Pembrolizumab + Axitinib for Kidney Cancer
(NEOPAX Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Colorado, Denver
Must not be taking: Steroids, Immunosuppressants, CYP3A4/5 inducers
Disqualifiers: Immunodeficiency, Autoimmune disease, CNS metastases, others
Stay on Your Current Meds
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The primary objective of this study is to evaluate whether the combination of Pembrolizumab and Axitinib given in the neoadjuvant setting can change the Inferior Vena Cava Tumor Thrombus burden. A decrease in the size of the tumor thrombus can potentially lead to decrease in surgical complications, improve patient related health outcomes, and improve long term outcomes such as progression free survival and overall survival.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot use certain drugs that strongly affect liver enzymes (CYP3A4/5 inhibitors or inducers) within 7 days before joining the study.
What data supports the effectiveness of the drug combination of Pembrolizumab and Axitinib for kidney cancer?
Research shows that the combination of Pembrolizumab and Axitinib is effective for advanced kidney cancer, with a 73% response rate in patients who have not been treated before. This combination also improves survival and delays cancer progression compared to another drug, sunitinib.
12345Is the combination of Pembrolizumab and Axitinib safe for humans?
The combination of Pembrolizumab and Axitinib has been studied for safety in patients with advanced kidney cancer. Some side effects include diarrhea, liver issues, fatigue, and heart-related problems, which require careful management by healthcare providers.
14678How is the drug combination of pembrolizumab and axitinib unique for kidney cancer?
The combination of pembrolizumab and axitinib is unique for treating advanced kidney cancer because it combines an immune checkpoint inhibitor (pembrolizumab) with a VEGF-R-TKI (axitinib), which has shown better outcomes in terms of tumor response and survival compared to the standard treatment with sunitinib.
1291011Eligibility Criteria
Adults with clear cell renal cell carcinoma and a tumor thrombus in the inferior vena cava who are candidates for surgery. They must have good performance status, controlled blood pressure, no major surgeries or radiation therapy within specific time frames before enrollment, and not be on certain medications that affect immune response or blood clotting.Inclusion Criteria
Stated willingness to comply with all study procedures and be available for the duration of the study
My urologist considers me a good candidate for immediate surgery.
I am a candidate for and agree to have kidney surgery as advised by my urologist.
+10 more
Exclusion Criteria
I haven't had major surgery or radiation therapy in the last month.
I have had heart problems in the last year.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study by subject self-report
+21 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive neoadjuvant therapy with Pembrolizumab and Axitinib for 12 weeks
12 weeks
4 cycles of therapy with visits every 21 days
Surgery
Participants undergo definitive surgery within 2 weeks after the end of treatment scan
2 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment, including surgical complications and adverse events
4 weeks
Post-operative monitoring up to 30 days
Long-term Follow-up
Participants are monitored for progression-free survival and overall survival up to 1 year
12 months
Participant Groups
The trial is testing if Pembrolizumab combined with Axitinib can reduce the size of kidney cancer-related blood clots in the vein before surgery. The goal is to see if this pre-surgery treatment leads to fewer surgical complications and better long-term health outcomes like survival without cancer progression.
1Treatment groups
Experimental Treatment
Group I: Combination Pembrolizumab and AxitinibExperimental Treatment2 Interventions
Neoadjuvant therapy with the combination of Pembrolizumab and Axitinib will be given for eligible RCC patients with an IVC TT for a total of 12 weeks. Patients will then undergo imaging with a contrast enhanced, diffusion weighted imaging MRI of the abdomen to evaluate the IVC TT response. A CT chest will also be done to ensure there is no progression of disease. Patients can undergo definitive surgery per treating Urologist within 2 weeks (+/- 7 days) after end of treatment scan.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Colorado Cancer CenterAurora, CO
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Who Is Running the Clinical Trial?
University of Colorado, DenverLead Sponsor
Cancer League of ColoradoCollaborator
References
Axitinib plus Pembrolizumab Is Effective in Renal Cell Carcinoma. [2019]Axitinib plus pembrolizumab has a 73% response rate in previously untreated advanced renal cell carcinoma.
Real-World Therapy Management and Outcomes of First-Line Axitinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma in the United States. [2022]Combination axitinib plus pembrolizumab is a standard of care in the first-line treatment of patients with advanced clear cell renal cell carcinoma (RCC). This analysis describes the clinical characteristics, treatment management and outcomes of patients receiving first-line (1L) axitinib plus pembrolizumab in a real-world US setting.
Pembrolizumab plus axitinib versus sunitinib in metastatic renal cell carcinoma: outcomes of Japanese patients enrolled in the randomized, phase III, open-label KEYNOTE-426 study. [2022]In the phase III open-label KEYNOTE-426 (NCT02853331) study, first-line pembrolizumab and axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC). KEYNOTE-426 evaluated patients enrolled from 25 sites in Japan.
Axitinib plus pembrolizumab in patients with advanced renal-cell carcinoma: Long-term efficacy and safety from a phase Ib trial. [2021]Axitinib plus pembrolizumab showed superior overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) versus sunitinib in a randomised phase III trial in patients with advanced renal-cell carcinoma (RCC). We report long-term efficacy and safety of the axitinib/pembrolizumab from the phase I trial (NCT02133742), after 46-55 months from study initiation (data cut-off date, 23rd July 2019).
Angiogenic and Immune-Related Biomarkers and Outcomes Following Axitinib/Pembrolizumab Treatment in Patients with Advanced Renal Cell Carcinoma. [2023]Combined axitinib/pembrolizumab is approved for advanced renal cell carcinoma (aRCC). This exploratory analysis examined associations between angiogenic and immune-related biomarkers and outcomes following axitinib/pembrolizumab treatment.
Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. [2023]Previous studies combining PD-1 checkpoint inhibitors with tyrosine kinase inhibitors of the VEGF pathway have been characterised by excess toxicity, precluding further development. We hypothesised that axitinib, a more selective VEGF inhibitor than others previously tested, could be combined safely with pembrolizumab (anti-PD-1) and yield antitumour activity in patients with treatment-naive advanced renal cell carcinoma.
Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. [2021]The first interim analysis of the KEYNOTE-426 study showed superior efficacy of pembrolizumab plus axitinib over sunitinib monotherapy in treatment-naive, advanced renal cell carcinoma. The exploratory analysis with extended follow-up reported here aims to assess long-term efficacy and safety of pembrolizumab plus axitinib versus sunitinib monotherapy in patients with advanced renal cell carcinoma.
Axitinib plus immune checkpoint inhibitor: evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events. [2021]With the recent approval of the combinations of axitinib with the immune checkpoint inhibitor (ICI) pembrolizumab or avelumab for first-line treatment of advanced renal cell carcinoma, guidance on how to distinguish between immune-related adverse events (AEs) caused by ICI versus axitinib-related AEs is necessary to optimise therapy with axitinib-ICI combinations. The recommendations here are based on (1) systematic review of published evidence, (2) discussion among experts in the field and (3) a survey to obtain expert consensus on specific measures for therapy management with the combinations axitinib/avelumab and axitinib/pembrolizumab. The experts identified areas of AEs requiring unique management during treatment with axitinib-ICI combinations that were not covered by current recommendations. Diarrhoea, hepatic toxicity, fatigue and cardiovascular AEs were found to be applicable to such specialised management. Triage between immune-suppressive and supportive measures is a key component in therapy management. Clinical monitoring and experience with both classes of agents are necessary to manage this novel therapeutic approach. We focused on AEs with an overlap between axitinib and ICI therapy. Our recommendations address AE management of axitinib-ICI combinations with the aim to improve the safety of these therapies.
Characterization and Management of Treatment-emergent Hepatic Toxicity in Patients with Advanced Renal Cell Carcinoma Receiving First-line Pembrolizumab plus Axitinib. Results from the KEYNOTE-426 Trial. [2022]Pembrolizumab plus axitinib improved efficacy over sunitinib in treatment-naive advanced renal cell carcinoma in the KEYNOTE-426 (NCT02853331) study. However, a relatively high incidence of grade 3/4 aminotransferase elevations was observed.
Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. [2022]The combination of pembrolizumab and axitinib showed antitumor activity in a phase 1b trial involving patients with previously untreated advanced renal-cell carcinoma. Whether pembrolizumab plus axitinib would result in better outcomes than sunitinib in such patients was unclear.
Outcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma. [2023]Combination immune checkpoint inhibitors (ICI) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGF-R-TKI), including pembrolizumab/axitinib, are approved for first-line treatment of metastatic renal cell carcinoma (mRCC). Pembrolizumab/axitinib is associated with superior progression free survival (PFS), objective response rate (ORR), and overall survival over sunitinib. However, to date, the activity and safety of pembrolizumab/axitinib in later lines of therapy has not been reported.