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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)

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ClinicalTrials.gov Identifier: NCT04595747
Recruitment Status : Recruiting
First Posted : October 22, 2020
Last Update Posted : August 16, 2021
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Gastrointestinal Stromal Tumor Recurrent Sarcoma Drug: Rogaratinib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 1, 2021
Estimated Primary Completion Date : February 5, 2023
Estimated Study Completion Date : February 5, 2023


Arm Intervention/treatment
Experimental: Treatment (rogaratinib)
Patients 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.
Drug: Rogaratinib
Given PO
Other Names:
  • BAY-1163877
  • BAY1163877




Primary Outcome Measures :
  1. Objective radiographic response [ Time Frame: Up to 30 days after removal from study ]
    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 :
  1. 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 ]
    Will be estimated using Kaplan-Meier method.

  2. Overall survival [ Time Frame: Up to 30 days after removal from study ]
    Will be estimated using Kaplan-Meier method.

  3. Incidence of adverse events [ Time Frame: Up to 30 days after removal from study ]
    Adverse events will be measured by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.


Other Outcome Measures:
  1. Serial measurements of FGFR and FGFR ligand [ Time Frame: Up to 30 days after removal from study ]
    Will be evaluated in serial tumor biopsies as potential pharmacodynamic markers of FGFR pathway inhibition by ribonucleic acid sequencing. Estimation of continuous biomarker measures will be via mean or median as appropriate and standard deviation.

  2. Mechanisms of resistance [ Time Frame: Up to 30 days after removal from study ]
    Will identify mechanisms of resistance via whole exome sequencing of pre- and post-treatment biopsies and considered exploratory.

  3. Banking of tumor material, germline deoxyribonucleic acid, and peripheral blood [ Time Frame: Up to 30 days after removal from study ]
    Will be banked for potential research.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04595747


Locations
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United States, California
City of Hope Comprehensive Cancer Center Recruiting
Duarte, California, United States, 91010
Contact: Site Public Contact    800-826-4673    becomingapatient@coh.org   
Principal Investigator: Mark Agulnik         
United States, Maryland
National Cancer Institute Developmental Therapeutics Clinic Recruiting
Bethesda, Maryland, United States, 20892
Contact: Site Public Contact    800-411-1222      
Principal Investigator: A P. Chen         
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: Site Public Contact    800-411-1222      
Principal Investigator: A P. Chen         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Site Public Contact    877-442-3324      
Principal Investigator: Suzanne George         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Site Public Contact    212-639-7592      
Principal Investigator: Katherine A. Thornton         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Suzanne George Dana-Farber - Harvard Cancer Center LAO
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04595747    
Other Study ID Numbers: NCI-2020-08011
NCI-2020-08011 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
10411 ( Other Identifier: Dana-Farber - Harvard Cancer Center LAO )
10411 ( Other Identifier: CTEP )
UM1CA186709 ( U.S. NIH Grant/Contract )
First Posted: October 22, 2020    Key Record Dates
Last Update Posted: August 16, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
URL: https://grants.nih.gov/policy/sharing.htm

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Sarcoma
Gastrointestinal Stromal Tumors
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Connective Tissue
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases