1/2 interventional study of Infigratinib in Advanced Solid Tumor, CNS Tumor and Recurrent WHO Grade II Glioma, sponsored by Helsinn Healthcare SA. Withdrawn at 10 sites in 3 countries. Open to participants aged 3 Years and older. Per ClinicalTrials.gov, last updated 2023-02-23.

Sponsored by Helsinn Healthcare SA · Phase 1/2, Interventional, and Treatment

Why this study was withdrawn

The company decided to interrupt the development of the drug in all oncological indications

Phase: Phase 1/2
Study type: Interventional
Enrollment: 0
Allocation: Not applicable
Ages: 3 Years and older
Sex: All

Study 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.

Read the 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).

Conditions studied

Advanced Solid Tumor
CNS Tumor
Recurrent WHO Grade II Glioma

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Keywords

Low-Grade Glioma
FGFR1-3 Mutation or fusion/rearrangements
FGFR1-3 Fusion
FGFR1-3 Rearrangements
Advanced Solid Tumor
CNS Tumor

Who can participate

Ages eligible: 3 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 0 participants (actual)

Study arms

Experimental
Infigratinib (BGJ398)
Generic name: infigratinib. Dosage forms: 18mg and 25mg sprinkle capsules and 25mg, 75mg, 100mg capsules. Phase 1b Three dose levels escalation until RP2D is determined. Phase 2 * Pediatric patients: dose defined in the phase 1b (RP2D); * Adults: 125 mg. Frequency: once daily for 21 days in each 28-day treatment cycle. Duration: Treatment duration will last up to 26 cycles unless progression, death or unacceptable toxicity occur.
Drug: Infigratinib

Interventions

DrugInfigratinib
Hard gelatin capsules for oral use
Also known as: BGJ398

What researchers measure

Primary outcomes

Phase 1b Dose Limiting Toxicity (DLT) rate
An adverse event (AE) or abnormal laboratory value that are not clearly due to the underlying disease or extraneous causes, including those AEs and abnormal laboratory values that result in a failure to meet the criteria for re-treatment.
Time frame: 28 days
Phase 2 Objective Response Rate (ORR) by Blinded Independent Central Review (BICR)
The proportion of subjects who achieve a confirmed complete response (CR), confirmed partial response (PR), or confirmed minor response (MR) for subjects with LGG. For other subjects, ORR is defined as proportion of subjects who achieve a confirmed CR or confirmed PR.
Time frame: Up to 24 months

Secondary outcomes

Phase 1b Pharmacokinetics (PK): Cmax
The maximum observed plasma concentration after drug administration (defined as the 2-hour post-dose concentration)
Time frame: Up to 24 months
Phase 1b Pharmacokinetics (PK): AUC
Area under the plasma concentration-time curve
Time frame: Up to 24 months
Phase 1b Pharmacokinetics (PK): T1/2
Apparent terminal Half-Life
Time frame: Up to 24 months
Phase 1b Pharmacokinetics (PK): Tmax
Peak time
Time frame: Up to 24 months
Phase 1b Pharmacokinetics (PK): CL/F
Apparent clearance Day1
Time frame: Up to 24 months
Phase 1b Pharmacokinetics (PK): Vz/F
Apparent volume of distribution
Time frame: Up to 24 months
Phase 1b Best Overall Response (BOR) assessed by Investigator
The best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation.
Time frame: Up to 24 months
Phase 1b Disease Control Rate (DCR) assessed by Investigator
The proportion of subjects with a Best Overall Response (BOR) of complete response (CR), partial response (PR), minor response (MR) or standard deviation (SD) for subjects with LGG. For other subjects, DCR is defined as the proportion of subjects with a BOR of CR, PR or SD.
Time frame: Up to 24 months
Phase 1b Objective Response Rate (ORR) assessed by Investigator
Time frame: Up to 24 months
Phase 1b Duration of Response (DOR) assessed by Investigator
The time from first documentation of objective response (partial response (PR), complete response (CR), minor response (MR)) to first documentation of PD or death due to any cause, whichever occurs first.
Time frame: Up to 24 months
Phase 1b Time to Response (TTR) assessed by Investigator
The time from the date of the start of the treatment to the date of the first documented objective response (partial response (PR), complete response (CR), minor response (MR)) which is subsequently confirmed.
Time frame: Up to 24 months
Phase 1b Progression Free Survival (PFS) assessed by Investigator
The time from the date of the start of treatment to the date of the first documented progression or death due to any cause, whichever is earlier.
Time frame: Up to 24 months
Post-treatment termination Phase 1b Progression Free Survival (PFS) assessed by Investigator
PFS after treatment termination is the time from the date of treatment interruption for any reason excluding progression disease (PD) to the date of the first documented progression or death due to any cause, whichever is earlier.
Time frame: After treatment termination up to progression disease (PD), assessed for further 24 months
Phase 1b Best change in tumor size assessed by Investigator
The minimum change from baseline in the sum of diameters of target lesions.
Time frame: Up to 24 months
Phase 2 Duration of Response (DOR) assessed by blinded independent central review (BICR)
Time frame: Up to 24 months
Phase 2 Time to Response (TTR) assessed by blinded independent central review (BICR)
Time frame: Up to 24 months
Phase 2 Progression Free survival (PFS) assessed by blinded independent central review (BICR)
Time frame: 6 months from treatment initiation
Phase 2 Progression Free survival (PFS) assessed by blinded independent central review (BICR)
Time frame: 12 months from treatment initiation
Phase 2 Progression Free survival (PFS) assessed by blinded independent central review (BICR)
Time frame: 24 months from treatment initiation
Post-treatment termination Phase 2 Progression Free survival (PFS) assessed by blinded independent central review (BICR)
Time frame: After treatment termination up to progression disease (PD), assessed for further 24 months
Phase 2 Overall Survival (OS)
Overall Survival (OS) is defined as the time from the date of start of treatment to the date of death due to any cause.
Time frame: 12 months
Phase 2 Overall Survival (OS)
Time frame: 24 months
Phase 2 Best Overall Response (BOR) assessed by blinded independent central review (BICR)
Time frame: Up to 24 months
Phase 2 Disease Control Rate (DCR) assessed by blinded independent central review (BICR)
Time frame: Up to 24 months
Phase 2 Best change in tumor size assessed by blinded independent central review (BICR)
Time frame: Up to 24 months
Phase 2 Best Overall Response (BOR) assessed by Investigator
Time frame: Up to 24 months
Phase 2 Disease Control Rate (DCR) assessed by Investigator
Time frame: Up to 24 months
Phase 2 Objective Response Rate (ORR) assessed by Investigator
Time frame: Up to 24 months
Phase 2 Duration of Response (DOR) assessed by Investigator
Time frame: Up to 24 months
Phase 2 Time to Response (TTR) assessed by Investigator
Time frame: Up to 24 months
Phase 2 Progression Free Survival (PFS) assessed by Investigator
Time frame: Up to 24 months
Phase 2 Best change in tumor size assessed by Investigator
Time frame: Up to 24 months
Post-treatment termination Phase 2 Progression Free Survival (PFS) assessed by Investigator
Time frame: After treatment termination up to progression disease (PD), assessed for further 24 months
Phase 1b Incidence/severity of Adverse Events (AEs)
Number of patients who experienced AEs to assess the safety and tolerability of infigratinib in subjects with recurrent or progressive LGG.
Time frame: Up to 30 days after treatment termination
Phase 2 Incidence/severity of Adverse Events (AEs)
Time frame: Up to 30 days after treatment termination
Phase 1b Incidence/severity of Serious Adverse Events (SAEs)
Number of patients who experienced SAEs to assess the safety and tolerability of infigratinib in subjects with recurrent or progressive LGG.
Time frame: Up to 30 days after treatment termination
Phase 2 Incidence/severity of Serious Adverse Events (SAEs)
Time frame: Up to 30 days after treatment termination

Study locations

10 sites

Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California 94304, United States
Children's National Hospital - Brain Tumor Institute
Washington, District of Columbia 20010-2916, United States
Nicklaus Children's Hospital
Miami, Florida 33155, United States
Memorial Sloan Kettering Cancer Center
New York, New York 10065, United States
Duke Cancer Institute (DCI) - The Preston Robert Tisch Brain Tumor Center
Durham, North Carolina 27702-3624, United States
UPCM - Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania 15224-1529, United States
University of Alberta - Stollery Children's Hospital (SCH)
Edmonton, Alberta T6G 2B7, Canada
McMaster Children's Hospital (MCH)
Hamilton, Ontario L8N 3Z5, Canada
University of Toronto - The Hospital for Sick Children (SickKids)
Toronto, Ontario M5G 1X8, Canada
Universitaetsklinikum Heidelberg (UKHD) - Zentrum fuer Kinder- und Jugendmedizin - Klinik Kinderheilkunde III
Heidelberg, Baden-Wuerttemberg 69120, Germany

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

Registry details

Key details

Study ID: NCT05222165
Lead sponsor: Helsinn Healthcare SA
Collaborators: Labcorp Corporation of America Holdings, Inc
Responsible party: Sponsor
First posted: Feb 3, 2022
Start date: Oct 1, 2021
Primary completion: Dec 16, 2022
Completion: Dec 16, 2022
Last update: Feb 23, 2023

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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