Study of the Pan-DAC Inhibitor AR-42 and Pazopanib in Advanced Sarcoma and Kidney Cancer

Stopped early · Phase 1

Conditions studied: Renal Cell Carcinoma, Soft Tissue Sarcoma, Metastatic Disease

In brief

This phase 1 study was developed to identify recommended phase 2 doses (RP2Ds) of AR-42 and pazopanib when given in combination for subsequent clinical trials and may have potentially identified candidate pharmacodynamic and predictive biomarkers.

Key facts

Study ID

NCT02795819

Run by

Virginia Commonwealth University

People needed

6

Starts

2016-07-08

Expected to finish

2019-03-14

Last updated by the study team

2019-10-24

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Recurrent, unresectable, or metastatic Renal Cell Carcinoma (RCC) or Soft Tissue Sarcoma (STS) (any histologic type) for which pazopanib was an appropriate therapy
• Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate bone marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1200/mm3
• Platelets ≥ 120,000/mm3
• Hemoglobin ≥ 9.5 g/dL
• Adequate renal function as defined below:
• Creatinine ≤ 1.5 x upper limit of normal (ULN) for the laboratory or calculated or actual creatinine clearance ≥ 60 mL/min
• Proteinuria ≤ 2+ [100 mg/dL] (using a random urine sample or < 3.0 gm using a 24-hour sample) (Note: If urine sample indicates ≥ 2+ [100 mg/dL]), a 24-hour urine sample must be collected and tested; urine protein in the 24-hour sample must be < 3.0 gm/24 hours.)
• Adequate hepatic function as defined below:
• Total bilirubin ≤ 1.5 x ULN for the laboratory (Note: Patients with known Gilbert's Syndrome were not eligible for this study)
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN for the laboratory
• Alanine aminotransferase (ALT) ≤ 2.5 x ULN for the laboratory
• Non-hematologic toxicities from previous cancer therapies resolved to ≤ grade 1
• International normalized ratio (INR) ≤ 1.5
• Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN for the laboratory
• Left ventricular ejection fraction (LVEF) assessment (eg, echocardiogram, MUGA scan, first-pass technique) performed within 3 months prior to initiation of study treatment indicates an LVEF of ≥ 50%
• A woman of childbearing potential (WCBP), defined as a woman who was < 60 years of age and had not had a hysterectomy, must have had a documented negative serum pregnancy test within 7 days prior to initiating study treatment
• A WCBP and a male patient with a partner who was a WCBP must have agreed to use a medically accepted method for preventing pregnancy for the duration of study treatment and for 2 months following completion of study treatment
• Ability to have understood and willingness to have signed the consent form

You may not qualify if…

• Symptomatic or untreated brain metastasis
• Leptomeningeal metastasis
• Any investigational agent within 4 weeks prior to initiating study treatment
• Previous therapy with pazopanib
• Inability to swallow medication
• Known or suspected malabsorption condition or obstruction
• Contraindication to antiangiogenic agents, including:
• Serious non-healing wound, non-healing ulcer, or bone fracture
• Major surgical procedure or significant traumatic injury within 4 weeks prior to initiating study treatment; other surgical procedures within 2 weeks prior to initiating study treatment
• Pulmonary hemorrhage/bleeding event ≥ grade 2 within 12 weeks prior to initiating study treatment
• Any other hemorrhage/bleeding event ≥ grade 3 within 12 weeks prior to initiating study treatment
• History of organ allograft including corneal transplant
• Evidence of bleeding diathesis or coagulopathy
• Documented Gilbert's Syndrome
• Resting systolic blood pressure (BP) < 100 mmHg
• Hypertension defined as systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg despite optimal medical management
• QTc interval > 450 ms on screening 12-lead electrocardiogram (ECG)
• If baseline QTc on screening ECG met exclusion criteria:
• Check calcium, potassium, and magnesium serum levels.
• Correct any identified hypocalcemia, hypokalemia, and/or hypomagnesemia and repeat ECG to reconfirm exclusion of patient due to prolonged QTc interval.
• For patients with heart rate (HR) 60-100 bpm, manual read of QTc was not required.
• For patients with a baseline HR < 60 bpm or > 100 bpm, manual read of the QT interval by a cardiologist was required, with Fridericia correction applied to determine QTc (ie, QTcF).
• Active or clinically significant cardiac disease including any of the following:
• Unstable angina (eg, anginal symptoms at rest) or onset of angina within 3 months prior to initiating study treatment
• Myocardial infarction within 6 months prior to initiating study treatment

Where it is running

• Virginia Commonwealth University/Massey Cancer Center — Richmond, Virginia, United States

Full record on ClinicalTrials.gov

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