| Eligibility |
Inclusion Criteria:
1. Histologically or cytologically confirmed metastatic/recurrent ACC not amenable to
potentially curative surgery or radiotherapy
2. Evidence of disease progression by RECIST v1.1
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. Participants are eligible if central nervous system (CNS) metastases have been treated
and participants 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, participants must be either off corticosteroids, or on a stable dose or
decreasing dose of <20 milligrams (mg) daily prednisone or prednisone equivalent.
Note: Only participants 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/microliters (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 milliliters (mL)/minute (min)
(Cockcroft-Gault)
6. Partial thromboplastin time (PTT), prothrombin time (PT) and international
normalized ratio (INR) =1.5×ULN
7. Hemoglobin =9.0 grams (g)/deciliter (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.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. The ability to understand and the willingness to sign a written informed consent
9. Female participants who are of non-reproductive potential (that is, 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 participants of
childbearing potential must have a negative serum pregnancy test within 72 hours prior
to the first dose of rivoceranib.
10. Male and female participants of reproductive potential who agree to use both a highly
effective method of birth control (for example, implants, injectables, combined oral
contraceptives, some intrauterine devices, complete abstinence, or sterilized partner)
and a barrier method (for example condoms, cervical ring, sponge, etc.) during the
period of therapy and for 30 days after the final dose of rivoceranib. Female
participants should also refrain from breastfeeding and egg donation and males should
refrain from sperm donation throughout this period
11. QTc interval <480 milliseconds (ms) (Common Terminology Criteria for Adverse Events
[CTCAE] Grade 1) using Fredericia's QT correction formula
Exclusion Criteria:
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 participant 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. Participants 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 millimeters of mercury [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 (for example, ramucirumab) that may indicate a
higher risk to the safety of the participant 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 (for example, 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 participant 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 participant 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 participant's safety or
study endpoints
17. A female participant 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) participant with
an undetectable surface antigen and negative hepatitis B deoxyribonucleic acid (DNA)
test (for example, polymerase chain reaction [PCR] test) can be enrolled.
22. Known seropositive requiring antiviral therapy for hepatitis C virus (HCV) infection
OR participants with positive hepatitis C virus antibody NOTE: A positive Anti-HCV
participant with an undetectable/negative hepatitis C ribonucleic acid (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. Participants unable or unwilling to discontinue excluded medications for at least 5
half-lives prior to first dose of study drug
|
