Neoadjuvant Pembrolizumab and Axitinib in Renal Cell Carcinoma With Inferior Vena Cava Tumor Thrombus

NCT05969496 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-1669.cc
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Renal Cancer; Kidney Cancer; Renal Cell Carcinoma; Inferior Vena Cava Thrombosis

Outcome Measures

Primary Outcomes (2)

• 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

  baseline and 12 weeks

• 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.

  baseline and 12 weeks

Secondary Outcomes (4)

• Evaluate Surgical Complications after the Neoadjuvant Combination of Pembrolizumab and Axitinib Among Patients with RCC with IVC TT

  Date of surgery up to 30 days post operative or date of hospital discharge whichever occurs first

• Safety profile of the combination of Axitinib and Pembrolizumab

  baseline to 30 days post operative

• 1 year Progression Free Survival

  baseline, 3 months, 6 months, 9 months, 12 months from study enrollment

• 1 year Overall Survival

  12 months from study enrollment

Study Arms (1)

Combination Pembrolizumab and Axitinib

EXPERIMENTAL

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.

Drug: Axitinib; Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Pembrolizumab 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.

Also known as: Keytruda

Combination Pembrolizumab and Axitinib

Axitinib DRUG

Axitinib is a potent oral, vascular endothelial growth factor, c-kit and platelet derived growth factor inhibitor.

Also known as: Inlyta

Combination Pembrolizumab and Axitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Histologically proven clear cell component RCC.
• An upfront candidate for definitive surgery per treating Urologist.
• Suitable for and willing to undergo nephrectomy (either cytoreductive or with curative intent) per treating urologist.
• T Stage of any of the following: cT3b, cT3c, cT4
• N stage of any of the following: cN0 or cN1
• M stage of any of the following: cM0 or cM1
• ECOG performance status 0 - 2.
• Urinalysis \<2+ protein. If dipstick is ≥2+ then a 24-hour urine collection should be performed, and the patient may enter the trial if urinary protein is \<2g per 24 hours.
• All participants who have reproductive potential must have a negative serum or urine pregnancy test within a maximum of 14 days prior to starting trial treatment.
• Reproductive potential is defined as the following:
• Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
• Women \<50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
• Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \>1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy

You may not qualify if:

• 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).
• Has a history of severe hypersensitivity reaction (e.g., generalized rash/erythema, hypotension, bronchospasm, angioedema, or anaphylaxis) to Axitinib.
• Has a diagnosis of immunodeficiency OR is receiving a systemic steroid therapy greater than Prednisone 10 mg daily or a steroid equivalent, or any other form of immunosuppressive therapy within 7 days prior to enrollment to the study except in the case of central nervous system (CNS) metastases.
• Has an active autoimmune disease requiring systemic treatment within the past 2 years OR a documented history of clinically severe autoimmune disease. Note: Participants with vitiligo, Sjogren's syndrome, Type 1 diabetes, resolved childhood asthma/atopy, hypothyroidism or adrenal or pituitary insufficiency who are stable on hormone replacement are not excluded.
• Has a known additional malignancy that has progressed or has required active treatment in the last 3 years. Note: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ such as breast cancer in situ, thyroid cancer (papillary, hurthle cell or follicular), or localized prostate cancer are acceptable if they have undergone potentially curative therapy.
• Has known active CNS metastases and/or carcinomatous meningitis.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• ALT or AST above 3 times the upper limit of normal
• Has received a live virus vaccine within 30 days of enrollment to the study.
• Active GI bleeding, as evidenced by hematemesis, hematochezia, or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy.
• Intraluminal metastatic lesion with suspected bleeding, inflammatory bowel disease, ulcerative colitis or other GI condition associated with increased risk of perforation.
• Has QT interval corrected for heart rate (QTc) ≥480 msec.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Cancer League of Colorado: collaborator

Study Sites (3)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

RECRUITING

Hilands Ranch Hospital

Highlands Ranch, Colorado, 80129, United States

RECRUITING

Lone Tree Medical Center

Lone Tree, Colorado, 80124, United States

RECRUITING

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell

Interventions

Axitinib; pembrolizumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Elizabeth E Kessler, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew Lee

CONTACT

720-848-0630; matthew.lee@cuanscutz.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2023
• First Posted: August 1, 2023
• Study Start: December 4, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)