Overseen ByJad Chahoud, MD, MPH
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Must not be taking: Immunosuppressants, Steroids
Disqualifiers: Prior RCC therapy, Active infection, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a Phase II Clinical Trial that will evaluate the use of adaptive dosing of pembro-axi in patients with Metastatic Clear Cell Renal Cell Carcinoma (mccRCC).
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to stop them at least 7 days before starting the trial.
What data supports the effectiveness of the drug combination Pembrolizumab and Axitinib for kidney cancer?
Research shows that Pembrolizumab and Axitinib together have a 73% response rate in treating advanced kidney cancer that hasn't been treated before. This combination is now considered a standard treatment for kidney cancer that has spread beyond the kidney.
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 common side effects include diarrhea, liver issues, fatigue, and heart-related problems. Careful monitoring and management are important to handle these side effects.
13567How is the drug pembrolizumab plus axitinib unique for kidney cancer treatment?
Pembrolizumab plus axitinib is unique because it combines an immune checkpoint inhibitor (pembrolizumab) with a targeted therapy (axitinib) to treat advanced kidney cancer, offering improved efficacy over the traditional drug sunitinib, and is now a standard first-line treatment for patients whose cancer has spread beyond the kidney.
12458Eligibility Criteria
Adults with advanced kidney cancer (mccRCC) who haven't had systemic therapy for it can join this trial. They need to be fairly healthy, able to perform daily activities, and have a tumor that can be measured. People with well-controlled HIV or hepatitis are okay if they use contraception. Those with recent heart issues, uncontrolled infections or blood pressure, severe allergies to the drugs being tested, other active cancers, or major health events like surgery recently cannot participate.Inclusion Criteria
I am 18 years old or older.
I have been active and able to care for myself within the last 28 days.
I can provide a sample of my tumor or am willing to have a biopsy.
+8 more
Exclusion Criteria
I haven't taken high doses of steroids or have an immunodeficiency within the last week.
I haven't had heart problems in the last 6 months.
I do not have uncontrolled HIV, Hepatitis B, or Hepatitis C.
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive adaptive dosing of pembro-axi, with pembrolizumab given at 200 mg IV every 3 weeks and axitinib 5 mg orally twice daily. Imaging is conducted every 9 weeks to assess response.
9 weeks
3 visits (in-person) for pembrolizumab administration, imaging every 9 weeks
Adaptive Therapy
Therapy cycles on and off based on tumor response, continuing until confirmed progression of disease.
Up to 36 months
Follow-up
Participants are monitored for safety and effectiveness after treatment, with a focus on progression-free survival and overall survival.
Up to 12 months
Participant Groups
The study is testing how well patients respond when given Pembrolizumab and Axitinib in varying doses for advanced kidney cancer (mccRCC). It's a Phase II trial which means they're looking at effectiveness and side effects of these drugs after seeing some safety data from earlier studies.
1Treatment groups
Experimental Treatment
Group I: Adaptive Dosing pembro-axiExperimental Treatment2 Interventions
In therapy naïve mccRCC patients, a standard dose of pembrolizumb will be given at 200 mg iv every 3 weeks, with axitinib given orally 5 mg twice daily.
After 9 weeks, subjects will undergo the first response assessment as well as the therapy portion of the trial if they have 20% response per RECIST criteria.
During adaptive dosing with pembro-axi, imaging is conducted every 9 weeks. Treatment is held until the tumor has returned to its baseline size or greater per RECIST 1.1, then restarted until a tumor reduction of at least 20% occurs.
Therapy cycles on and off in this manner continue as the tumor shrinks and grows until confirmed progression of disease while on therapy.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
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Who Is Running the Clinical Trial?
H. Lee Moffitt Cancer Center and Research InstituteLead Sponsor
References
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.
Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibition Is the New Backbone in First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma. [2020]Recent randomised trials have demonstrated a survival benefit for a front-line ipilimumab and nivolumab combination therapy, and pembrolizumab and axitinib combination therapy in metastatic clear-cell renal cell carcinoma. The European Association of Urology Guidelines Panel has updated its recommendations based on these studies. PATIENT SUMMARY: Pembrolizumab plus axitinib is a new standard of care for patients diagnosed with kidney cancer spread outside the kidney and who did not receive any prior treatment for their cancer (treatment naïve). This applies to all risk groups as determined by the International Metastatic Renal Cell Carcinoma Database Consortium criteria.
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 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.
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).
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.
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.