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. In addition, a pilot group of 10 subjects will have SLM dose calculated based on patients' body surface area (BSA) to characterize the dose-concentration relationship and estimate the effective administered dose of selenium necessary to achieve the target blood concentration range informed by preclinical data.

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
Selenomethionine (SLM)Study Treatment

Purpose

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. In addition, a pilot group of 10 subjects will have SLM dose calculated based on patients' body surface area (BSA) to characterize the dose-concentration relationship and estimate the effective administered dose of selenium necessary to achieve the target blood concentration range informed by preclinical data.

Detailed Description

      This is a Phase I trial for safety and preliminary efficacy of the combination of axitinib
      and SLM for adult patients with advanced metastatic CCRCC. This will be a two part study
      consisting of a dose escalation and expansion study.

      Dose-Escalation Part 1 (6-12 patients): THIS PHASE HAS BEEN COMPLETED. SLM will be given
      twice daily for 14 days followed by once daily dosing 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. The
      MTD was determined to be 4000 mcg SLM.

      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 once daily dosing 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.

      A pilot group of 10 subjects will have SLM dose calculated based on patients' BSA to
      characterize the dose-concentration relationship and estimate the effective administered dose
      of selenium necessary to achieve the target blood concentration range informed by preclinical
      data.
    

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 as 4000 mcg SLM. 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. During the Pilot Phase, dosing will begin at dose level 3 (4000, 5000, or 6000 mcg SLM calculated based on patients' BSA). SLM will be given orally twice daily for 14 days. Each cohort will enroll 2 evaluable patients.
  • Selenomethionine (SLM)
  • Axitinib
  • Selenomethionine (SLM)
  • Axitinib
  • Selenomethionine (SLM)

Eligibility Criteria

        Inclusion Criteria:

        Each patient must meet all of the following criteria to be enrolled in this study:

          -  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 and pilot phases, patients with prior axitinib are
             allowed, as long as the last dose of axitinib was longer than 6 months ago. 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 ≥ 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).

          -  Age of at least 18 years.

          -  Life expectancy of 12 weeks and more.

          -  2 weeks or more since end of previous systemic treatment (4 weeks or more for
             bevacizumab plus interferon-alfa). 3 days wash out for palliative radiation.

          -  Must have a safely accessible biopsy per treating physician and the provider
             performing that biopsy. And patient must agree to have this biopsy done as outlined in
             the calendar.

        Exclusion Criteria:

        Patients eligible for this study must not meet any of the following 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.

          -  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/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Yousef Zakharia

Trial Keywords

  • Kidney cancer
  • Selenium (Se)

Last Updated

November 3, 2020