Clinical trial NCT05522231: Efficacy and Safety of Fruquintinib in Combination With Sintilimab in Advanced Renal Cell Carcinoma (FRUSICA-2)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Advanced Renal Cell Carcinoma
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2022-08-30
Enrollment: 265
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 monotherapy as second-line treatment for locally advanced or metastatic renal cell carcinoma. The second part is a fruquintinib monotherapy 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression free survival (PFS) in Part I
timeFrame: 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.
measure: Objective response rate (ORR) in Part II
timeFrame: Time from the date of first treatment administration until disease progression or the introduction of a new treatment, assessed up to 20 months.
Secondary outcomes:
measure: PFS
timeFrame: 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.
measure: Safety in Part I
timeFrame: Through study completion, assessed up to 20 months.
measure: Quality of life in Part I
timeFrame: Through study completion, assessed up to 20 months.
measure: Safety in Part II
timeFrame: Through study completion, assessed up to 20 months.
measure: Disease control rate (DCR)
timeFrame: 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.
measure: ORR
timeFrame: 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.
measure: Duration of response (DoR)
timeFrame: 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.
measure: Time to Response (TTR)
timeFrame: 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.
measure: OS
timeFrame: Time from date of randomization until the date of death from any cause, assessed up to 20 months.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital, Capital Medical University
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Changsha
country: China
facility: Xiangya Hospital Central South University
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
city: Fuzhou
country: China
facility: The First Affilated Hospital of Fujian Medical University
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
city: Ha'erbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University
city: Hefei
country: China
facility: Anhui Provincial Hospital
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
city: Jinan
country: China
facility: Shandong Cancer Hospital & Institute
city: Kunming
country: China
facility: Yunnan Cancer Hospital
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
city: Nantong
country: China
facility: Nantong Tumor Hospital
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Renji Hospital,Shanghai Jiaotong University School of Medicine
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
city: Shanghai
country: China
facility: Shanghai General Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institution
city: Shenyang
country: China
facility: The First Hospital of China Medical University
city: Tianjin
country: China
facility: The Second Hospital of Tianjin Medical University
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou medical university
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical College of HUST
city: Wuhan
country: China
facility: Wuhan Union Hospital of China
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hosiptal)
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
Study officials:
affiliation: Fudan University
name: Dingwei Ye
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking University First Hospital
name: Zhi Song He
role: PRINCIPAL_INVESTIGATOR
References: