Neoadjuvant Pembrolizumab and Axitinib in Renal Cell Carcinoma With Inferior Vena Cava Tumor Thrombus
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Colorado, Denver
About 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Provision to sign and date the consent form.
Stated willingness to comply with all study procedures and be available for the duration of the study.
Participant self-identified gender ages >/= 18 years old is acceptable and appropriate if they meet other inclusion criteria.
Histologically proven clear cell component RCC.
Disqualifiers
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to enrollment.
Has had major surgery within 4 weeks or received radiation therapy within 1 week prior to enrollment to the study.
Has had prior treatment with any anti-programmed cell death (anti-PD-1) or programmed cell death ligand 1 (PD-L1), or an antibody targeting any other immune-regulatory receptors or mechanisms.
Has received prior systemic anti-cancer therapy for RCC with vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFR).
Trial design
Design model
Single group
Treatments tested in this trial
Axitinib
DrugAxitinib is a potent oral, vascular endothelial growth factor, c-kit and platelet derived growth factor inhibitor.
Pembrolizumab
DrugPembrolizumab is a type of immunotherapy. It stimulates the body's immune system to fight cancer cells. Pembrolizumab targets and blocks a protein called PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 triggers the T-cells to find and kill cancer cells.
Treatment groups
17 Participants
are divided into 1 treatment groupGroup A: Combination Pembrolizumab and AxitinibExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Evaluate Change in IVC Tumor Thrombus Extent Based on the Mayo Classification
* Patients will get baseline imaging with an MRI of the abdomen to evaluate the level of the IVC TT based on the Mayo Classification. Patients will get an end of treatment MRI at 12 weeks to evaluate the efficacy of neoadjuvant therapy with Pembrolizumab and Axitinib. The Mayo classification is described as below: * Level 0: thrombus limited to the renal vein * Level 1: into IVC \<2cm from renal vein ostium level * Level 2: IVC extension \>2cm from renal vein ostium and below hepatic vein * Level 3: thrombus at the level of or above the hepatic veins but below the diaphragm * Level 4: thrombus extending above the diaphragm
Time frame
baseline and 12 weeks2
Evaluate a change in IVC TT Size from Baseline
o Evaluation of IVC TT anteroposterior and transverse diameter will also be measured at baseline and the end of treatment at 12 weeks. The baseline largest diameter will be subtracted to the largest diameter as the end of treatment divided by the baseline largest diameter will be computed to evaluate the percentage change in the IVC TT size.
Time frame
baseline and 12 weeksSecondary outcomes
1
Evaluate Surgical Complications after the Neoadjuvant Combination of Pembrolizumab and Axitinib Among Patients with RCC with IVC TT
* Surgical morbidity will be graded based on the Clavien- Dindo Classification. This will be graded as below: * Grade I: Any deviation from the normal post-operative course not requiring surgical, endoscopic, or radiological intervention (inc. certain drugs, physiotherapy and wound infections that are opened at the bedside) * Grade II: Complications requiring drug treatments other than those allowed for Grade I complications (inc. blood transfusion and total parenteral nutrition (TPN)) * Grade III: Complications requiring surgical, endoscopic, or radiological intervention (IIIa=not under general anesthetic/IIIb=under general anesthetic) * Grade IV: Life-threatening complications (inc. CNS complications requiring intensive care, but excludes transient ischemic attacks (TIAs)) (IVa=single-organ dysfunction (inc. dialysis)/IVb=multi-organ dysfunction) * Grade V: Death of the patient
Time frame
Date of surgery up to 30 days post operative or date of hospital discharge whichever occurs first2
Safety profile of the combination of Axitinib and Pembrolizumab
Catalogue o Any grade adverse event o Grade 3 or higher adverse event possibly, probably, or definitely related to study therapy All treatment related adverse events will be assessed using the Common Terminology Criteria for Adverse Events v5.0
Time frame
baseline to 30 days post operative3
1 year Progression Free Survival
Progression-free survival is defined as any clinical or radiographic progression or death from any cause one year after enrollment in the study
Time frame
baseline, 3 months, 6 months, 9 months, 12 months from study enrollment4
1 year Overall Survival
One year- Overall survival. Overall survival is defined as death from any cause one year after enrollment in the study
Time frame
12 months from study enrollmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Colorado, Denver
Lead sponsor
Cancer League of Colorado
Collaborator
Source ClinicalTrials.gov