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SLM + Axitinib for Clear Cell RCC

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ClinicalTrials.gov Identifier: NCT02535533
Recruitment Status : Recruiting
First Posted : August 28, 2015
Last Update Posted : June 20, 2019
Sponsor:
Information provided by (Responsible Party):
Yousef Zakharia, University of Iowa

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced Metastatic Clear Cell Renal Cell Carcinoma (CCRCC) Drug: Selenomethionine (SLM) Drug: Axitinib Phase 1 Phase 2

Detailed 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.

Dose-Escalation Part 1 (6-12 patients) : SLM will be given twice daily for 14 days followed by SLM 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 maximum tolerated dose (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 as 4000 mcg SLM. 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : January 2016
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2023


Arm Intervention/treatment
Experimental: Study Treatment

During 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.

Drug: Selenomethionine (SLM)
SLM administrated 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

Drug: Axitinib
Following SLM administrated orally twice daily for 14 days, SLM once daily in combination with Axitinib 5 mg twice daily with titration according to package insert

Drug: Selenomethionine (SLM)
Maximum tolerated dose (MTD) of SLM determined in the Escalation Part 1 (4000 mcg SLM) 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

Drug: Axitinib
Following maximum tolerated dose (MTD) of SLM determined in the Escalation Part 1 (4000 mcg SLM) given orally twice daily for 14 days, SLM once daily in combination with axitinib 5 mg twice daily with titration according to package insert




Primary Outcome Measures :
  1. Incidence of adverse events (AE) per CTCAE 4.03 [ Time Frame: After 2 cycles (28 days) ]
    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 :
  1. Tumor Response rate as assessed by RECIST v.1.1 [ Time Frame: After 2 cycles (28 days) ]
  2. Progression free survival (PFS) [ Time Frame: 14 months ]
  3. Overall survival (OS) [ Time Frame: 3 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • 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 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02535533


Contacts
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Contact: Yousef Zakharia, MD 319-384-8076 yousef-zakharia@uiowa.edu

Locations
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United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Yousef Zakharia, MD    319-384-8076    yousef-zakharia@uiowa.edu   
Sponsors and Collaborators
Yousef Zakharia
Investigators
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Principal Investigator: Yousef Zakharia, MD University of Iowa Hospitals & Clinics

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Responsible Party: Yousef Zakharia, Clinical Assistant Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT02535533     History of Changes
Other Study ID Numbers: 201507716
First Posted: August 28, 2015    Key Record Dates
Last Update Posted: June 20, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Yousef Zakharia, University of Iowa:
Kidney cancer
Selenium (Se)
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Selenium
Axitinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antioxidants
Protective Agents
Physiological Effects of Drugs
Trace Elements
Micronutrients
Nutrients
Growth Substances