Fruquintinib Plus Everolimus as 2nd Line Therapy of ccRCC Patients Progressed Post IO and TKI Therapy

NCT06317298 | Recruiting

• 1 other identifier: 2023-013-CH01 IIT-RCC
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess the efficacy and safety profile of fruquintinib in combination with everolimus as second line therapy of clear cell renal cell carcinoma patients who progressed after immunotherapy and tyrosine kinase inhibitor.

Conditions

Renal Cell Carcinoma, Clear Cell, Somatic

Keywords

fruquintinib; everolimus

Outcome Measures

Primary Outcomes (2)

• MTD (Maximum Tolerated Dose)

  the maximum dose in which the proportion of patients who experience dose limited toxicity (DLT) within 28 days after the first dose level is less than or equal to 1/6. When DLT occurs in patients with a dose level greater than 1/6, a dose level lower than this dose level is considered MTD. The MTD dose group requires at least 6 DLT evaluable patients to be confirmed.

  6 month

• ORR (Objective Response Rate)

  Based on the evaluable set of tumor efficacy, it is defined as the sum of the proportions of patients with confirmed complete response (CR) or partial response (PR) as the best overall evaluation per RECIST(Response Evaluation Criteria In Solid Tumors )1.1criteria

  1 year

Secondary Outcomes (2)

• PFS (Progression Free Survival)

  1 year

• DCR (Decease Control Rate )

  1 year

Study Arms (3)

Fruquintinib(3mg) plus Everolimus

EXPERIMENTAL

Fruquintinib 3mg Qd 21 days on 7 days off; Everolimus 5mg Qd; 28 day cycle until disease progression or intolerable adverse events

Drug: Fruquintinib and Everolimus

Fruquintinib(4mg) plus Everolimus

EXPERIMENTAL

Fruquintinib 4mg Qd 21 days on 7 days off; Everolimus 5mg Qd; 28 day cycle until disease progression or intolerable adverse events

Drug: Fruquintinib and Everolimus

Fruquintinib(5mg) plus Everolimus

EXPERIMENTAL

Fruquintinib 5mg Qd 21 days on 7 days off; Everolimus 5mg Qd; 28 day cycle until disease progression or intolerable adverse events

Drug: Fruquintinib and Everolimus

Interventions

Fruquintinib and Everolimus DRUG

Fruquintinib and Everolimus

Fruquintinib(3mg) plus Everolimus; Fruquintinib(4mg) plus Everolimus; Fruquintinib(5mg) plus Everolimus

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 and ≤75 years of age
• Able to Sign informed consent form independently.
• Stage IV clear cell renal cell carcinoma.
• Subjects must have progressed after IO-TKI therapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
• Subjects must have normal organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dL;Absolute neutrophil count (ANC) ≥ 1,500/mcL; Platelets ≥ 100,000/mcL, independent of transfusions/growth factors within 3 months of treatment start;
• Serum potassium ≥ 3.5 mmol/L;
• Serum total bilirubin ≤ 2.0 x upper limit of normal (ULN) (except in subjects with Gilbert's syndrome who have a total bilirubin \> 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1.5 x ULN, subject may be eligible);Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN;Serum albumin ≥ 3.0 g/dL;Serum creatinine \< 2.0 x ULN.

You may not qualify if:

• Have received approved systemic anti-tumor therapy within 2 weeks prior to the first administration, including but not limited to:TKI (TKI with a washout period of 2 weeks or 5 half-lives, whichever is shorter), traditional Chinese medicine treatment (Chinese medicine treatment with anti-tumor indications in the instructions, which can be washed out for 1 week before the first administration), cytokine therapy, etc; Has received any one of the drugs in this study for treatment
• Participated in or participated in another intervention clinical study within 4 weeks prior to the first administration, except for an observational (non intervention) clinical study or being in the survival follow-up stage of an intervention study;
• Within 60 days prior to the first medication use, significant surgical procedures (such as craniotomy, thoracotomy, or laparotomy, as defined by the researcher) have been performed;
• Have undergone any surgery or invasive treatment within 4 weeks prior to the first medication use (fistula surgery requires stable fistula formation for 4 weeks, except for renal/bladder puncture fistula, puncture biopsy, and venous catheterization); Or unhealed wounds, ulcers, fractures, or significant surgery expected during the course of this study (note: local treatment for isolated lesions is acceptable for palliative purposes);
• Received radiation therapy within one week before the first medication; Received curative radiotherapy (including over 25% bone marrow radiotherapy) within the first 4 weeks of screening;
• Perform close range radiotherapy (such as implanting radiation particles) within 60 days before the first medication;
• Allergies to fruquintinib, everolimus or other rapamycin analogues (sirolimus etc), or their excipients;
• Individuals who have developed other malignant tumors within the 5 years prior to enrollment, excluding clinically cured cervical carcinoma in situ/basal cell carcinoma of the skin/squamous cell carcinoma of the skin/ductal carcinoma in situ of the breast, and localized prostate cancer that has undergone radical treatment;
• Known to have central nervous system (CNS) metastasis and/or spinal cord compression and/or cancerous meningitis, with a history of leptomeningeal carcinoma;
• The known history of liver diseases with clinical significance, including those with active viral hepatitis (when hepatitis B virus surface antigen (HBsAg) and or hepatitis B virus core antibody (HbcAb) are positive, hepatitis B B virus (HBV) DNA\>10000 copies/mL or\>2000 IU/mL; Hepatitis C virus (HCV) antibody positive and HCV RNA positive, or other active hepatitis with clinically significant moderate to severe cirrhosis;
• The patient currently has digestive tract diseases such as active gastric and duodenal ulcers, ulcerative colitis, or active bleeding from unresectable tumors, or other conditions determined by the researcher that may cause gastrointestinal bleeding or perforation; Or those who have a history of gastrointestinal perforation or fistula and have not recovered after surgical treatment;
• Cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting surgery within the first 6 months of screening; Congestive heart failure: New York Heart Association (NYHA) grade ≥ 2; Left ventricular ejection fraction (LVEF)\<50%;
• The patient currently has uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg) even after receiving standardized treatment;
• The patient currently has any disease or condition that affects drug absorption, or the patient is unable to administer the medication orally;
• Patients with evidence of bleeding tendency or medical history within 2 months prior to the first medication (such as black stools, vomiting blood, hemoptysis, bloody stools, etc.), regardless of severity (excluding hemorrhoid bleeding);

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (1)

Peking University First Hospital

Beijing, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

HMPL-013; Everolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Central Study Contacts

Zhisong He, M.D

CONTACT

+8610-83572418; wyj7074@sohu.com

Kaiwei Yang, M.D

CONTACT

13811501435; 13811501435@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2023
• First Posted: March 19, 2024
• Study Start: February 21, 2024
• Primary Completion: August 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 19, 2024

Record last verified: 2024-03

Locations

CN (1)