Clinical Trials /

Phase 1b Trial of BGJ398/BYL719 in Solid Tumors

NCT01928459

Description:

To study the safety and efficacy of the combination of BGJ398 with BYL719 in patients whose tumors express mutations to PIK3CA with or without alterations to FGFR 1-3.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT01928459

Trial Eligibility

Document

Title

  • Brief Title: Phase 1b Trial of BGJ398/BYL719 in Solid Tumors
  • Official Title: A Phase Ib, Open-label Study of Oral BGJ398 in Combination With Oral BYL719 in Adult Patients With Select Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: CBGJ398X2102
  • NCT ID: NCT01928459

Conditions

  • Advanced Solid Tumors
  • Metastatic Solid Tumors

Interventions

DrugSynonymsArms
BGJ398Dose escalation
BYL719Dose escalation

Purpose

To study the safety and efficacy of the combination of BGJ398 with BYL719 in patients whose tumors express mutations to PIK3CA with or without alterations to FGFR 1-3.

Detailed Description

      This dose escalation/dose expansion study will evaluate the combination of orally
      administered BGJ398 in combination with orally administered BYL719. During the dose
      escalation part, the MTD of the combination will be determined in patients whose advanced or
      metastatic tumors express mutations to PIK3CA. Once the MTD has been determined, the
      expansion part will begin. Patients will be addd to one of three arms based on the disease
      type and genetic changes. Patients with metastatic colorectal cancer are not eligible for
      participation in the expansion part.

Trial Arms

NameTypeDescriptionInterventions
Metastatic breast cancerExperimentalEvaluation of safety and efficacy in patients with metastatic breast cancer whose tumors contain mutations to PIK3CA and alterations FGFR 1-3.
  • BGJ398
  • BYL719
Solid tumor arm 1ExperimentalPatients with solid tumors (except for colorectal cancer) whose tumors express mutations to PIK3CA.
  • BGJ398
  • BYL719
Solid tumor arm 2ExperimentalPatients with solid tumors (except for colorectal cancer) whose tumomrs express mutations to PIK3CA and alterations to FGFR 1-3
  • BGJ398
  • BYL719
Dose escalationExperimentalTo determine the MTD or RDE of the combination of BGJ398 with BYL719 in patients with advanced or metastastic solid tumors that express mutations to PIK3CA.
  • BGJ398
  • BYL719

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically/cytologically confirmed advanced or metastatic solid tumors who have
             failed standard therapy or for whom no effective standard anti-cancer therapy exists

          -  Documented PIK3CA mutations in all patients in dose escalation and expansion with or
             without documented genetic alterations in FGFR depending upon dose expansion cohort
             (either local or central determination)

          -  Measurable disease defined by RECIST v1.1

          -  ECOG performance status of ≤2

        Exclusion Criteria:

          -  Prior PI3Ki or selective FGFR inhibitor treatment (for patients enrolled to expansion
             part)

          -  Colorectal cancer (for patients enrolled to expansion part)

          -  Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs
             or with fasting glucose ≥ 140 mg/dL / 7.8 mmol/L, history of clinically significant
             gestational diabetes mellitus or documented steroid-induced diabetes mellitus

          -  Use of medications that increase serum levels of phosphorus and/or calcium

          -  Inorganic phosphorus outside of normal limits

          -  Total and ionized serum calcium outside of normal limits
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence rate of dose limiting toxicities (DLTs) of the combination of BGJ398 with BYL719
Time Frame:Approximately 8 months
Safety Issue:
Description:The dose escalation part of the study will be guided by a well-established statistical method/model to estimate the maximum tolerated dose(s) and/or the recommended dose for expansion (RDE). Safety(incidence and nature of DLTs), pharmacokinetic and pharmacodynamic data will guide dose escalation decisioins.

Secondary Outcome Measures

Measure:Safety and tolerability of BGJ398/BYL719 combination at the recommended dose for expansion (RDE)
Time Frame:Every 28 days from baseline visit until end of study visit
Safety Issue:
Description:This will be assessed by looking at the number of Adverse Events (AEs), serious AEs (SAEs) changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions and reductions
Measure:Overall response rate
Time Frame:Every two months from the date of baseline CT scan
Safety Issue:
Description:Assessment of preliminary antitumor activity of the combination of BGJ398 with BYL719; Overall response rate = complete response + partial response
Measure:Progression free survival
Time Frame:Every two months from the date of baseline CT scan
Safety Issue:
Description:Assessment of preliminary antitumor activity of the combination of BGJ398 with BYL719
Measure:Time vs. concentration profile of BGJ398 and BYL719
Time Frame:Every 28 days for up to 10 cycles
Safety Issue:
Description:Plasma concentration versus time profiles. Plasma PK parameters will be used to characterize the PK profiles of the combination of BGJ398 with BYL719

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • BGJ398
  • BYL719
  • advanced solid tumor
  • metastatic breast cancer
  • PK3CA
  • FGFR
  • fibroblast growth factor receptor

Last Updated

December 9, 2020