Efficacy and Safety of Fruquintinib in Combination With Sintilimab in Advanced Renal Cell Carcinoma (FRUSICA-2)

Advanced Renal Cell Carcinoma Clinical Trial

Official title:

A Phase II/III Clinical Study to Evaluate the Efficacy and Safety of Fruquintinib in Combination With Sintilimab Versus Axitinib or Everolimus as Second-line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (FRUSICA-2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05522231
• Other study ID #: 2022-013-00CH1
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: October 27, 2022
• Est. completion date: March 2025

Study information

• Verified date: March 2024
• Source: Hutchmed
• Contact: Yu Wang
• Phone: 18058125909
• Email: yuwang[@]hutch-med.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study consists of two parts, the first part is a randomized, open-label, active-controlled study to evaluate the efficacy and safety of fruquintinib in combination with sintilimab versus axitinib or everolimus montherapy as second-line treatment for locally advanced or metastatic renal cell carcinoma. The second part is a fruquintinib montherapy factorial cohort study to evaluate the efficacy and safety of fruquintinib monotherapy as for second-line treatment of locally advanced or metastatic renal cell carcinoma.

Description:

The target populations for this study were patients with histologically or cytologically confirmed, locally advanced/ metastatic renal cell carcinoma who progressed during or after or intolerant to previous first-line VEGFR-TKI therapy.

A total of about 249-264 patients are planned to be enrolled in the study, among whom about 234 patients are planned to be enrolled in the first part. The patients who are successfully enrolled will be randomly assigned into the investigational arm or the control arm in a 1:1 ratio. The enrollment of part 2 will be started after that of part 1 is completed. About 15~30 patients are planned to be enrolled in the second part. The patients who are successfully enrolled will receive fruquintinib monotherapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 264
• Est. completion date: March 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. 18 to 75 (inclusive) years of age on the date when ICF was signed;

2. Histologically or cytologically confirmed renal clear cell carcinoma;

3. Patients with locally advanced/metastatic renal carcinoma;

4. Patients with renal carcinoma who progressed during or after or intolerant to previous first-line VEGFR-TKI therapy for advanced/metastatic disease;

5. At least 1 measurable lesion according to RECIST 1.1;

6. ECOG PS of 0 or 1;

7. Adequate organ function.

Exclusion Criteria:

1. Had previously received therapy targeting immune modulatory receptors or related pathways (including but not limited to therapy targeting PD-1, CTLA-4, IDO, PD-L1, LAG-3, TIGIT, IL-2R and GITR, etc, but excluding related cytokine therapy such as IL2), excluding patients who had received immunotherapy such as anti-PD- (L) 1 antibody in adjuvant/neoadjuvant therapy setting and did not progress within 6 months after discontinuation;

2. Receiving approved systemic anti-tumor therapy within 2 weeks prior to the first dose;

3. Toxicities caused by prior anti-tumor therapy before the first dose that did not recover to Grade 0 or 1 per the NCI CTCAE v5.0 or to the level specified in the enrollment criteria (excluding alopecia and peripheral neurotoxicity = CTCAE Grade 2);

4. Immunosuppression medication within 4 weeks prior to randomization;

5. Patients with active autoimmune or inflammatory diseases;

6. Known central nervous system (CNS) metastasis;

7. History of pneumonitis requiring corticosteroid therapy, or history of or current interstitial lung disease, or current active pulmonary infection, etc.;

8. Toxicities caused by prior anti-tumor therapy before the first dose that did not recover to Grade 0 or 1 per the National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) v5.0 or to the level specified in the enrollment criteria (excluding alopecia and peripheral neurotoxicities =CTCAE Grade 2 caused by platinum-based chemotherapy; thyroid dysfunction with stable disease control after symptomatic treatment);

9. Human Immunodeficiency Virus (HIV) Infection (HIV 1/2 Antibody positive);

10. Uncontrolled hypertension despite standard therapy;

11. Patient with evidence or history of haemorrhagic tendency within 2 months prior to the first dose, regardless of severity.

Related Conditions & MeSH terms

• Advanced Renal Cell Carcinoma
• Carcinoma
• Carcinoma, Renal Cell

Intervention

Drug:
• fruquintinib+sintilimab
fruquintinib, 5 mg, QD, PO, 2 weeks on/1 week off, 3 weeks/cycle; sintilimab, 200 mg, IV infusion, Q3W, 3 weeks/cycle.
• axitinib / everolimus
axitinib, 5 mg, twice daily (BID), PO, 3 weeks/cycle, dose escalation will be at the investigator 's discretion based on clinical; everolimus, 10 mg, QD, PO, 3 weeks/cycle.
• fruquintinib
fruquintinib, 5 mg, QD, PO, 3 weeks on/ 1 week off, 4 weeks/cycle.

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Hutchison Medipharma Limited

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival (PFS) in Part I	PFS per RECIST 1.1 by BIRC	Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
Primary	Objective response rate (ORR) in Part II	ORR per RECIST 1.1 by investigator	Time from the date of first treatment administration until disease progression or the introduction of a new treatment, assessed up to 20 months.
Secondary	PFS	PFS per RECIST 1.1	Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
Secondary	Safety in Part I	Severity and Incidence of Adverse event (AEs) and findings in Laboratory test, vital signs, 12-lead Electrocardiogram (ECG), etc. in Part I	Through study completion, assessed up to 20 months.
Secondary	Quality of life in Part I	Quality of life Questionnare analysis in Part I	Through study completion, assessed up to 20 months.
Secondary	Safety in Part II	Severity and incidence of AEs and findings in such as Laboratory test, vital signs, 12-lead ECG, etc. in Part II.	Through study completion, assessed up to 20 months.
Secondary	Disease control rate (DCR)	PFS per RECIST 1.1	Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
Secondary	ORR	ORR per RECIST 1.1	Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
Secondary	Duration of response (DoR)	DoR per RECIST 1.1	Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
Secondary	Time to Response (TTR)	TTR per RECIST 1.1	Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
Secondary	OS	OS	Time from date of randomization until the date of death from any cause, assessed up to 20 months.