Clinical Trials /

SLM + Axitinib for Clear Cell RCC

NCT02535533

Description:

This is a Phase I/II trial for safety and preliminary efficacy of the combination of axitinib and selenomethionine (SLM) for adult patients with advanced metastatic clear cell renal cell carcinoma (CCRCC). This will be a two part study consisting of a dose escalation and expansion study.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: SLM + Axitinib for Clear Cell RCC
  • Official Title: A Therapeutic Trial for Safety and Preliminary Efficacy of the Combination of Axitinib and Seleniomethionine (SLM) for Adult Patients With Advanced Metastatic Clear Cell Renal Cell Carcinoma (CCRCC)

Clinical Trial IDs

  • ORG STUDY ID: 201507716
  • NCT ID: NCT02535533

Conditions

  • Advanced Metastatic Clear Cell Renal Cell Carcinoma (CCRCC)

Interventions

DrugSynonymsArms
Selenomethionine (SLM)Study Treatment
AxitinibStudy Treatment
Selenomethionine (SLM)Study Treatment
AxitinibStudy Treatment

Purpose

This is a Phase 1 trial for safety and preliminary efficacy of the combination of axitinib and selenomethionine (SLM) for adult patients with advanced metastatic clear cell renal cell carcinoma (CCRCC). This will be a two part study consisting of a dose escalation and expansion study.

Detailed Description

      This is a Phase 1 trial for safety and preliminary efficacy of the combination of axitinib
      and selenomethionine (SLM) for adult patients with advanced metastatic clear cell renal cell
      carcinoma (CCRCC). This will be a two part study consisting of a dose escalation and
      expansion study.

      Dose-Escalation Part 1 (6-12 patients) : SLM will be given twice daily for 14 days followed
      by SLM once daily in combination with axitinib 5 mg twice daily with titration according to
      package insert in patients with advanced renal cell carcinoma. Treatment will continue until
      disease progression or unacceptable toxicity.

      Expansion Part 2: In this phase (approximately 19 patients), will be treated at the maximum
      tolerated dose (MTD) of SLM determined in the Escalation Part 1. It will be given orally
      twice daily for 14 days, followed by SLM once daily in combination with axitinib 5 mg twice
      daily with titration according to package insert in patients with advanced renal cell
      carcinoma. Treatment will continue until disease progression or unacceptable toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
Study TreatmentExperimentalDuring the Dose-Escalation Part 1, patients will receive SLM twice daily for 14 days followed by SLM once daily in combination with axitinib 5 mg twice daily with titration according to package insert. Treatment will continue until disease progression or unacceptable toxicity. During the Expansion Part 2, patients will be treated at the maximum tolerated dose (MTD) of SLM determined in the Escalation Part 1. SLM will be given orally twice daily for 14 days followed by SLM once daily in combination with axitinib 5 mg twice daily with titration according to package insert. Treatment will continue until disease progression or unacceptable toxicity.
  • Selenomethionine (SLM)
  • Axitinib
  • Selenomethionine (SLM)
  • Axitinib

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.

          -  Written and voluntary informed consent.

          -  At least one Response Evaluation Criteria In Solid Tumors (RECIST)-defined target
             lesion. *Patient must have documented disease progression.

          -  Renal function (creatinine level within normal institutional limit, or creatinine
             clearance >15 mL/min/1.73 m2 for patients with creatinine levels above institutional
             normal, calculated using the Cockcroft-Gault formula).

          -  Liver function (AST/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 ULN.)

          -  Adequate hematological lab values including: Absolute Neutrophil Count (ANC) ≥ 1.0 x
             109/L, Platelets ≥ 100 x 109/L, Hemoglobin ≥ 9.0 g/dL

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 (fully active, able
             to carry on all pre-disease performance without restriction) or 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).

          -  Age of at least 18 years.

          -  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).

        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 PSA for 2 years).

          -  Symptomatic untreated metastases in the central nervous system.

          -  Subject that is pregnant or lactating

          -  Pre-existing uncontrolled hypertension defined as > 150/90 mm Hg with medication.

          -  Present use or anticipated need for cytochrome P450 (CYP) 3A4-inhibiting,
             CYP3A4-inducing drugs (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir,
             indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and
             voriconazole, rifampin, phenytoin, carbamazepine, rifabutin, rifapentin,
             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 history of deep vein
             thrombosis or pulmonary embolism, at provider discretion.

          -  Myocardial infarction, uncontrolled angina, congestive heart failure, or
             cerebrovascular accident within previous 12 months; and deep vein thrombosis or
             pulmonary embolism within previous 6 months.

          -  Major surgery within 4 weeks of starting study treatment.

          -  Known HIV or acquired immunodeficiency syndrome-related disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (AE) per CTCAE 4.03
Time Frame:After 2 cycles (28 days)
Safety Issue:
Description:The AEs will be summarized and classified by body system and by treatment group. The type, incidence, severity, and causality of each AE, the duration of the event, and any required treatment interventions will be tabulated.

Secondary Outcome Measures

Measure:Tumor Response rate as assessed by RECIST v.1.1
Time Frame:After 2 cycles (28 days)
Safety Issue:
Description:
Measure:Progression free survival (PFS)
Time Frame:14 months
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:3 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Iowa

Trial Keywords

  • Kidney cancer
  • Selenium (Se)

Last Updated

November 7, 2016