Locally Advanced or Metastatic Renal Cell Carcinoma MedDRA version: 20.0 Level: PT Classification code 10050513 Term: Metastatic renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10067946 Term: Renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Abexinostat
Product Code: PCI-24781
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ABEXINOSTAT
CAS Number: 1622385-42-5
Current Sponsor code: PCI-24781
Other descriptive na
Sponsors
Xynomic Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be enrolled in the study, patients will be required to meet all of the following criteria: 1. Patients aged >= 18 years at time of study entry. 2. Has histologically confirmed RCC with clear cell component. 3. Locally advanced and unresectable or metastatic disease. 4. Measurable disease as assessed only by the investigator (not verified by IRC) according to RECIST version 1.1. 5. Patients must not have had any prior VEGF tyrosine kinase inhibitor treatment in either (neo)adjuvant or locally advanced/metastatic setting. Up to 1 line of prior cytokine or immune checkpoint inhibitor treatment is allowed in either the (neo)adjuvant or metastatic setting provided screening scans indicate progressive disease (PD) during or following completion of treatment. 6. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 17.1). 7. Has adequate baseline organ function, as demonstrated by the following: • Serum creatinine 50 mL/min • Serum bilirubin =1.5 × 10^9/L • Hemoglobin>=8.0 g/dL • Platelet count >=100 × 10^9/L 9. Has provided signed informed consent before initiation of any study-specific procedures or treatment. 10. Must agree to, and be capable of, adhering to the study visit schedule and other protocol requirements, including follow-up for OS. 11. Patient must be at least 2 weeks from last systemic treatment or dose of radiation prior to date of randomization. 12. A female patient is eligible to enter and participate in this study if she is of: a. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female patient who: i. Has had a hysterectomy ii. Has had a bilateral oophorectomy (ovariectomy) iii. Has had a bilateral tubal ligation iv. Is postmenopausal b. Childbearing potential, including any female patient who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception. Acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows: • Complete abstinence from sexual intercourse for 14 days before exposure to investigational product (IP), through the dosing period, and for at least 21 days after the last dose of IP • Oral contraceptive, either combined or progestogen alone • Injectable progestogen • Estrogenic vaginal ring • Percutaneous contraceptive patches • Intrauterine device or intrauterine system with a documented failure rate of less than 1% per year • Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female patient's entry into the study, and this male patient is the sole partner for that patient • Double barrier met
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria at Screening will not be enrolled in the study: 1. Has persistent clinically significant toxicities (Grade >= 2; per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5) (NCI CTCAE) from previous anticancer therapy (excluding alopecia which is permitted and excluding Grades 2 and 3 laboratory abnormalities if they are not associated with symptoms, are not considered clinically significant by the investigator, and can be managed with available medical therapies). 2. Has untreated central nervous system (CNS) metastases. Patients with treated CNS metastases are eligible provided imaging demonstrates no new or progressive metastases obtained at least 4 weeks following completion of treatment. CNS imaging during Screening is not required unless clinically indicated. 3. Has had a major surgical procedure 28 days prior to study randomization. 4. Active uncontrolled bleeding or bleeding diathesis. 5. Clinically significant gastrointestinal abnormalities that may affect absorption of study medications or increase risk of bleeding or perforation, including: • Active peptic ulcer disease • Known intraluminal metastatic lesion(s) at high risk of bleeding or perforation • Active inflammatory bowel disease • History of intra-abdominal fistula or abscess within 28 days prior to randomization • Clinically significant gastrointestinal tract bleeding within 28 days prior to randomization • Any prior history of gastrointestinal tract perforation 6. Has an additional malignancy requiring treatment within the past 3 years. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ, and non-muscle invasive urothelial carcinoma. 7. Poorly controlled hypertension, defined as systolic blood pressure >= 160 or diastolic blood pressure >= 100 mmHg. Use of anti-hypertensives and rescreening is permitted. 8. History of any 1 or more of the following conditions within the past 6 months prior to randomization: a. Symptomatic peripheral vascular disease b. Coronary artery bypass graft surgery c. Myocardial infarction or unstable angina d. Cardiac angioplasty or stent placement e. Cerebrovascular accident including transient ischemic attack 9. A new pulmonary embolism or deep venous thrombosis diagnosed within 3 months prior to randomization. Patients on chronic stable anticoagulation for a pulmonary embolism and/or deep venous thrombosis diagnosed more than 3 months prior to date of randomization are eligible for study participation. 10. Has a QTcF interval > 480 msec. 11. New York Heart Association Class III or IV congestive heart failure. 12. Has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements. 13. Has known positive status for human immunodeficiency virus (HIV) active or chronic hepatitis B or hepatitis C (screening is not required). 14. Use of prohibited medication within 7 days or 5 half-lives, whichever is shorter, prior to first dose of study drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to compare the PFS between treatment arms per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded IRC.;Secondary Objective: The secondary objectives of the study are to: • Compared the PFS between treatment arms by investigator assessment. • Compare the OS between treatment arms. • Characterize the safety profile of pazopanib in combination with abexinostat. • Compare the ORR by RECIST version 1.1 between treatment arms. • Compare the DOR between treatment arms. • Describe the ORR and DOR in patients who cross over to receive pazopanib plus abexinostat at the time of disease progression on pazopanib monotherapy. • Assess the impact of pazopanib with or without abexinostat on disease-related symptoms and health-related Quality of Life (QoL).;Primary end point(s): Progression-free survival, defined as the time (month) interval between date of randomization and date of radiographic disease progression or death for those without prior evidence of progression, as assessed by blinded IRC according to RECIST version 1.1.;Timepoint(s) of evaluation of this end point: The time (month) interval between date of randomization and date of radiographic disease progression or death for those without prior evidence of progression. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Progression-free survival by investigator assessment according to RECIST version 1.1. • Overall survival, defined as the interval between date of randomization and date of death. • Adverse events by NCI CTCAE version 5. • Objective response rate as assessed by RECIST version 1.1 per the investigator and IRC. • Duration of response as assessed by RECIST version 1.1 per the investigator and IRC. • Objective response rate and DOR as assessed by RECIST version 1.1 in cross-over patient population per the investigator. • Mean change from Baseline in Functional Assessment of Cancer Therapy Kidney System Index (FKSI-19) and Functional Assessment of Chronic Illness Therapy (FACIT-F) scores. Exploratory Endpoints: • Change from Baseline in PBMC histone acetylation. • Baseline expression of HDAC2 and HDAC6 in PBMCs and association with clinical outcomes including PFS, ORR, and OS. • Change from Baseline in levels of blood biomarkers with clinical outcomes. • Tissue protein and RNA expression levels of VEGF, HDAC, and other potential biomarkers.;Timepoint(s) of evaluation of this end point: Progression-free survival by investigator assessment, Overall survival, defined as the interval between date of randomization and date of death. | — |
Countries
China, Czech Republic, France, Italy, Korea, Republic of, Poland, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Xynomic Pharmaceuticals, Inc.
Outcome results
None listed