Clinical trial · Interventional
Bevacizumab, Sorafenib Tosylate, and Temsirolimus in Treating Patients With Metastatic Kidney Cancer
The BeST Trial: A Randomized Phase II Study of VEGF, RAF Kinase, and mTOR Combination Targeted Therapy (CTT) With Bevacizumab, Sorafenib, and Temsirolimus in Advanced Renal Cell Carcinoma
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This randomized phase II trial studies different combinations of bevacizumab, temsirolimus, and sorafenib tosylate to see how well they work compared with bevacizumab alone in treating patients with kidney cancer that has spread to other places in the body. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab and sorafenib tosylate may stop the growth of tumor cells by blocking blood flow to the tumor. Temsirolimus and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving different combinations of bevacizumab, sorafenib tosylate, and temsirolimus may be more effective than bevacizumab alone in treating metastatic kidney cancer.
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Clear Cell Renal Cell Carcinoma | Clear Cell Renal Cell Carcinoma | ONTOLOGY_EXACT | 0.98 |
| Recurrent Renal Cell Carcinoma | Renal Cell Carcinoma | CURATED_BROADER | 0.80 |
| Stage IV Renal Cell Cancer AJCC v7 | Renal Cell Carcinoma | CURATED_BROADER | 0.80 |
Interventions
Interventions (5)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Bevacizumab | Biological | Bevacizumab | ALIAS |
| Laboratory Biomarker Analysis | Other | — | UNRESOLVED |
| Pharmacological Study | Other | — | UNRESOLVED |
| Sorafenib Tosylate | Drug | Sorafenib Tosylate | ALIAS |
| Temsirolimus | Drug | Temsirolimus | ALIAS |
Design
Arms and outcomes
Arms (4)
- type
- ACTIVE_COMPARATOR
- label
- Arm A (bevacizumab)
- description
- Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15.
- interventionNames
- Biological: Bevacizumab
- Other: Laboratory Biomarker Analysis
- Other: Pharmacological Study
- type
- EXPERIMENTAL
- label
- Arm B (bevacizumab and temsirolimus)
- description
- Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 and bevacizumab as in Arm A.
- interventionNames
- Biological: Bevacizumab
- Other: Laboratory Biomarker Analysis
- Other: Pharmacological Study
- Drug: Temsirolimus
- type
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Patients will be required to have the clear cell variant of renal cell carcinoma with less than 25% of any other histology (including, but not limited to, papillary or chromophobe or oncocytic); there must be histologic confirmation by treating center of either primary or metastatic lesion * Patients will be required to have measurable metastatic disease that is not curable by standard radiation therapy or surgery; all sites must be assessed within 4 weeks prior to study entry * Previous nephrectomy is required with the following exceptions: * Primary tumor =\< 5 cm, or * Extensive liver (\> 30% of liver parenchymal) or multiple (\> 5) bone metastases, making nephrectomy a clinically questionable procedure * Unresectable primary tumor due to invasion into adjacent organs or encasing the aorta or vena cava * No prior cytotoxic chemotherapy; a maximum of one prior regimen of either vaccine or cytokine-based immunotherapy disease is permitted * No prior anti-angiogenic therapy including, but not limited to, SU11248, ZD6474 or VEGF Trap; no prior therapy with bevacizumab, mammalian target of rapamycin (mTOR) inhibitors (including, but not limited to, temsirolimus), or sorafenib will be allowed; thalidomide or interferon alpha (IFNalpha) are allowed either for adjuvant therapy or stage IV disease * No immunotherapy within 4 weeks of randomization; toxicities from immunotherapy must have resolved and a minimum of two weeks must pass prior to enrollment * Prior radiation therapy is permitted, but toxicities from radiation must have resolved and a minimum of 2 weeks must pass prior to randomization * No history or clinical evidence of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastasis, or history of stroke within the past 48 weeks * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy of greater than 12 weeks * Hemoglobin (Hgb) \>= 9.0 g/dL (transfusions allowed prior to enrollment) * White blood count (WBC) \>= 3,000/mm\^3 * Absolute granulocyte count (AGC) \>= 1,200/mm\^3 * Platelet count \>= 100,000/mm\^3 * Serum creatinine =\< 1.5 x upper limit of normal (ULN) or serum creatinine clearance (CrCl) \>= 55 ml/min * Total bilirubin =\< 1.5 x ULN * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN (or =\< 5.0 x ULN in the presence of liver metastases) * International normalized ratio (INR) =\< 1.5 * Activated partial thromboplastin time (aPTT) within normal limits * Fasting cholesterol \< 350 mg/dL (9.0 mmol/L) * Fasting triglycerides \< 400 mg/dL (4.56 mmol/L) * Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, and ductal or lobular carcinoma in situ of the breast; patients with other malignancies are eligible if they have been continuously disease-free for \>= 5 years prior to the time of randomization * No history of allergic reactions attributed to Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biologic composition to sorafenib, temsirolimus or bevacizumab * No history of bleeding diathesis or coagulopathy * Any condition that impairs patient's ability to swallow pills will make patient ineligible * No major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization * No anticipated need for major surgery during the course of the study * No current or recent (within 4 weeks of enrollment) use of full-dose of anticoagulants or thrombolytic agents (except as required to maintain patency of preexisting or permanent indwelling IV catheters, for those patients receiving warfarin, INR must be =\< 1.5) * No clinically significant cardiovascular disease, defined as one of the following: * Patients with uncontrolled hypertension (blood pressure \> 150/100 mm/Hg at the time of enrollment); patients with hypertension and blood pressure =\< 150/100 mm/Hg on stable antihypertensive regimen are eligible * Myocardial infarction or unstable angina \< 24 weeks prior to registration * New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris * Grade II or greater peripheral vascular disease * No serious, non-healing wound, ulcer, or bone fracture * No significant proteinuria at baseline; urine protein must be screened within 2 weeks prior to randomization by urine analysis for urine protein creatinine (UPC) ratio; if UPC ratio is \> 0.5, 24-hour urine protein is to be obtained and the level must be \< 1000 mg for patient enrollment * NOTE: UPC ratio of spot urine is an estimation of the 24 urine protein excretion; a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 gm * No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on day 0 or psychiatric illness/social situations that would limit compliance with study requirements * Patients currently taking any of the following cytochrome P450 enzyme-inducing drugs are ineligible: * Phenytoin * Carbamazepine * Phenobarbital * Rifampin * Pregnant and breastfeeding women are excluded from the study; breastfeeding should be discontinued while receiving therapy; patients must have pregnancy test within 7 days prior to patient randomization if woman is of child-bearing capacity * Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study
References
Publications (1)
- DERIVEDFlaherty KT, Manola JB, Pins M, McDermott DF, Atkins MB, Dutcher JJ, George DJ, Margolin KA, DiPaola RS. BEST: A Randomized Phase II Study of Vascular Endothelial Growth Factor, RAF Kinase, and Mammalian Target of Rapamycin Combination Targeted Therapy With Bevacizumab, Sorafenib, and Temsirolimus in Advanced Renal Cell Carcinoma--A Trial of the ECOG-ACRIN Cancer Research Group (E2804). J Clin Oncol. 2015 Jul 20;33(21):2384-91. doi: 10.1200/JCO.2015.60.9727. Epub 2015 Jun 15. PMID 26077237