Axitinib and L-Selenomethionine in Treating Patients with Previously Treated Advanced Metastatic Clear Cell Renal Cell Carcinoma

Status: Active

Description

This phase I trial studies the side effects and best dose of L-selenomethionine when given together with axitinib in treating patients with clear cell renal cell carcinoma that has spread from the primary site (place where it started) to other places in the body and usually cannot be cured or controlled with treatment (advanced metastatic). L-selenomethionine may stop the growth of tumor cells by blocking the growth of new blood vessels necessary for tumor growth. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving L-selenomethionine together with axitinib may be a better treatment for advanced metastatic clear cell renal cell carcinoma

Eligibility Criteria

Inclusion Criteria

  • Histologically and radiologically confirmed advanced metastatic CCRCC in patients who have had at least one prior systemic therapy, which can include axitinib for the dose escalation part; in the expansion part, patients with prior axitinib use will be excluded
  • Written and voluntary informed consent
  • At least one Response Evaluation Criteria in Solid Tumors (RECIST)-defined target lesion; patient must have documented disease progression
  • Creatinine level within normal institutional limit, or creatinine clearance > 15 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal, calculated using the Cockcroft-Gault formula)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 X institutional upper limit of normal OR =< 5 x institutional upper limit of normal in cases of liver metastases
  • Total bilirubin =< 1.5 times upper limit of normal (ULN)
  • Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
  • Platelets >= 100 x 10^9/L
  • Hemoglobin >= 7.0 g/dL
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 (fully active, able to carry on all pre-disease performance without restriction), 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, such as light housework or office work) or 2 (ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours)
  • Life expectancy of 12 weeks and more
  • 2 weeks or more since end of previous systemic or radiation treatment (4 weeks or more for bevacizumab plus interferon-alfa); 3 days wash out for palliative radiation

Exclusion Criteria

  • Any other cancer from which the patient has been disease-free for less than 5 years (except treated and cured basal-cell or squamous-cell skin cancer, superficial bladder cancer, or treated carcinoma in situ of the cervix, breast, or bladder and treated localized prostate cancer with undetectable prostate-specific antigen [PSA] for 2 years)
  • Symptomatic untreated metastases in the central nervous system
  • Subject that is pregnancy or lactating
  • Pre-existing uncontrolled hypertension defined as > 150/90 mm Hg with medication
  • Present use or anticipated need for cytochrome P450 (CYP) family 3, subfamily A, polypeptide 4 (3A4)-inhibiting, CYP3A4-inducing drugs (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole, rifampin, phenytoin, carbamazepine, rifabutin, rifapentine, phenobarbital, and St. John's wort, bosentan, efavirenz, etravirine, modafinil, and nafcillin)
  • Myocardial infarction, uncontrolled angina, congestive heart failure, or cerebrovascular accident within previous 6 months; subjects with a history of deep vein thrombosis or pulmonary embolism, at provider discretion
  • Major surgery within 4 weeks of starting study treatment
  • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related disease

Locations & Contacts

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: Active
Contact: Yousef Zakharia
Phone: 319-384-8076
Email: yousef-zakharia@uiowa.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To characterize the safety profile of combining L-selenomethionine (SLM) and axitinib in advanced metastatic clear cell renal cell carcinoma (CCRCC).

II. To define the dose of SLM in combination with a standard dose of axitinib for expansion part 2 and future phase 2 trial (recommended phase II dose [RP2D]).

SECONDARY OBJECTIVES:

I. To determine that the dose of SLM administered is sufficient to alter the expression levels of hypoxia inducible factor 1, alpha subunit (HIF1a), hypoxia inducible factor-2 alpha subunit (HIF2a), vascular endothelial growth factor (VEGF) and their associated micro-ribonucleic acid (RNA)s 210, 155, and LET7b.

II. To determine the SLM concentration when combined with axitinib.

III. To estimate the preliminary efficacy parameters of the combination of SLM and axitinib in terms of:

IIIa. Progression-free survival (PFS).

IIIb. Objective response rate (stable disease [SD]+partial response [PR]+complete response [CR]).

IIIc. Overall survival in patients with advanced metastatic CCRCC.

OUTLINE: This is a dose-escalation study of L-selenomethionine.

Patients receive L-selenomethionine orally (PO) twice daily (BID) on days 1-14. Patients then receive L-selenomethionine PO once daily (QD) and axitinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients tolerating axitinib for at least two consecutive weeks with no adverse reactions > grade 2 considered clinically significant may receive escalated doses of axitinib at the discretion of their treating physician.

After completion of study treatment, patients are followed up at 28 days and then every 6 months thereafter.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Iowa / Holden Comprehensive Cancer Center

Principal Investigator
Yousef Zakharia

Trial IDs

Primary ID 201507716
Secondary IDs NCI-2015-02235
Clinicaltrials.gov ID NCT02535533