Clinical Trials /

Testing the Anti-cancer Drug, Rogaratinib (BAY 1163877), for Treatment of Advanced Sarcoma With Alteration in Fibroblast Growth Factor Receptor (FGFR 1-4), and in Patients With SDH-deficient Gastrointestinal Stromal Tumor (GIST)

NCT04595747

Description:

This phase II trial studies the effect of rogaratinib in treating patients with sarcoma with a change in a group of proteins called fibroblast growth factor receptors (FGFRs) or SDH-deficient gastrointestinal stromal tumor (GIST). Rogaratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Gastrointestinal Stromal Tumor
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Testing the Anti-cancer Drug, Rogaratinib (BAY 1163877), for Treatment of Advanced Sarcoma With Alteration in Fibroblast Growth Factor Receptor (FGFR 1-4), and in Patients With SDH-deficient Gastrointestinal Stromal Tumor (GIST)
  • Official Title: Phase 2 Study of Rogaratinib (BAY 1163877) in the Treatment of Patients With Sarcoma Harboring Alterations in Fibroblast Growth Factor Receptor (FGFR) 1-4 and SDH-Deficient Gastrointestinal Stromal Tumor (GIST)

Clinical Trial IDs

  • ORG STUDY ID: NCI-2020-08011
  • SECONDARY ID: NCI-2020-08011
  • SECONDARY ID: 10411
  • SECONDARY ID: 10411
  • SECONDARY ID: UM1CA186709
  • NCT ID: NCT04595747

Conditions

  • Gastrointestinal Stromal Tumor
  • Recurrent Sarcoma

Interventions

DrugSynonymsArms
RogaratinibBAY-1163877, BAY1163877Treatment (rogaratinib)

Purpose

This phase II trial studies the effect of rogaratinib in treating patients with sarcoma with a change in a group of proteins called fibroblast growth factor receptors (FGFRs) or SDH-deficient gastrointestinal stromal tumor (GIST). Rogaratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To estimate the objective radiographic response rate to single agent rogaratinib (BAY
      1163877) in two cohorts of patients with sarcoma: Cohort A defined as patients with a sarcoma
      which harbors an alteration in fibroblast growth factor receptor (FGFR) 1, 2, 3 or 4
      identified by next-generation sequencing profiling, and Cohort B defined as patients with
      advanced succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST).

      SECONDARY OBJECTIVES:

      I. To estimate progression-free survival (PFS) and overall survival (OS) in patients in
      Cohort A and Cohort B treated with rogaratinib (BAY 1163877).

      II. Further assessment for safety and tolerability.

      EXPLORATORY OBJECTIVES:

      I. To evaluate serial measurements of FGFR and FGFR ligand in serial tumor biopsies as
      potential pharmacodynamic markers of FGFR pathway inhibition by ribonucleic acid sequencing
      (RNA-seq) (pre-treatment biopsy and post-progression biopsy).

      II. Whole exome sequencing (WES) of the pre and post treatment biopsy to help identify
      mechanisms of resistance.

      III. To bank tumor material, germline deoxyribonucleic acid (DNA), and peripheral blood for
      potential future research for participating subjects who provide additional consent.

      OUTLINE:

      Patients receive rogaratinib orally (PO) twice daily (BID) on days 1-28. Treatment repeats
      every 28 days for up to 24 cycles in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up at 30 days.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (rogaratinib)ExperimentalPatients receive rogaratinib PO BID on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
  • Rogaratinib

Eligibility Criteria

        Inclusion Criteria:

          -  Participant must have histologically confirmed sarcoma with FGFR alteration identified
             by next-generation sequencing profiling with the exception of SDH-deficient GIST who
             can be enrolled regardless of FGFR status. Initial testing can be performed on
             archival tissue

          -  Presence of measurable disease: Patient must have measurable disease

          -  Patients must have progressed following at least one standard prior chemotherapy
             regimen with the exception of SDH-deficient GIST for which there is no standard of
             care

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

          -  Hemoglobin >= 8.0 g/dL

          -  Absolute neutrophil count >= 1,000/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =<
             3.0 x institutional ULN (unless liver metastases are present in which case it must be
             =< 5 x ULN)

          -  Creatinine =< 1.5 x institutional ULN OR glomerular filtration rate (GFR) >= 60
             mL/min/1.73 m^2

          -  Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
             therapy with undetectable viral load within 6 months are eligible for this trial

          -  For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
             load must be undetectable on suppressive therapy, if indicated

          -  Patients with a history of hepatitis C virus (HCV) infection must have been treated
             and cured. For patients with HCV infection who are currently on treatment, they are
             eligible if they have an undetectable HCV viral load

          -  Patients with treated brain metastases are eligible if follow-up brain imaging after
             central nervous system (CNS)-directed therapy shows no evidence of progression

          -  Patients must be disease-free of prior invasive malignancies for > 5 years with the
             exception of curatively-treated basal cell or squamous cell carcinoma of the skin or
             carcinoma in situ of the cervix

               -  NOTE: If there is a history of prior malignancy, patients must not be receiving
                  other specific treatment for that cancer

          -  Patients should have completed prior treatment for their cancer: chemotherapy or
             radiotherapy must have been completed for greater than 2 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study

          -  Patients should have recovered from adverse events due to prior anti-cancer therapy
             (i.e., have residual toxicities > grade 1) with the exception of alopecia

          -  Patients with known history or current symptoms of cardiac disease, or history of
             treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
             function using the New York Heart Association functional classification. To be
             eligible for this trial, patients should be class 2B or better

          -  Participant is willing to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations including follow
             up

          -  Participant must be able to swallow and maintain pills

          -  Women of childbearing potential must have a negative urine or serum pregnancy test
             within 28 days of initial dose of rogaratinib (BAY 1163877), and again within 7 days
             prior to treatment on day 1. If screening occurs within 7 days of day 1, only one
             pregnancy test is required. Postmenopausal is defined as:

               -  Amenorrhoeic for 1 year or more following cessation of exogenous hormonal
                  treatments

               -  Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the
                  post-menopausal range for women under 50

               -  Radiation-induced oophorectomy with last menses > 1 year ago

               -  Chemotherapy-induced menopause with > 1-year interval since last menses, or
                  surgical sterilization (bilateral oophorectomy or hysterectomy)

          -  The effects of rogaratinib (BAY 1163877) on the developing human fetus are unknown.
             For this reason and because kinase inhibitor agents are known to be teratogenic, women
             of child-bearing potential and men must agree to use adequate contraception (hormonal
             or barrier method of birth control; abstinence) prior to study entry, for the duration
             of study participation, and 4 months after completion of rogaratinib (BAY 1163877).
             Should a woman become pregnant or suspect she is pregnant while she or her partner is
             participating in this study, she should inform her treating physician immediately. Men
             treated or enrolled on this protocol must also agree to use adequate contraception
             prior to the study, for the duration of study participation, and 4 months after
             completion of rogaratinib (BAY 1163877) administration

          -  Ability to understand and the willingness to sign a written informed consent document.
             Participants with impaired decision-making capacity (IDMC) who have a
             legally-authorized representative (LAR) and/or family member available will also be
             eligible

        Exclusion Criteria:

          -  Patients who are receiving any other investigational agents

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to rogaratinib (BAY 1163877)

          -  Concomitant administration with sensitive substrates/narrow therapeutic index drugs of
             CYP3A4, P-gp BCRP, MATE1, and MATE2K, and strong inhibitors and inducers of CYP3A4
             should be avoided. Use caution with strong inhibitors and inducers of P-glycoprotein
             (gp). Because the lists of these agents are constantly changing, it is important to
             regularly consult a frequently-updated medical reference. As part of the
             enrollment/informed consent procedures, the patient will be counseled on the risk of
             interactions with other agents, and what to do if new medications need to be
             prescribed or if the patient is considering a new over-the-counter medicine or herbal
             product

          -  Patients with uncontrolled intercurrent illness

          -  Patients with psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women are excluded from this study because rogaratinib (BAY 1163877) is
             kinase inhibitor agent with the potential for teratogenic or abortifacient effects.
             Because there is an unknown but potential risk for adverse events in nursing infants
             secondary to treatment of the mother with rogaratinib (BAY 1163877), breastfeeding
             should be discontinued if the mother is treated with rogaratinib (BAY 1163877)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective radiographic response
Time Frame:Up to 30 days after removal from study
Safety Issue:
Description:The duration of overall response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:From start of treatment to time of progression or death, whichever occurs first, assessed up to 30 days after removal from study
Safety Issue:
Description:Will be estimated using Kaplan-Meier method.
Measure:Overall survival
Time Frame:Up to 30 days after removal from study
Safety Issue:
Description:Will be estimated using Kaplan-Meier method.
Measure:Incidence of adverse events
Time Frame:Up to 30 days after removal from study
Safety Issue:
Description:Adverse events will be measured by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

May 7, 2021