SLM + Axitinib for Clear Cell RCC

NCT02535533 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 201507716
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Metastatic Clear Cell Renal Cell Carcinoma (CCRCC)

Keywords

Kidney cancer; Selenium (Se)

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events (AE) Per CTCAE 4.03

  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.

  After 2 cycles (28 days)

• Pilot Phase - Determine Dose-concentration Relationship and Estimate the Effective Dose of SLM (Informed by Preclinical Data) Using the Continual Reassessment Method (CRM).

  Dose escalation for this pilot study will be conducted using a CRM in which the probability of exceeding a blood selenium concentration of 45 µM on Day 14 is being modeled. Prior probabilities of exceeding a blood selenium concentration of 45 µM on Day 14 were estimated based on preclinical and preliminary data from the initial trial. A one parameter logistic model with intercept set at 3 and an initial value of 1 for the slope will be used to estimate the dose-concentration relationship through sequential recursive Bayesian assessment. The target probability of exceeding 45 µM is ≤20%.

  14 days

Secondary Outcomes (3)

• Overall Response Rate

  From treatment initiation to treatment end, up to 3 years

• Progression-Free Survival

  From treatment initiation up to 2 years

• Overall Survival

  From treatment initiation up to 3 years

Study Arms (1)

Study Treatment

EXPERIMENTAL

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. 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.

Drug: Selenomethionine (SLM); Drug: Axitinib

Interventions

Axitinib DRUG

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

Study Treatment

Selenomethionine (SLM) DRUG

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

Study Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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. Patient must agree to have this biopsy done as outlined in the calendar. If patient does not have safely accessible biopsy, the patient may still be enrolled per investigator discretion.

You may not qualify if:

• Patients eligible for this study must not meet any of the following criteria:
• Patients with prior malignancies of the same or different tumor type in the last 5 years and patients with concurrent malignancies of the same or different tumor type UNLESS the natural history of the disease or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational drug.
• 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.

Sponsors & Collaborators

• Mohammed Milhem: lead
• Pfizer: collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Kidney Neoplasms

Interventions

Selenomethionine; Axitinib

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Organoselenium Compounds; Organic Chemicals; Methionine; Amino Acids, Sulfur; Sulfur Compounds; Amino Acids; Amino Acids, Peptides, and Proteins; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Mohammed Milhem, MBBS
• Organization: University of Iowa

mohammed-milhem@uiowa.edu

319-356-2324

Study Officials

• Mohammed Milhem, MBBS

  University of Iowa Hospitals & Clinics

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: August 17, 2015
• First Posted: August 28, 2015
• Study Start: January 1, 2016
• Primary Completion: August 22, 2023
• Study Completion: April 4, 2025
• Last Updated: May 6, 2026
• Results First Posted: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)