CompletedNCT02535533Updated May 6, 2026Results posted

SLM + Axitinib for Clear Cell RCC

A Phase 1/2 interventional study of Selenomethionine (SLM) and Axitinib in Advanced Metastatic Clear Cell Renal Cell Carcinoma (CCRCC), sponsored by Mohammed Milhem. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-06.

Sponsored by Mohammed Milhem · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 45
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study 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.

Read the 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): 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.

Conditions studied

Advanced Metastatic Clear Cell Renal Cell Carcinoma (CCRCC)

Browse trials for

Kidney Neoplasms 954

Keywords

Kidney cancer
Selenium (Se)

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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. 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.

Exclusion criteria

Exclusion Criteria:

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.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 45 participants (actual)

Study arms

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. 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

DrugSelenomethionine (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
DrugAxitinib
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
DrugSelenomethionine (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
DrugAxitinib
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
DrugSelenomethionine (SLM)
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

What researchers measure

Primary outcomes

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.
Time frame: 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%.
Time frame: 14 days

Secondary outcomes

Overall Response Rate
The overall response rate is the percentage of patients with a confirmed complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: From treatment initiation to treatment end, up to 3 years
Progression-Free Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: From treatment initiation up to 2 years
Overall Survival
Overall survival is defined as the time from study treatment initiation to death due to any cause. Patients still alive were censored at the last date known to be alive.
Time frame: From treatment initiation up to 3 years

Results

Posted May 6, 2026

Participant flow

Participant flow — Overall Study
Milestone	Dose Escalation Phase 1: SLM 2500mcg / Axitinib 5mg	Dose Escalation Phase 1: SLM 3000mcg / Axitinib 5mg	Dose Escalation Phase 1: SLM 4000mcg / Axitinib 5mg	Dose Expansion Phase 2: SLM 4000mcg / Axitinib 5mg	Pilot Cohort-Dose Level 3 (BSA-adjusted)	Pilot Cohort-Level 4 Dose (BSA-adjusted)
Started	3	5	7	20	8	2
Completed	0	0	2	4	2	2
Not completed	3	5	5	16	6	0
Withdrew: Adverse event	1	0	0	3	1	0
Withdrew: Alternative therapy	0	0	0	1	0	0
Withdrew: Disease progression	2	3	5	11	4	0
Withdrew: Withdrawal by subject	0	1	0	0	1	0
Withdrew: Other complicating disease	0	1	0	1	0	0

Outcome measures

PrimaryIncidence 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.

Time frame:: After 2 cycles (28 days)
Reported as:: Count of participants · Participants

Incidence of Adverse Events (AE) Per CTCAE 4.03
Participants	Dose-Escalation Phase I: SLM 2500mcg / Axitnib 5mg	Dose-Escalation Phase I: SLM 3000mcg / Axitnib 5mg	Dose-Escalation Phase I: SLM 4000mcg / Axitnib 5mg	Dose Expansion Phase 2: SLM 4000mcg / Axitnib 5mg	Pilot Cohort-Dose Level 3 (BSA-adjusted)	Pilot Cohort-Dose Level 4 (BSA-adjusted)
Incidence of Adverse Events (AE) Per CTCAE 4.03	3	5	7	20	8	2

PrimaryPilot 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%.

Time frame:: 14 days
Reported as:: Count of participants · Participants

Pilot Phase - Determine Dose-concentration Relationship and Estimate the Effective Dose of SLM (Informed by Preclinical Data) Using the Continual Reassessment Method (CRM).
Participants	Pilot Cohort-Dose Level 3 (BSA-adjusted)	Pilot Cohort-Dose Level 4 (BSA-adjusted)
Pilot Phase - Determine Dose-concentration Relationship and Estimate the Effective Dose of SLM (Informed by Preclinical Data) Using the Continual Reassessment Method (CRM).	0	0

SecondaryOverall Response Rate

The overall response rate is the percentage of patients with a confirmed complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Time frame:: From treatment initiation to treatment end, up to 3 years
Reported as:: Count of participants · Participants

Overall Response Rate
Participants	Dose-Escalation / Dose Expansion Part 1 & 2
Overall Response Rate	15

SecondaryProgression-Free Survival

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Time frame:: From treatment initiation up to 2 years
Reported as:: Median · months

Progression-Free Survival
months	Dose-Escalation / Dose Expansion Part 1 & 2
Progression-Free Survival	14.8 (6.0 to 20.7)

SecondaryOverall Survival

Overall survival is defined as the time from study treatment initiation to death due to any cause. Patients still alive were censored at the last date known to be alive.

Time frame:: From treatment initiation up to 3 years
Reported as:: Median · months

Overall Survival
months	Dose-Escalation / Dose Expansion Part 1 & 2
Overall Survival	19.6 (12.0 to 40.6)

Adverse events

Collected over All adverse events (regardless of grade and attribution) observed from initiation of treatment and for up to 30 days after last dose of study drug, up to 3 years. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Period 1: Phase 1: SLM 2500	3/3 (100%)	1/3 (33.3%)	3/3 (100%)
Period 2: Phase 1: SLM 3000	3/5 (60%)	4/5 (80%)	5/5 (100%)
Period 3: Phase 1: SLM 4000	5/7 (71.4%)	7/7 (100%)	7/7 (100%)
Period 4: Phase 2: SLM 4000	16/20 (80%)	5/20 (25%)	20/20 (100%)
Period 5: Pilot: SLM Dose Level 3	5/8 (62.5%)	4/8 (50%)	8/8 (100%)
Period 6: Pilot: SLM Dose Level 4	2/2 (100%)	0/2 (0%)	2/2 (100%)

Most frequent serious events

Showing 10 of 33

Most frequent serious events
Event	Period 1: Phase 1: SLM 2500	Period 2: Phase 1: SLM 3000	Period 3: Phase 1: SLM 4000	Period 4: Phase 2: SLM 4000	Period 5: Pilot: SLM Dose Level 3	Period 6: Pilot: SLM Dose Level 4
Bronchopulmonary hemorrhageRespiratory, thoracic and mediastinal disorders	1/3	0/5	0/7	0/20	0/8	0/2
DiarrheaGastrointestinal disorders	0/3	0/5	0/7	0/20	2/8	0/2
Abdominal painGastrointestinal disorders	0/3	1/5	0/7	1/20	0/8	0/2
PainGeneral disorders and administration site conditions	0/3	1/5	0/7	0/20	0/8	0/2
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specifyNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/3	1/5	0/7	0/20	1/8	0/2
Ischemia cerebrovascularNervous system disorders	0/3	1/5	0/7	0/20	0/8	0/2
Thromboembolic eventVascular disorders	0/3	1/5	0/7	0/20	1/8	0/2
Gastrointestinal disorders - Other, specifyGastrointestinal disorders	0/3	0/5	1/7	1/20	0/8	0/2
FatigueGeneral disorders and administration site conditions	0/3	0/5	1/7	0/20	0/8	0/2
FeverGeneral disorders and administration site conditions	0/3	0/5	1/7	0/20	0/8	0/2

Most frequent other events

Showing 10 of 188

Most frequent other events
Event	Period 1: Phase 1: SLM 2500	Period 2: Phase 1: SLM 3000	Period 3: Phase 1: SLM 4000	Period 4: Phase 2: SLM 4000	Period 5: Pilot: SLM Dose Level 3	Period 6: Pilot: SLM Dose Level 4
NauseaGastrointestinal disorders	1/3	2/5	6/7	10/20	5/8	2/2
FatigueGeneral disorders and administration site conditions	3/3	3/5	6/7	17/20	6/8	2/2
General disorders and administration site conditions - Other, specifyGeneral disorders and administration site conditions	0/3	2/5	4/7	1/20	1/8	2/2
Palmar-plantar erythrodysesthesia syndromeSkin and subcutaneous tissue disorders	0/3	0/5	1/7	8/20	2/8	2/2
PruritusSkin and subcutaneous tissue disorders	0/3	0/5	0/7	4/20	1/8	2/2
AnorexiaMetabolism and nutrition disorders	0/3	3/5	5/7	10/20	7/8	0/2
HypertensionVascular disorders	0/3	2/5	6/7	9/20	5/8	1/2
HeadacheNervous system disorders	0/3	4/5	2/7	3/20	2/8	1/2
DiarrheaGastrointestinal disorders	2/3	3/5	5/7	15/20	4/8	1/2
VomitingGastrointestinal disorders	0/3	1/5	5/7	5/20	4/8	1/2

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Dose Escalation Phase 1: SLM 2500mcg / Axitinib 5mg	Dose Escalation Phase 1: SLM 3000mcg / Axitinib 5mg	Dose Escalation Phase 1: SLM 4000mcg / Axitinib 5mg	Dose Expansion Phase 2: SLM 4000mcg / Axitinib 5mg	Pilot Cohort-Dose Level 3 (BSA-adjusted)	Pilot Cohort-Level 4 Dose (BSA-adjusted)	Total
<=18 years	0	0	0	0	0	0	0
Between 18 and 65 years	3	3	5	12	6	0	29
>=65 years	0	2	2	8	2	2	16

Age, Continuous
Age, Continuous(years)	Dose Escalation Phase 1: SLM 2500mcg / Axitinib 5mg	Dose Escalation Phase 1: SLM 3000mcg / Axitinib 5mg	Dose Escalation Phase 1: SLM 4000mcg / Axitinib 5mg	Dose Expansion Phase 2: SLM 4000mcg / Axitinib 5mg	Pilot Cohort-Dose Level 3 (BSA-adjusted)	Pilot Cohort-Level 4 Dose (BSA-adjusted)	Total
Mean	55 (53 to 57)	64 (55 to 74)	59 (50 to 72)	62 (39 to 76)	58 (40 to 70)	69 (69 to 70)	61 (39 to 76)

Sex: Female, Male
Sex: Female, Male(Participants)	Dose Escalation Phase 1: SLM 2500mcg / Axitinib 5mg	Dose Escalation Phase 1: SLM 3000mcg / Axitinib 5mg	Dose Escalation Phase 1: SLM 4000mcg / Axitinib 5mg	Dose Expansion Phase 2: SLM 4000mcg / Axitinib 5mg	Pilot Cohort-Dose Level 3 (BSA-adjusted)	Pilot Cohort-Level 4 Dose (BSA-adjusted)	Total
Female	0	1	1	3	3	2	10
Male	3	4	6	17	5	0	35

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Dose Escalation Phase 1: SLM 2500mcg / Axitinib 5mg	Dose Escalation Phase 1: SLM 3000mcg / Axitinib 5mg	Dose Escalation Phase 1: SLM 4000mcg / Axitinib 5mg	Dose Expansion Phase 2: SLM 4000mcg / Axitinib 5mg	Pilot Cohort-Dose Level 3 (BSA-adjusted)	Pilot Cohort-Level 4 Dose (BSA-adjusted)	Total
Hispanic or Latino	0	0	0	0	0	0	0
Not Hispanic or Latino	3	5	7	19	8	2	44
Unknown or Not Reported	0	0	0	1	0	0	1

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Dose Escalation Phase 1: SLM 2500mcg / Axitinib 5mg	Dose Escalation Phase 1: SLM 3000mcg / Axitinib 5mg	Dose Escalation Phase 1: SLM 4000mcg / Axitinib 5mg	Dose Expansion Phase 2: SLM 4000mcg / Axitinib 5mg	Pilot Cohort-Dose Level 3 (BSA-adjusted)	Pilot Cohort-Level 4 Dose (BSA-adjusted)	Total
American Indian or Alaska Native	0	0	0	0	0	0	0
Asian	0	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0
Black or African American	0	0	0	0	0	0	0
White	3	5	7	19	8	2	44
More than one race	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	1	0	0	1

Region of Enrollment
Region of Enrollment(participants)	Dose Escalation Phase 1: SLM 2500mcg / Axitinib 5mg	Dose Escalation Phase 1: SLM 3000mcg / Axitinib 5mg	Dose Escalation Phase 1: SLM 4000mcg / Axitinib 5mg	Dose Expansion Phase 2: SLM 4000mcg / Axitinib 5mg	Pilot Cohort-Dose Level 3 (BSA-adjusted)	Pilot Cohort-Level 4 Dose (BSA-adjusted)	Total
United States	3	5	7	20	8	2	45

Study locations

1 site

University of Iowa Hospitals and Clinics
Iowa City, Iowa 52242, United States

References and documents

Study documents

Protocol and statistical analysis plan · Dec 28, 2022
Informed consent form · May 15, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Registry details

Key details

Study ID: NCT02535533
Lead sponsor: Mohammed Milhem
Collaborators: Pfizer
Responsible party: Mohammed Milhem (Clinical Professor, University of Iowa) — Sponsor-investigator
First posted: Aug 28, 2015
Start date: Jan 2016
Primary completion: Aug 22, 2023
Completion: Apr 4, 2025
Results posted: May 6, 2026
Last update: May 6, 2026

Study contacts

Mohammed Milhem, MBBS

principal investigator · University of Iowa Hospitals & Clinics

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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