Advanced Metastatic Clear Cell Renal Cell Carcinoma (CCRCC) Clinical Trial
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)
| Verified date | September 2023 |
| Source | University of Iowa |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 46 |
| Est. completion date | May 17, 2026 |
| Est. primary completion date | August 23, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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: 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. |
| Country | Name | City | State |
|---|---|---|---|
| United States | University of Iowa Hospitals and Clinics | Iowa City | Iowa |
| Lead Sponsor | Collaborator |
|---|---|
| Yousef Zakharia | Pfizer |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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) | |
| Primary | 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 | Tumor Response rate as assessed by RECIST v.1.1 | After 2 cycles (28 days) | ||
| Secondary | Progression free survival (PFS) | 14 months | ||
| Secondary | Overall survival (OS) | 3 years |