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Trial record 1 of 6 for:    rivoceranib
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Phase 2 Study to Evaluate the Efficacy and Safety of Rivoceranib in Subjects With Recurrent or Metastatic ACC

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ClinicalTrials.gov Identifier: NCT04119453
Recruitment Status : Recruiting
First Posted : October 8, 2019
Last Update Posted : June 23, 2020
Sponsor:
Information provided by (Responsible Party):
Elevar Therapeutics

Brief Summary:
This is a Phase 2, multicenter, open-label, single-arm study of rivoceranib to evaluate its efficacy and safety in adult subjects with metastatic ACC of all anatomic sites of origin.

Condition or disease Intervention/treatment Phase
ACC Drug: Rivoceranib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 55 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Rivoceranib will be supplied as 100 mg and 200 mg film-coated tablets for oral (PO) administration.

Subjects will be treated with oral rivoceranib, 700 mg daily during 28-day cycles. Subjects will be monitored for clinical and/or radiographic evidence of disease progression as assessed by tumor growth or the discovery of additional tumors. Restaging scans will be performed approximately every 8 weeks for the first year and then approximately every 12 weeks and at End of Treatment (EOT), or as clinically indicated. Subjects who discontinue treatment for reasons other than progression will have scans at the EOT visit (unless their previous restaging was performed within 6 weeks) and approximately every 12 weeks thereafter (or with the standard of care restaging frequency for their disease) until initiation of a new therapy.

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Open-Label, Multicenter, Study to Evaluate the Efficacy and Safety of Rivoceranib in Subjects With Recurrent or Metastatic Adenoid Cystic Carcinoma (ACC) of All Anatomic Sites of Origin
Actual Study Start Date : March 4, 2020
Estimated Primary Completion Date : February 1, 2022
Estimated Study Completion Date : February 1, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Adenoids

Arm Intervention/treatment
Experimental: Oral rivoceranib, 700 mg daily during 28-day cycles
Subjects will be treated with oral rivoceranib, 700 mg daily during 28-day cycles. Subjects will be monitored for clinical and/or radiographic evidence of disease progression as assessed by tumor growth or the discovery of additional tumors. Restaging scans will be performed approximately every 8 weeks for the first year and then approximately every 12 weeks and at End of Treatment (EOT), or as clinically indicated. Subjects who discontinue treatment for reasons other than progression will have scans at the EOT visit (unless their previous restaging was performed within 6 weeks) and approximately every 12 weeks thereafter (or with the standard of care restaging frequency for their disease) until initiation of a new therapy.
Drug: Rivoceranib
Rivoceranib will be supplied as 100 mg and 200 mg film-coated tablets for oral (PO) administration
Other Name: Rivoceranib Mesylate




Primary Outcome Measures :
  1. Evaluate efficacy of rivoceranib in subjects with recurrent or metastatic Adenoid Cystic Carcinoma (ACC) based on assessment of ORR [ Time Frame: Up to 48 months ]
    ORR per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by investigator assessment.


Secondary Outcome Measures :
  1. OS [ Time Frame: Up to 48 months ]
    Overall survival

  2. DCR [ Time Frame: Up to 48 months ]
    Disease control rate (DCR) per RECIST Version 1.1 by investigator assessment

  3. PFS [ Time Frame: PFS at 6 months, 12 months and 2 years per RECIST Version 1.1 by investigator assessment ]
    Progression free survival (PFS)

  4. TTP [ Time Frame: Up to 48 months ]
    Time to progression (TTP) per RECIST Version 1.1 by investigator assessment

  5. Evaluate safety of rivoceranib [ Time Frame: Screening through 30 calendar days after stopping of treatment or until initiation of new,non-protocol specified systemic anticancer therapy, whichever occurs first, assessed up to approximately 48 months ]
    Safety assessments (e.g., new adverse events (AEs), AEs present at baseline that worsen in severity during the study, and clinical laboratory abnormalities)


Other Outcome Measures:
  1. Explore pharmacodynamic markers; Archival tumor tissue, if available or fresh tumor samples will be collected to investigate presence of MYB or MYB-L1 translocations. [ Time Frame: Day 1 ]
    Correlate presence of MYB or MYB-L1 translocations with response to rivoceranib

  2. Evaluate the pharmacokinetics (PK) of rivoceranib: Cmax [ Time Frame: Every 28 days from Day 1 of each cycle up to End of Treatment, assessed up to approximately 24 months after last patient enrolled ]
    Maximum observed serum concentration (Cmax)

  3. Evaluate the pharmacokinetics (PK) of rivoceranib: Tmax [ Time Frame: Every 28 days from Day 1 of each cycle up to End of Treatment, assessed up to approximately 24 months after last patient enrolled ]
    Time of peak concentration (Tmax)

  4. Evaluate the pharmacokinetics (PK) of rivoceranib: AUC [ Time Frame: Every 28 days from Day 1 of each cycle up to End of Treatment, assessed up to approximately 24 months after last patient enrolled ]
    Time of peak concentration (Tmax)

  5. Evaluate the pharmacokinetics (PK) of rivoceranib: CL [ Time Frame: Every 28 days from Day 1 of each cycle up to End of Treatment, assessed up to approximately 24 months after last patient enrolled ]
    Clearance (CL)

  6. Evaluate the pharmacokinetics (PK) of rivoceranib: t1/2 [ Time Frame: Every 28 days from Day 1 of each cycle up to End of Treatment, assessed up to approximately 24 months after last patient enrolled ]
    Terminal elimination half-life (t1/2)

  7. Evaluate quality of life measurements during treatment with rivoceranib [ Time Frame: Subjects will complete (FACT)-G questionnaire every 8 weeks for the first year of therapy, then every 12 weeks thereafter and at End of Treatment (EOT), assessed up to approximately 24 months after last patient enro ]
    Patient reported outcomes will be assessed using the Functional Assessment of Cancer Therapy (FACT)-G questionnaire. The scores from these questionnaires will be summarized by study visit using descriptive statistics.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Subjects are eligible to be included in the study only if all the following criteria apply:

Disease Related

  1. Histologically or cytologically confirmed metastatic/recurrent ACC not amenable to potentially curative surgery or radiotherapy
  2. Evidence of disease progression Note: Disease progression is defined as one of the following occurring within the 6 months prior to study entry:

    1. At least a 20% increase in radiologically or clinically measurable lesions
    2. Appearance of any new lesions
  3. Presence of at least one measurable target lesion which is evaluable by RECIST v1.1 criteria
  4. Subjects with history of central nervous system (CNS) metastases are eligible if CNS disease has been stable, in the opinion of the investigator, for at least 4 weeks prior to study enrollment. Stable doses of corticosteroids (not to exceed 20 mg of prednisone) for symptomatic management are allowed Note: Only subjects with a known history or indication of CNS disease are required to have CNS imaging prior to study entry Laboratory
  5. Adequate organ and marrow function within 14 days prior to the first dose of rivoceranib administration, defined as:

    1. Absolute neutrophil count ≥1500/μL
    2. Platelet count ≥100,000/μL
    3. Serum bilirubin ≤1.5× upper limit of normal (ULN)
    4. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0×ULN (≤5.0×ULN, if with liver metastasis)
    5. Estimated Creatinine Clearance >50 mL/min (Cockcroft-Gault)
    6. Partial thromboplastin time (PTT) and international normalized ratio (INR) ≤1.5×ULN
    7. Hemoglobin ≥9.0 g/dL
  6. Urinary protein <2+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥2+, a 24-hour urine or urine protein/creatinine ratio must be collected and must demonstrate <2 g of protein in 24 hours Demographic
  7. Men and women ≥18 years of age (or age of majority, if higher per local regulations)
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Ethical/Other
  9. The ability to understand and the willingness to sign a written informed consent
  10. Female subjects who are of non-reproductive potential (i.e. post-menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to the first dose of rivoceranib
  11. Male and female subjects of reproductive potential who agree to use both a highly effective method of birth control (e.g. implants, injectables, combined oral contraceptives, some intrauterine devices, complete abstinence, or sterilized partner) and a barrier method (e.g. condoms, cervical ring, sponge, etc.) during the period of therapy and for 30 days after the final dose of rivoceranib. Female subjects should also refrain from breastfeeding and egg donation and males should refrain from sperm donation throughout this period
  12. QTc interval > 480 milliseconds (ms) (CTCAE grade 2) using Fredericia's QT correction formula

Exclusion Criteria:

  • Subjects will be excluded from the study if any of the following criteria apply:

Disease Related

  1. Previous treatment with rivoceranib
  2. Known hypersensitivity to rivoceranib or components of the formulation
  3. Packed red blood cell transfusion or erythropoietin therapy within 14 days prior to the first dose of rivoceranib administration
  4. History of another malignancy within 3 years prior to enrollment. A subject with the following malignancies is eligible for this study if, surgically and medically treated and in the opinion of the investigator, they do not pose a significant risk to life expectancy or not likely to recur within 3 years:

    1. Carcinoma of the skin without melanomatous features
    2. Curatively treated cervical carcinoma in situ
    3. Bladder tumors considered superficial such as noninvasive (T1a) and carcinoma in situ (Tis)
    4. Thyroid papillary cancer with prior treatment
    5. Prostate cancer which has been surgically or medically treated
  5. Prior chemotherapy, radiation therapy or major surgery within 4 weeks prior to rivoceranib administration or presence of any nonhealing wound (procedures such as catheter placement are not considered to be major surgery). Prior immunotherapy within 12 weeks prior to first dose of study drug. Palliative radiotherapy to non-target lesions within 2 weeks prior to rivoceranib administration or biopsy any time prior to rivoceranib administration is permitted
  6. Prior tyrosine kinase inhibitor therapy targeting vascular endothelial growth factor receptors (VEGFR), within 5 half-lives prior to rivoceranib administration
  7. Subjects who have not recovered to ≤ Grade 1 from prior tyrosine kinase inhibitor-related adverse events
  8. History of uncontrolled hypertension (blood pressure ≥140/90 mmHg and/or change in antihypertensive medication within 7 days prior to rivoceranib administration)
  9. History of severe adverse events including uncontrolled hypertension or other common anti-angiogenesis class drug effects (e.g. ramucirumab) that may indicate a higher risk to the safety of the subject if provided further anti-angiogenesis treatment, in the investigator's opinion
  10. History of vascular disease including arterial or venous embolic events (pulmonary embolism), other than hypertension, within the last 3 months prior to treatment with rivoceranib (e.g. hypertensive crisis, hypertensive encephalopathy, stroke or transient ischemic attack [TIA], or significant peripheral vascular diseases) that, in the investigator's opinion, may pose a risk to the subject on vascular endothelial growth factor (VEGF) inhibitor therapy
  11. History of bleeding diathesis or clinically significant bleeding within 14 days prior to treatment with rivoceranib
  12. History of clinically significant thrombosis within 3 months prior to treatment with rivoceranib that, in the investigator's opinion, may place the subject at risk of side effects from anti-angiogenesis products
  13. Therapy with systemic anticoagulant or antithrombotic agents within 7 days prior to treatment with rivoceranib that in the investigator's opinion could interfere with clotting. The maximum allowable daily dose of aspirin is 325 mg
  14. Gastrointestinal malabsorption, or any other condition that in the opinion of the investigator might affect the absorption of rivoceranib
  15. History of clinically significant glomerulonephritis, biopsy-proven tubulointerstitial nephritis, crystal nephropathy, or other renal insufficiencies
  16. An uncontrolled intercurrent illness including, but not limited to any of the following:

    1. Ongoing or active infection (including minor localized infections) requiring oral or intravenous treatment
    2. Symptomatic class 3 or 4 congestive heart failure, defined as a clinical syndrome resulting from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood
    3. Unstable angina pectoris
    4. Cardiac arrhythmia
    5. Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the subject's safety or study endpoints Ethical/Other
  17. A female subject who is pregnant or breast-feeding
  18. Psychiatric illness/social situations that would limit compliance with study requirements
  19. History of drug or alcohol abuse within the past 5 years
  20. Known seropositive requiring anti-viral therapy for human immunodeficiency virus (HIV) infection
  21. Known seropositive requiring antiviral therapy for hepatitis B virus (HBV) infection OR evidence of active hepatitis B infection by detectable viral load if the antibody tests are positive NOTE: A positive hepatitis B core antibody (HBcAb) subject with an undetectable surface antigen and negative hepatitis B DNA test (e.g., polymerase chain reaction [PCR] test) can be enrolled
  22. Known seropositive requiring antiviral therapy for hepatitis C virus (HCV) infection OR subjects with positive hepatitis C virus antibody NOTE: A positive Anti-HCV subject with an undetectable/negative hepatitis C RNA test can be enrolled
  23. Participation in another clinical study with any investigational medication or product administered within ≤28 days prior to first dose of rivoceranib
  24. Subjects unable or unwilling to discontinue excluded medications for at least 2 weeks prior to first dose of rivoceranib

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): NCT04119453


Contacts
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Contact: Steven Norton, PhD 8013037440 ext 275 steven.norton@elevartherapeutics.com

Locations
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United States, California
University of California, Los Angeles (UCLA) Recruiting
Los Angeles, California, United States, 90095
Contact: Elizabeth Seja         
Principal Investigator: Deborah Wong, MD         
UCSF Recruiting
San Francisco, California, United States, 94143
Contact: PI         
Principal Investigator: Kang, MD         
United States, Colorado
University of Colorado Denver Recruiting
Denver, Colorado, United States, 80204
Contact: Rina Villar         
Principal Investigator: Daniel Bowles, MD         
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Ianni Gue         
Principal Investigator: Jameel Muzaffar, MD         
United States, Illinois
University of Chicago Not yet recruiting
Chicago, Illinois, United States, 60637
Contact: Pearson, MD         
Principal Investigator: Pearson, MD         
United States, Massachusetts
Dana-Farber Cancer Institute - Head and Neck Oncology Recruiting
Boston, Massachusetts, United States, 02215
Contact: Evan carey         
Principal Investigator: Glen Hanna, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Francis Worden         
Principal Investigator: Francis Worden, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
Principal Investigator: Alan Ho, MD         
Korea, Republic of
National Cancer Center Recruiting
Goyang-si, Gyeonggi-do, Korea, Republic of
Contact: Tak, MD         
Principal Investigator: Tak Yun         
Seoul National University Hospital Recruiting
Seoul, Gyeonggi-do, Korea, Republic of
Principal Investigator: BhumSuk Keam         
Asan Medical Center Recruiting
Seoul, Gyeonggi, Korea, Republic of
Principal Investigator: Sung-Bae Kim, MD         
Samsung Medical Center Recruiting
Seoul, Korea, Republic of
Principal Investigator: Myung-Ju Anh, MD         
Sponsors and Collaborators
Elevar Therapeutics
Investigators
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Study Director: Steven Norton, PhD Elevar Therapeutics,inc
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Responsible Party: Elevar Therapeutics
ClinicalTrials.gov Identifier: NCT04119453    
Other Study ID Numbers: RM-202
First Posted: October 8, 2019    Key Record Dates
Last Update Posted: June 23, 2020
Last Verified: June 2020

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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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Apatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action