Neoadjuvant Lenvatinib and Pembrolizumab for IVC Tumor Thrombus

NCT05319015 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STU-2021-1240
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be evaluating safety and efficacy of the combination of lenvatinib and pembolizumab neoaadjuvant therapy prior to surgical resection of locally advanced renal cell carcinoma with IVC tumor thrombus.

Conditions

Renal Cell Carcinoma

Keywords

Renal Cell Carcinoma; IVC tumor thrombus; Neoadjuvant therapy; Immunotherapy; Nephrectomy

Outcome Measures

Primary Outcomes (3)

• Disease Control Rate

  Evaluation of changes in size of primary tumor and size and level of IVC tumor thrombus on imaging due to neoadjuvant therapy prior to surgery.

  12 weeks

• Local and Metastatic Progression Rate

  Evaluation of local or metastatic progression on imaging prior to surgery following neoadjuvant therapy.

  12 weeks

• 90 Day Post-Operative Complications

  Assessment of 90 day post-operative safety and morbidity of neoadjuvant therapy by evaluating the incidence of 90 day post-operative grade 3-5 adverse events.

  13 weeks

Secondary Outcomes (6)

• Estimated blood loss

  1 week

• Operative time

  1 week

• Length of stay

  1 week

• Intra-operative complications

  1 week

• Post-operative complications

  12 weeks

Other Outcomes (1)

• Exploratory Outcomes

  24 weeks

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Patients receive neoadjuvant lenvatinib (20 mg PO daily) for 12 weeks and pembrolizumab (200 mg IV every 3 weeks for four doses) prior to surgical resection of locally advanced RCC with IVC tumor thrombus. Following surgery, patients will receive adjuvant pembrolizumab (200 mg IV every 3 weeks for up to thirteen doses).

Drug: Neoadjuvant Lenvatinib; Drug: Neoadjuvant Pembrolizumab; Procedure: Radical nephrectomy, IVC thrombectomy, retroperitoneal lymph node dissection; Drug: Adjuvant Pembrolizumab

Interventions

Neoadjuvant Lenvatinib DRUG

20 mg PO daily for 12 weeks prior to surgery

Treatment Arm

Neoadjuvant Pembrolizumab DRUG

200 mg IV every 3 weeks for 4 doses prior to surgery

Treatment Arm

Radical nephrectomy, IVC thrombectomy, retroperitoneal lymph node dissection PROCEDURE

Resection of locally advanced RCC with IVC tumor thrombus

Treatment Arm

Adjuvant Pembrolizumab DRUG

200 mg IV every 3 weeks for up to 13 doses after surgery

Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent
• Have histologically confirmed cT3-4,N0-1,M0-1 (clinical stage III-IV) diagnosis of renal cell carcinoma (any subtype) with level II-IV inferior vena cava tumor thrombus as per the Mayo classification of macroscopic venous invasion in renal cell carcinoma:
• Level 1 tumor thrombus is either at the entry of renal vein or within the IVC \< 2 cm from the confluence of renal vein and IVC
• Level II tumor thrombus extends within the IVC \> 2 cm above the confluence of renal vein and IVC, but still remains below the hepatic veins.
• Level III tumor Thrombus involves the intrahepatic IVC.
• Level IV tumor thrombus extends above diaphragm or into the right atrium.
• The primary tumor and thrombus may be assessed to be resectable or unresectable at the time of enrollment.
• Male participants:
• A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the 120 day neoadjuvant treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants:
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents prior to allocation.
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. COVID-19 vaccines are permitted provided they are not live attenuated vaccines.
• 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 the first dose of study intervention with the exception of participating in the exploratory imaging trial utilizing 89Zr-DFO-Atezolizumab ImmunoPET/CT (STU-2019-0714).
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past year. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer, bladder in situ) that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Has more than three different sites of metastatic renal cell carcinoma.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and lenvatinib and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

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

Study Officials

• Vitaly Margulis, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Donna Mitchell

CONTACT

214-645-8787; donna.mitchell@utsouthwestern.edu

Doreen Simonsen

CONTACT

214-645-8790; doreen.simonsen@utsouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: March 23, 2022
• First Posted: April 8, 2022
• Study Start: January 6, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: August 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)