Consolidative Metastasis and Primary Directed Therapy (MPDT) for Renal Cell Carcinoma (RCC)

A Phase II Study of Total Consolidative Metastasis-and-primary Directed Therapy (MPDT) for Renal Cell Carcinoma (RCC).

This is a non-randomized, open-label phase II study designed to estimate 12-month treatment-free survival rate following total consolidative metastasis-and-primary directed therapy (MPDT) among patients with partial response/stable disease after at least 6 months of immune checkpoint blockade-based therapy for metastatic clear cell RCC. The investigators hypothesize that patients who undergo total consolidative MPDT followed by systemic therapy discontinuation will have a 12-month treatment-free survival rate of 32% compared to a null hypothesis of 13%

Study Overview

• Status: Not yet recruiting
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Procedure: Total consolidative MPDT

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Matthew Doyle; Phone Number: 610-357-6354; Email: Matthew.Doyle@Pennmedicine.upenn.edu
• Study Contact Backup: Name: Naomi Haas, MD; Phone Number: 2156627615; Email: Naomi.Haas@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center at University of Pennsylvania
      • Contact: Matthew Doyle; Phone Number: 610-357-6354; Email: Matthew.Doyle@Pennmedicine.upenn.edu
      • Contact: Naomi Haas; Phone Number: 215-662-7615; Email: Naomi.Haas@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of clear cell renal cell carcinoma (mixed histology acceptable but must have clear cell component)
• Metastatic clear cell RCC with 5 or fewer metastases at enrollment (excluding pulmonary nodules <1.0cm)
• Stable disease or partial response as assessed by investigators following at least 6 months of immune checkpoint blockade-based therapy.
• Has disease amenable for total consolidative focal therapy (this will be determined by a multidisciplinary team which may include a combination of medical oncologists, urologists, interventional radiologists, and radiation oncologists).
• ECOG performance status < 2
• Must have archival tissue (slide or Formalin-Fixed Paraffin-Embedded tissue) preceding prior systemic treatment for comparison to tissue from consolidation
• Consolidation surgery and biopsies are strongly encouraged to be within 42 days +/- 7 days of holding systemic therapy.

Exclusion Criteria:

• Subjects who have progressed during the first 6 months of immune checkpoint-blockade based therapy as determined by study investigator.
• Subjects who have a need for urgent focally directed therapy (i.e. symptomatic brain or spinal metastases). Stable spinal metastases resected and/or treated with SBRT in advance of or concurrently with immune checkpoint-blockade based therapy are allowed to participate.
• Any female of child-bearing potential who has a positive urine pregnancy test within 72 hours before screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Participants must be excluded/discontinued from the trial in the event of a positive or borderline positive serum pregnancy test result.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Total consolidative MPDT; Participants will discontinue systemic anti-cancer therapy for metastatic RCC, and standard of care definitive procedures or metastatic RCC. These procedures include one or more of the following: surgery (e.g. nephrectomy, metastasectomy, lymph node dissection), percutaneous cryoablation and/or radiotherapy (SAbR or other definitive radiotherapy).	Procedure: Total consolidative MPDT; After stopping systemic anti-cancer therapy for metastatic RCC, participant will receive one or more of the following: surgery (e.g. nephrectomy, metastasectomy, lymph node dissection), percutaneous cryoablation and/or radiotherapy (SAbR or other definitive radiotherapy).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-free survival	Treatment-free survival, defined as the time from discontinuation of anti-cancer therapy until either: 1) the resumption of systemic therapy; 2) the first date of additional focally-directed therapy; or 3) death.	From discontinuation of anti-cancer therapy until resumption of systemic therapy, first date of additional focally-directed therapy or death, whichever comes first, assessed up to 60 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival	Recurrence-free survival, defined as the time from completion of total consolidative MPDT until investigator-assessed disease recurrence.	From completion of total consolidative MPDT until investigator-assessed disease recurrence, assessed up to 60 months..
Grade 3 or higher adverse events	Grade 3 or higher adverse events according to the Clavien-Dindo scale (surgery), Society for Interventional Radiology scale (percutaneous cryoablation), or the CTCAE v5.0 (radiotherapy)	From completion of total consolidative MPDT until investigator-assessed disease recurrence, assessed up to 60 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify an immune signature that correlates with treatment free survival	The investigators will broadly interrogate immune cell types from the peripheral blood and tumor tissue	At week 6 and week 12 following systemic therapy initiation, at the time of study enrollment and following total consolidative MPDT, through study completion, estimated to be 36 months.

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Investigators: Principal Investigator: Naomi Haas, MD, Penn Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): April 11, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: December 23, 2024
• First Submitted That Met QC Criteria: January 7, 2025
• First Posted (Actual): January 13, 2025

Study Record Updates

• Last Update Posted (Actual): January 9, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell
• Other Study ID Numbers: UPCC 33824; IRB#857362 (Other Identifier: [University of Pennsylvania IRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No