Clinical Trials /

Phase 2 Study to Evaluate the Efficacy and Safety of Rivoceranib in Subjects With Recurrent or Metastatic ACC

NCT04119453

Description:

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.

Related Conditions:
  • Adenoid Cystic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2 Study to Evaluate the Efficacy and Safety of Rivoceranib in Subjects With Recurrent or Metastatic ACC
  • 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

Clinical Trial IDs

  • ORG STUDY ID: RM-202
  • NCT ID: NCT04119453

Conditions

  • ACC

Interventions

DrugSynonymsArms
RivoceranibRivoceranib MesylateOral rivoceranib, 700 mg daily during 28-day cycles

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Oral rivoceranib, 700 mg daily during 28-day cyclesExperimentalSubjects 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.
  • Rivoceranib

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:ORR per the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by investigator assessment.

Secondary Outcome Measures

Measure:OS
Time Frame:Up to 48 months
Safety Issue:
Description:Overall survival
Measure:DCR
Time Frame:Up to 48 months
Safety Issue:
Description:Disease control rate (DCR) per RECIST Version 1.1 by investigator assessment
Measure:PFS
Time Frame:PFS at 6 months, 12 months and 2 years per RECIST Version 1.1 by investigator assessment
Safety Issue:
Description:Progression free survival (PFS)
Measure:TTP
Time Frame:Up to 48 months
Safety Issue:
Description:Time to progression (TTP) per RECIST Version 1.1 by investigator assessment
Measure: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 Issue:
Description:Safety assessments (e.g., new adverse events (AEs), AEs present at baseline that worsen in severity during the study, and clinical laboratory abnormalities)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Elevar Therapeutics

Last Updated

April 18, 2020