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Treatment Agent: Pembrolizumab

Synopsis: The purpose of this study is to:

• to evaluate and compare the safety, tolerability and anti-tumor activity of the research study drug  pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy
• to test the effectiveness of the research study drug compared to placebo (look-alike with no active ingredients).

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• Has histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features.
• Female participants of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study treatment.
• Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study treatment through 120 days after the last dose of study treatment.
• Has intermediate-high risk, high risk, or M1 NED RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading status:
  1. Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, Any Grade, N0, M0
  2. High risk RCC: pT4, Any Grade N0, M0; pT, Any stage, Any Grade, N+, M0
  3. M1 NED RCC (participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at the time of nephrectomy)
• Has received no prior systemic therapy for advanced RCC (except nephrectomy or metastasectomy).
• Has undergone a partial nephroprotective or radical complete nephrectomy (and complete resection of metastatic lesion[s] in M1 NED participants) with negative surgical margins.
• Must have undergone a nephrectomy (and metastasectomy for M1 NED) ≥28 days prior to signing informed consent and must be randomized ≤12 weeks after surgery.
• Must be tumor-free as assessed by the Investigator and validated by either computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain and chest, abdomen, and pelvis and a bone scan ≤28 days from randomization.
• Has provided adequate tissue from the primary tumor (and resected metastatic lesion for M1 NED participants).
• Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.
• Has adequate organ function.

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• Has had major surgery, other than nephrectomy plus resection of pre-existing metastases for M1 NED participants, within 12 weeks prior to randomization.
• Has received prior radiotherapy for RCC.
• Has residual thrombus post nephrectomy in the vena renalis or vena cava.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is allowed.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer, or in situ breast cancer that has undergone potentially curative therapy.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has known active hepatitis B or hepatitis C virus infection.
• Has a known history of active tuberculosis (Bacillus tuberculosis).
• Has had a prior solid organ transplant.
• Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the Screening visit through 120 days after the last dose of study treatment.
• Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial.
• Has received prior anticancer therapy, monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before first dose of study treatment or not recovered (i.e., must be ≤ Grade 1 or at Baseline) from AEs due to previously administered agents.
• Has received a live vaccine within 30 days prior to the first dose of study treatment.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

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Physician

Yacoub Faroun, MD

 

Study Coordinator

Megan Gavinski, BS
484-503-4157

Megan.Gavinski@sluhn.org

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Treatment Agent: Abexinostat

Synopsis: The purpose of this study is to compare the safety and effectiveness of pazopanib plus abexinostat to that of pazopanib plus placebo. This will be accomplished by monitoring how your disease is progressing. To do this, the study doctor and staff will assess how the disease affects your ability to complete daily living activities, test your blood for levels of thyroid hormone and liver enzymes; review results from scans of your tumor(s) and electrocardiogram (ECG) tests (painless, non-invasive tests that show how your heart works); and monitor your general health and vital signs. There will also be a test to find out how much of the medication is in your blood.

Abexinostat has been used in 16 other experimental studies that the Sponsor has conducted. Altogether, 487 people have been exposed either to abexinostat alone or to abexinostat combined with other treatments. One completed study used the same drugs that will be used in this study: abexinostat and pazopanib. The study was done in patients with renal cell carcinoma and it was found that the drugs were tolerated well.

This is a study to find out whether the investigational new drug, abexinostat, will improve the effects of pazopanib (the approved drug) in treating renal cell carcinoma. Because we do not know if abexinostat will improve the effects of pazopanib in treating renal cell carcinoma, we need to compare pazopanib plus abexinostat and pazopanib plus placebo. Participants with renal cell carcinoma who agree to be in this study will take pazopanib and either tablets containing abexinostat or placebo. A placebo is a tablet that does not contain active study medication(s).

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• Patients aged ≥ 18 years at time of study entry.
• Patients have histologically confirmed RCC with clear cell component.
• Patients have locally advanced and unresectable or metastatic disease.
• Measurable disease as assessed only by the investigator (not verified by IRC) according to RECIST version 1.1.
• Patients must not have had any prior vascular endothelial growth factor (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.
• Patients have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patients have adequate baseline organ function.
• Patients have adequate baseline hematologic function
• Patient must be at least 2 weeks from last systemic treatment or dose of radiation prior to date of randomization.

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• Has persistent clinically significant toxicities (Grade ≥ 2; per NCI CTCAE version 5 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).
• 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.
• 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.
• Poorly controlled hypertension, defined as systolic blood pressure ≥ 160 or diastolic blood pressure ≥ 100 mmHg. Use of anti-hypertensives and rescreening is permitted.
• A new pulmonary embolism or deep venous thrombosis diagnosed within 3 months prior to randomization.
• Has a QTcF interval > 480 msec.
• New York Heart Association Class III or IV congestive heart failure.
• Use of prohibited medication within 7 days or 5 half-lives, whichever is shorter, prior to first dose of study drug.

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