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Advanced Solid TumorPhase 1/2NEWELNCT05222165

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 study testing Infigratinib in people with Advanced Solid Tumor and CNS Tumor, run by Helsinn Healthcare SA at 10 sites in 3 countries.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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 more about this study

Who is it for?
Ages 3 years and older
What is being tested?
Infigratinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
10 sitesin 3 countries
Study dates
1 Oct 2021to 16 Dec 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Phase 1b:
  • Subject must be ≥ 3 to <18 years of age at the Screening visit.
  • Confirmed diagnosis of one of the following:
  • 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
  • Histologically/cytologically confirmed CNS tumor (other than LGG).
  • Histologically/cytologically confirmed advanced solid tumor.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

10 sites in 3 countries.

10 sites in 3 countries

United States6 sites

  • Duke Cancer Institute (DCI) - The Preston Robert Tisch Brain Tumor Center

    Durham, North Carolina, 27702-3624

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Lucile Packard Children's Hospital at Stanford University Medical Center

    Palo Alto, California, 94304

  • UPCM - Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15224-1529

  • Children's National Hospital - Brain Tumor Institute

    Washington D.C., District of Columbia, 20010-2916

Other trials in United States

Canada3 sites

  • University of Alberta - Stollery Children's Hospital (SCH)

    Edmonton, Alberta, T6G 2B7

  • McMaster Children's Hospital (MCH)

    Hamilton, Ontario, L8N 3Z5

  • University of Toronto - The Hospital for Sick Children (SickKids)

    Toronto, Ontario, M5G 1X8

Other trials in Canada

Germany1 site

  • Universitaetsklinikum Heidelberg (UKHD) - Zentrum fuer Kinder- und Jugendmedizin - Klinik Kinderheilkunde III

    Heidelberg, Baden-Wurttemberg, 69120

Other trials in Germany

About this study

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)

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).

Being tested
Infigratinib
Keywords
Low-Grade Glioma, FGFR1-3 Mutation or fusion/rearrangements, FGFR1-3 Fusion, FGFR1-3 Rearrangements, Advanced Solid Tumor, CNS Tumor
Medical subject headings
Central Nervous System Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • InfigratinibDrug

    Also called BGJ398

    Hard gelatin capsules for oral use

Study groups in NCT05222165
Study groupRoleWhat they receive
Infigratinib (BGJ398)ExperimentalGeneric 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.
Receives: Drug: Infigratinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 28 days

  2. 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.

    Measured: Up to 24 months

Secondary outcomes (37)

  1. Phase 1b Pharmacokinetics (PK): Cmax

    The maximum observed plasma concentration after drug administration (defined as the 2-hour post-dose concentration)

    Measured: Up to 24 months

  2. Phase 1b Pharmacokinetics (PK): AUC

    Area under the plasma concentration-time curve

    Measured: Up to 24 months

  3. Phase 1b Pharmacokinetics (PK): T1/2

    Apparent terminal Half-Life

    Measured: Up to 24 months

  4. Phase 1b Pharmacokinetics (PK): Tmax

    Peak time

    Measured: Up to 24 months

  5. Phase 1b Pharmacokinetics (PK): CL/F

    Apparent clearance Day1

    Measured: Up to 24 months

  6. Phase 1b Pharmacokinetics (PK): Vz/F

    Apparent volume of distribution

    Measured: Up to 24 months

  7. 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.

    Measured: Up to 24 months

  8. 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.

    Measured: Up to 24 months

  9. Phase 1b Objective Response Rate (ORR) assessed by Investigator

    Measured: Up to 24 months

  10. 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.

    Measured: Up to 24 months

  11. 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.

    Measured: Up to 24 months

  12. 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.

    Measured: Up to 24 months

  13. 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.

    Measured: After treatment termination up to progression disease (PD), assessed for further 24 months

  14. Phase 1b Best change in tumor size assessed by Investigator

    The minimum change from baseline in the sum of diameters of target lesions.

    Measured: Up to 24 months

  15. Phase 2 Duration of Response (DOR) assessed by blinded independent central review (BICR)

    Measured: Up to 24 months

  16. Phase 2 Time to Response (TTR) assessed by blinded independent central review (BICR)

    Measured: Up to 24 months

  17. Phase 2 Progression Free survival (PFS) assessed by blinded independent central review (BICR)

    Measured: 6 months from treatment initiation

  18. Phase 2 Progression Free survival (PFS) assessed by blinded independent central review (BICR)

    Measured: 12 months from treatment initiation

  19. Phase 2 Progression Free survival (PFS) assessed by blinded independent central review (BICR)

    Measured: 24 months from treatment initiation

  20. Post-treatment termination Phase 2 Progression Free survival (PFS) assessed by blinded independent central review (BICR)

    Measured: After treatment termination up to progression disease (PD), assessed for further 24 months

  21. 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.

    Measured: 12 months

  22. Phase 2 Overall Survival (OS)

    Measured: 24 months

  23. Phase 2 Best Overall Response (BOR) assessed by blinded independent central review (BICR)

    Measured: Up to 24 months

  24. Phase 2 Disease Control Rate (DCR) assessed by blinded independent central review (BICR)

    Measured: Up to 24 months

  25. Phase 2 Best change in tumor size assessed by blinded independent central review (BICR)

    Measured: Up to 24 months

  26. Phase 2 Best Overall Response (BOR) assessed by Investigator

    Measured: Up to 24 months

  27. Phase 2 Disease Control Rate (DCR) assessed by Investigator

    Measured: Up to 24 months

  28. Phase 2 Objective Response Rate (ORR) assessed by Investigator

    Measured: Up to 24 months

  29. Phase 2 Duration of Response (DOR) assessed by Investigator

    Measured: Up to 24 months

  30. Phase 2 Time to Response (TTR) assessed by Investigator

    Measured: Up to 24 months

  31. Phase 2 Progression Free Survival (PFS) assessed by Investigator

    Measured: Up to 24 months

  32. Phase 2 Best change in tumor size assessed by Investigator

    Measured: Up to 24 months

  33. Post-treatment termination Phase 2 Progression Free Survival (PFS) assessed by Investigator

    Measured: After treatment termination up to progression disease (PD), assessed for further 24 months

  34. 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.

    Measured: Up to 30 days after treatment termination

  35. Phase 2 Incidence/severity of Adverse Events (AEs)

    Measured: Up to 30 days after treatment termination

  36. 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.

    Measured: Up to 30 days after treatment termination

  37. Phase 2 Incidence/severity of Serious Adverse Events (SAEs)

    Measured: Up to 30 days after treatment termination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Feb 2022
  2. Study start1 Oct 2021
  3. Primary completion16 Dec 2022
  4. Study completion16 Dec 2022

Why it stopped: The company decided to interrupt the development of the drug in all oncological indications

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Phase 1b: Rolling 6 design, 3 cohorts Phase 2: Single Group Assignment
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05222165
Sponsor's protocol ID
INFI-21-07
Other IDs
2021-005614-34
Acronym
NEWEL
Status last verified
Feb 2023
First submitted
12 Jan 2022
Last updated
23 Feb 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Infigratinib in people with Advanced Solid Tumor and CNS Tumor, run by Helsinn Healthcare SA at 10 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 23 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, Canada, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b Dose Limiting Toxicity (DLT) rate (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05222165.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2023.

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