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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 : July 29, 2020
Sponsor:
Information provided by (Responsible Party):
Elevar Therapeutics

Tracking Information
First Submitted Date  ICMJE September 24, 2019
First Posted Date  ICMJE October 8, 2019
Last Update Posted Date July 29, 2020
Actual Study Start Date  ICMJE March 4, 2020
Estimated Primary Completion Date February 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 7, 2019)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2020)
  • OS [ Time Frame: Up to 48 months ]
    Overall survival
  • DoR [ Time Frame: Up to 48 months ]
    Duration of Response (DoR) per RECIST Version 1.1 by investigator assessment
  • PFS [ Time Frame: PFS at 6 months, 12 months and 2 years per RECIST Version 1.1 by investigator assessment ]
    Progression free survival (PFS)
  • TTP [ Time Frame: Up to 48 months ]
    Time to progression (TTP) per RECIST Version 1.1 by investigator assessment
  • 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2019)
  • OS [ Time Frame: Up to 48 months ]
    Overall survival
  • DCR [ Time Frame: Up to 48 months ]
    Disease control rate (DCR) per RECIST Version 1.1 by investigator assessment
  • PFS [ Time Frame: PFS at 6 months, 12 months and 2 years per RECIST Version 1.1 by investigator assessment ]
    Progression free survival (PFS)
  • TTP [ Time Frame: Up to 48 months ]
    Time to progression (TTP) per RECIST Version 1.1 by investigator assessment
  • 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)
Current Other Pre-specified Outcome Measures
 (submitted: July 26, 2020)
  • 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
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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.
  • Evaluate Disease control rate (DCR) of rivoceranib [ Time Frame: Up to 48 months ]
    DCR per RECIST Version 1.1 by Investigator assessment
Original Other Pre-specified Outcome Measures
 (submitted: October 7, 2019)
  • 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
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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.
 
Descriptive Information
Brief Title  ICMJE Phase 2 Study to Evaluate the Efficacy and Safety of Rivoceranib in Subjects With Recurrent or Metastatic ACC
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE ACC
Intervention  ICMJE Drug: Rivoceranib
Rivoceranib will be supplied as 100 mg and 200 mg film-coated tablets for oral (PO) administration
Other Name: Rivoceranib Mesylate
Study Arms  ICMJE 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.
Intervention: Drug: Rivoceranib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 26, 2020)
72
Original Estimated Enrollment  ICMJE
 (submitted: October 7, 2019)
55
Estimated Study Completion Date  ICMJE February 1, 2024
Estimated Primary Completion Date February 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Patients are eligible if CNS metastases have been treated and patients are neurologically returned to baseline or neurologically stable in the opinion of Investigator (except for residual signs or symptoms related to the CNS treatment) for at least 4 weeks prior to first dose of study drug administration. In addition, patients must be either off corticosteroids, or on a stable dose or decreasing dose of <20 mg daily prednisone or prednisone equivalent.

    Note: Only subjects with a known history or indication of CNS disease are required to have CNS imaging prior to study entry

  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), prothrombin time (PT) 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 1) 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 based on Investigator's clinical judgement (consistent blood pressure readings ≥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 5 half-lives prior to first dose of study drug
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Steven Norton, PhD 8013037440 ext 275 steven.norton@elevartherapeutics.com
Listed Location Countries  ICMJE Korea, Republic of,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04119453
Other Study ID Numbers  ICMJE RM-202
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Elevar Therapeutics
Study Sponsor  ICMJE Elevar Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Steven Norton, PhD Elevar Therapeutics,inc
PRS Account Elevar Therapeutics
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP