PET/CT-guided treatment break for metastatic kidney cancer with favorable or intermediate IMDC risk

An Open-label, Investigator-initiated, Single Arm, Exploratory Phase 2 Trial Evaluating the Feasibility and Efficiency of PET/CT Directed Free of Therapy Used for Metastatic and Advanced Renal Cell Carcinoma

This trial tries using PET/CT scans to guide temporary treatment breaks for people with metastatic kidney cancer (IMDC favorable or intermediate risk) who have had at least 12 months of combined PD-1/PD-L1 immunotherapy plus a VEGFR TKI and show a metabolic response.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jinling Hospital, China (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT07175480 on ClinicalTrials.gov

What this trial studies

Most first-line therapy for metastatic renal cell carcinoma combines immune checkpoint inhibitors with VEGFR-targeted TKIs, but continuous treatment can cause cumulative toxicity and high cost. This phase 2, single-center protocol uses PET/CT metabolic response (PERCIST) after a minimum 12 months of ICI+TKI to select patients with complete or partial metabolic responses for a planned treatment holiday. Eligible patients enter a monitored break off both agents with serial imaging and clinical follow-up to watch for recurrence and safety signals. The trial's primary focus is feasibility and efficiency of PET/CT-directed treatment interruption, with exploratory endpoints including time off therapy, progression patterns, and safety.

Who should consider this trial

Good fit: Adults (≥18) with unresectable or metastatic RCC who are IMDC favorable or intermediate risk, ECOG 0–1, have completed ≥12 months of first-line PD-1/PD-L1 plus VEGFR-TKI therapy, and achieve complete or partial metabolic response on PET/CT within 24 months.

Not a fit: Patients with poor IMDC risk, short induction (<12 months), persistent metabolic activity on PET/CT, poor performance status, or those unable to undergo close imaging follow-up are unlikely to benefit from a PET/CT-directed treatment pause.

Why it matters

Potential benefit: If successful, this approach could allow some patients to safely pause systemic therapy, reducing side effects and financial burden while preserving disease control.

How similar studies have performed: Intermittent or treatment-free interval strategies have shown promise in some cancers and in limited RCC settings, but PET/CT-directed treatment pauses based on metabolic response are relatively novel and not yet validated in large trials.

Eligibility criteria

Pre-screening Inclusion Criteria:

1. Male or female subjects aged ≥ 18 years at time of signing informed consent
2. Locally advanced (not amenable to curative surgery or radiation therapy) or metastatic RCC (American Joint Committee on Cancer \[AJCC\] Stage IV)
3. Favorable or intermediate risk as per International Metastatic RCC Database Consortium (IMDC) criteria
4. Eastern Cooperative Oncology Group performance status 0 or 1
5. Karnofsky Performance Status (KPS) grade ≥ 70%
6. Adequate organ and bone marrow function meeting all laboratory criteria:

   Ⅰ. Absolute neutrophil count (ANC) ≥ 1.5 × 10³/μL (≥ 1.5 GI/L); Platelet count ≥ 100 × 10³/μL (≥ 100 GI/L); Hemoglobin ≥ 9 g/dL (≥ 90 g/L)

   Ⅱ. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 × upper limit of normal. Total bilirubin ≤ 1.5 × the upper limit of normal (≤ 3 mg/dL \[≤ 51.3 μmol/L\] if Gilbert's syndrome)

   Ⅲ. Serum creatinine ≤ 2.0 × upper limit of normal or calculated creatinine clearance ≥ 30 mL/min using the Cockroft-Gault formula.
7. Capacity to comprehend and comply with protocol requirements, with documented informed consent signed
8. Contraception agreement for sexually active fertile participants and partners to use of medically accepted methods during study and continue for 5 months after last treatment
9. Negative pregnancy status at screening for women of childbearing potential

Pre-screening Exclusion Criteria:

1. Highly malignant pathology
2. Prior systemic therapy for advanced RCC
3. Poor risk as per International Metastatic RCC Database Consortium (IMDC) criteria
4. ECOG performance status \>1
5. Karnofsky Performance Status (KPS) \<70%
6. Inadequate organ and bone marrow function
7. Bulky or symptomatic disease or hepatic metastases
8. Active brain metastases or leptomeningeal disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before the start of treatment.
9. Concurrent or prior invasive malignancies that could confound efficacy assessment, except adequately treated non-melanoma skin cancer, superficial bladder cancer or carcinoma in situ of the cervix/breast with curative therapy \>3 years ago.
10. Uncontrolled hypertension (\>150/100 mmHg despite optimal therapy)
11. Uncontrolled comorbidities within 6 months including but not limited to: clinically significant cardiovascular disorders, gastrointestinal disorders with high risk of perforation or fistula formation, significant hematuria, hematemesis, hemoptysis, or major bleeding history, severe infections, severe autoimmune diseases (e.g., systemic lupus erythematosus, immune pneumonitis), active HIV, HBV, or HCV infections.
12. Major surgery within 4 weeks with unhealed wounds or planned surgery during study
13. Concomitant use of drugs or substances affecting activity or pharmacokinetics of investigational products
14. Hypersensitivity to any component of study drugs
15. Chronic or concurrent immunosuppressive therapy, except Inhaled/topical steroids
16. Medical/psychiatric/social conditions compromising protocol compliance
17. Pregnancy, lactation, or refusal of contraception during and for 5 months post-treatment
18. Inability to undergo PET/CT or oral drug administration

Main-screening Inclusion Criteria:

1. Patient must receive≥12 months of first line treatment with the combination of PD-1/PD-L1 ICI and VEGFR-TKI, and have not experienced a toxicity that prevents them from continuing on therapy.
2. Patients must achieve complete metabolic response (CMR) or partial metabolic response (PMR) on PET/CT within 24 months of the combination treatment with PD-1/PD-L1 ICI and VEGFR-TKI.
3. Favorable or intermediate risk as per International Metastatic RCC Database Consortium (IMDC) criteria
4. Eastern Cooperative Oncology Group performance status 0 or 1
5. Karnofsky Performance Status (KPS) grade ≥ 70%
6. Adequate organ and bone marrow function meeting all laboratory criteria:

   Ⅰ. Absolute neutrophil count (ANC) ≥ 1.5 × 10³/μL (≥ 1.5 GI/L); Platelet count ≥ 100 × 10³/μL (≥ 100 GI/L); Hemoglobin ≥ 9 g/dL (≥ 90 g/L)

   Ⅱ. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 × upper limit of normal. Total bilirubin ≤ 1.5 × the upper limit of normal (≤ 3 mg/dL \[≤ 51.3 μmol/L\] if Gilbert's syndrome)

   Ⅲ. Serum creatinine ≤ 2.0 × upper limit of normal or calculated creatinine clearance ≥ 30 mL/min using the Cockroft-Gault formula.
7. Capacity to comprehend and comply with protocol requirements, with documented informed consent signed
8. Contraception agreement for sexually active fertile participants and partners to use of medically accepted methods during study and continue for 5 months after last treatment
9. Negative pregnancy status at screening for women of childbearing potential

Main-screening Exclusion Criteria:

1. Failure to complete ≥12 months of first-line PD-1/PD-L1 + VEGFR-TKI therapy due to unmanageable toxicity or other reasons
2. Failure to achieve CMR or PMR on PET/CT within 24 months after combination therapy; new metastatic lesions or disease progression on PET/CT.
3. Poor risk as per International Metastatic RCC Database Consortium (IMDC) criteria
4. ECOG performance status \>1
5. Karnofsky Performance Status (KPS) \<70%
6. Inadequate organ and bone marrow function
7. Uncontrolled hypertension (\>150/100 mmHg despite optimal therapy)
8. Uncontrolled comorbidities including but not limited to: clinically significant cardiovascular disorders, gastrointestinal disorders with high risk of perforation or fistula formation, significant hematuria, hematemesis, hemoptysis, or major bleeding history, severe infections, severe autoimmune diseases (e.g., systemic lupus erythematosus, immune pneumonitis), active HIV, HBV, or HCV infections.
9. Medical/psychiatric/social conditions compromising protocol compliance
10. Pregnancy, lactation, or refusal of contraception during study period.
11. Inability to undergo PET/CT or oral drug administration

Withdrawal Criteria:

1. Disease progression with unsatisfactory efficacy, or occurrence of intercurrent illnesses during treatment or follow-up period.
2. Occurrence of severe treatment-related adverse reactions.
3. Laboratory test results indicating critical safety values.
4. Voluntary withdrawal of informed consent by the patient.
5. Investigator's judgment that withdrawal is in the subject's best interest.
6. Pregnancy during the trial period.
7. Wrong Enrollees: deviation of inclusion or exclusion criteria.
8. Poor patient compliance.
9. Loss to follow-up or death during the trial period.

Where this trial is running

Nanjing, Jiangsu

• Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China — Nanjing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Le Qu, M.D

Conditions Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma