BGJ398 for Patients With Tumors With FGFR Genetic Alterations (CBGJ398XUS04)

Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 6 - BGJ398 for Patients With Tumors With FGFR Genetic Alterations

The purpose of this signal seeking study was to determine whether treatment with BGJ398 demonstrates sufficient efficacy in select FGFR pathway-regulated solid tumors and/or hematologic malignancies to warrant further study.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor; Hematologic Malignancies
• Intervention / Treatment: Drug: BGJ398

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Alabama Oncology St. Vincent's Birmingham
  • California
    • Oceanside, California, United States, 92056
      • North County Oncology Medical Clinic Inc
    • San Francisco, California, United States, 94110
      • San Francisco General Hospital San Francisco Gen Hosp (7)
  • Colorado
    • Greenwood Village, Colorado, United States, 80304
      • Rocky Mountain Cancer Centers Rocky Mountain Cancer Ctr (50)
  • Connecticut
    • Norwalk, Connecticut, United States, 06856
      • Norwalk Hospital
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists Florida Cancer Specialists 36
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer
  • Georgia
    • Marietta, Georgia, United States, 30060
      • NorthWest Georgia Oncology Centers NW Georgia Oncology
    • Rome, Georgia, United States, 30165
      • Harbin Clinic Medical Oncology Clin. Res.
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Illinois Cancer Specialists
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital of Chicago Developmental Therapeutics
  • Indiana
    • Anderson, Indiana, United States, 46011
      • Community Clinical Research Center
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Indiana Univ. - Purdue Univ.
    • South Bend, Indiana, United States, 46617
      • Northern Indiana Cancer Research Consortium No. Indiana Cancer Res.
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville / James Graham Brown Cancer Center SC
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • St. Agnes Hospital St. Agnes Hospital (2)
  • Massachusetts
    • Fairhaven, Massachusetts, United States, 02719
      • Southcoast Centers for Cancer Care
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Cancer and Hematology Centers of West Michigan Dept. of Oncology
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hematology, P.A. Minnesota Oncology Hem (27)
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center Research Med Center (2)
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Billings Clinic (8)
  • New Hampshire
    • Bedford, New Hampshire, United States, 03110
      • Dartmouth Hitchcock Medical Center Dartmouth Hitchcock - Lebanon
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • New Mexico Cancer Center
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Waverly Hematology Oncology
    • Chapel Hill, North Carolina, United States, 27599-7600
      • University of N C at Chapel Hill Physician Office Building
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center Seeley G. Mudd Bldg.
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health Hem & Onc Medical Center
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Sanford Hematology Oncology
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care Inc Oncology Hematology Care 2
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation Taussig Cancer Institute
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland Seidman Cancer Center University Hospitals
  • Oregon
    • Bend, Oregon, United States, 97701
      • Bend Memorial Clinic Bend Mem. Clinic
    • Portland, Oregon, United States, 97210
      • Northwest Cancer Specialists Northwest Cancer
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Health Network
    • Philadelphia, Pennsylvania, United States, 19124
      • Cancer Treatment Centers of America Eastern Regional Medical Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute Hillman Cancer Center (2)
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital Rhode Island Hosp. (2)
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford University of South Dakota Medical Center Sanford Health
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology Tennessee Oncology (3)
  • Texas
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders
    • Houston, Texas, United States, 77030
      • Houston Methodist Cancer Center
    • Houston, Texas, United States, 77024
      • Oncology Consultants Oncology Group
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)
    • McAllen, Texas, United States, 78503
      • Texas Oncology
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy & Research Center UT Health Science Center Oncology Dept.
    • Waco, Texas, United States, 76712
      • Texas Oncology Cancer Care & Research Center Texas Oncology
    • Webster, Texas, United States, 77598
      • Deke Slayton Cancer Center Deke Slayton Cancer Center (2)
  • Utah
    • Murray, Utah, United States, 84157
      • Intermountain Medical Center Intermountain Healthcare
    • Ogden, Utah, United States, 84403
      • Northern Utah Cancer Associates Northern Utah Assoc (3)
    • Salt Lake City, Utah, United States, 84103
      • University of Utah / Huntsman Cancer Institute SC-2
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists Utah Cancer Specialists (11)
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists Fairfax Northern Virginia
    • Winchester, Virginia, United States, 22601
      • Shenandoah Oncology Shenandoah Oncology (5)
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties NW Medical Specialties

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patient has a confirmed diagnosis of a select solid tumor (except with a primary diagnosis of Urothelial cell carcinoma, Cholangiocarcinoma, Endometrial cancer, and Glioblastoma multiforme) or hematologic malignancies and is in need of treatment because of progression or relapse.

Patient's tumor has been evaluated and pre-identified as having a tumor with a FGFR genetic alteration. The qualifying alteration must be assessed and reported by a CLIA-certified laboratory.

Patient must have received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission.

Patient must have progressive and measurable disease per RECIST 1.1. or other appropriate hematological response criteria.

Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

Exclusion Criteria:

Patient has received prior treatment with BGJ398

Patients with Central Nervous System (CNS) metastasis or leptomeningeal carcinomatosis

Patient has received chemotherapy or other anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug.

Patients with acute or chronic pancreatitis

Patients with impaired cardiac function or clinically significant cardiac diseases

History and/or current evidence of extensive tissue calcification

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

Current evidence of corneal or retinal disorder/keratopathy

History and/or current evidence of renal or endocrine alterations of calcium/phosphate homeostasis

Patients with another primary malignancy within 3 years prior to starting study treatment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BGJ398; BGJ398 was dosed on a flat scale of 125 mg (e.g., 1 x 100 mg and 1 x 25 mg capsules) once daily for the first 21 days of the 28-day cycle (3 weeks on, 1 week off in a cycle). A complete treatment cycle is defined as 28 days.	Drug: BGJ398; BGJ398 was dosed on a flat scale of 125 mg (e.g., 1 x 100 mg and 1 x 25 mg capsules) once daily for the first 21 days of the 28-day cycle (3 weeks on, 1 week off in a cycle). A complete treatment cycle is defined as 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate (CBR) Associated With BGJ398 Treatment	Tumor Response: Overall response rate (ORR) and clinical benefit rate (CBR) for solid tumor (non-lymphoma) which excludes 3 TIO and 1 Lymphoma patients (hence 80 patients and not 84) Clinical benefit rate for patients with solid tumors were assessed using RECIST 1.1 and include responses of CR or PR or SD. For hematologic tumors other appropriate hematological response criteria may apply Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response (OR) or Partial Response (PR) or Greater	The key secondary endpoint, OR, was determined by Investigator assessment for each tumor assessment and defined as responses of CR and PR per RECIST version 1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR	baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months
Progression-Free Survival (PFS)	Kaplan-Meier estimates of PFS timing, months Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause	every 8 weeks until death, assessed up to 24 months
Kaplan-Meier Estimates of PFS Rate, % (95% CI)		Months 1, 2, 3, 4, 5, 6, 12, 18, 24
Overall Survival (OS)	Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause	every 8 weeks until death, assessed up to 36 months
Kaplan-Meier Estimates of Survival Rate, % (95% CI)	Overall survival (OS) is the time from the date of start of treatment to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last contact.	months 3, 6, 9, 12, 24
Number of Participants With 99 Day Minimum Duration of Response (DOR)	The duration of response (PR or greater) applies only to patients whose best response was PR or greater. It is defined as the Ttime from the first documented response to the date first documented disease progression or relapse or death due to any cause	baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2014
• Primary Completion (Actual): April 30, 2018
• Study Completion (Actual): April 30, 2018

Study Registration Dates

• First Submitted: June 6, 2014
• First Submitted That Met QC Criteria: June 9, 2014
• First Posted (Estimate): June 10, 2014

Study Record Updates

• Last Update Posted (Actual): June 18, 2019
• Last Update Submitted That Met QC Criteria: May 28, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: mutation; hematologic malignancy; FGFR; Solid tumor malignancy; translocations; signature; BGJ398; ligand; amplifications,; fusions
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Antineoplastic Agents; Infigratinib
• Other Study ID Numbers: CBGJ398XUS04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No