Pembrolizumab Plus Lenvatinib in Stage III-IV RCC

Phase 2

Recruiting

• Conditions: Renal Cell Carcinoma
• Interventions: Drug: Pembrolizumab plus Lenvatinib

• Registration Number: NCT05485896
• Lead Sponsor: Tianjin Medical University Second Hospital

Brief Summary

This is a phase II study to determine the efficacy and safety of Pembrolizumab when given in combination with Lenvatinib as treatment for patients with the advanced kidney cancer. Further evaluate whether the treatment plan is beneficial to the patient's operation. Patients will receive treatment with Pembrolizumab in combination with Lenvatinib every 3 weeks for 3 cycles pre-operation and patients need to continue taking the drug for a year after surgery.

Detailed Description

This is a phase II study to determine the efficacy and safety of Pembrolizumab when given in combination with Lenvatinib as treatment for patients with the advanced kidney cancer . Further evaluate whether the treatment plan is beneficial to the patient's operation.Patients will receive treatment with Pembrolizumab in combination with Lenvatinib every 3 weeks for 3 cycles pre-operation and patients need to continue taking the drug for a year after surgery. The main objective of the study was to evaluate whether the treatment was beneficial to patients undergoing surgery.

Study Timeline

• Study Start: 2022-07-01
• Study First Submitted: 2022-07-25
• Status Verified: 2022-08
• Study First Submitted QC: 2022-08-02
• Study First Posted: 2022-08-03
• Last Update Submitted: 2022-08-04
• Last Update Posted: 2022-08-08
• Primary Completion: 2023-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Willing and able to provide written informed consent

2. Age ≥ 18 years and age ≤75years

3. Patients with pathologically and radiographically confirmed renal cell carcinoma: Clinical staging:cT3N0-1M0-1,cT4N0-1M0-1(III/IV stage)

4. Preoperative imaging evaluation can be performed radical excision or tumor reduction surgery

5. There are no suspected brain metastases

6. The presence of measurable lesions was assessed according to RECISTv1.1 criteria

7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

8. Organ function level must meet the following requirements:

   Hematological indexes: neutrophil count >= 1.5x10^9/L, platelet count >= 100x10^9/L, hemoglobin >= 9.0 g/dl (can be maintained by blood transfusion); Liver function: total bilirubin <=1.5 ULN, alanine aminotransferase and aspartate aminotransferase <=1.5 ULN

9. Women were required to use an effective contraceptive method for three months after the end of the study, and men were required to consent to use an effective contraceptive method with their spouse during and for three months after the end of the study

10. The subjects volunteered to join the study, signed informed consent, and had good compliance with follow-up

Exclusion Criteria

1. Prior treatment with radiation, chemotherapy, long-term or high-dose hormone therapy, or immune checkpoint inhibitors
2. Previous or concurrent other malignancy
3. Previous PD-L1 or PD-L1 treatment, or allergy to PD-L1
4. History of primary immunodeficiency
5. Active, known or suspected autoimmune diseases
6. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
7. Pregnant or lactating female patients;
8. Untreated acute or chronic active hepatitis B or hepatitis C infection. Under the condition of monitoring the virus copy number of patients receiving antiviral treatment, doctors can judge whether they are in line with the patients' individual conditions;
9. Have a clear history of active tuberculosis;
10. Participating in other clinical researchers;
11. Men with reproductive capacity or women who are likely to become pregnant do not take reliable contraceptive measures;
12. Uncontrolled concurrent diseases, including but not limited to:

HIV infected (HIV antibody positive); Severe infection in active stage or poorly controlled; Evidence of serious or uncontrollable systemic diseases (such as severe mental, neurological, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver or kidney diseases, uncontrolled hypertension [i.e. hypertension greater than or equal to CTCAE grade 2 after drug treatment]); Patients with active bleeding or new thrombotic disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Advanced RCC (Locally advanced, regional LN invaded, or M1-NED)	Pembrolizumab plus Lenvatinib	Patients will receive treatment with Pembrolizumab in combination with Lenvatinib every 3 weeks for 3 cycles in the preoperation. In addition, 17 cycles' Pembrolizumab were needed for patients with high risk of recurrence (tumor stage 2 with nuclear grade IV or sarcomatoid differentiation, tumor stage 3 or higher, regional lymph-node metastasis, or stage M1 with no evidence of disease residual).

Primary Outcome Measures

Name	Time	Method
Tumor responses	Through treatment completion (before surgery), an average of 3 cycles (each cycle is 21 days).	All patients had imaging (enhanced CT, enhanced MRI or both ) before and after treatment to evaluate radiographic response within the primary tumor and venous tumor thrombus by using RECIST (Response Evaluation Criteria in Solid Tumors)
Adverse events	Through treatment completion (before surgery), an average of 3 cycles (each cycle is 21 days).	Adverse events were monitored throughout treatment until 30 days after surgery and were evaluated according to Common Terminology Criteria for Adverse Events (version 5.0).

Secondary Outcome Measures

Name	Time	Method
Progression free survival	Every 12 weeks until 12 months after surgery	Progression free survival was assessed by imaging (enhanced CT, enhanced MRI or both ) after surgery every 12 weeks until 12 months.
Tumor viability assessment	Through treatment completion (before surgery), an average of 3 cycles (each cycle is 21 days).	Densitometric measurement of tumor viability using a modification of the Choi criteria was performed to evaluate the effect. Briefly, using axial source computed tomography images (1.5 mm thickness) a three-dimensional image of the kidney was reconstructed with an imaging workstation (Terra Recon, San Mateo, CA).

Trial Locations

Locations (1)

Changyi Quan; 🇨🇳 Tianjin, Tianjin, China