Trial Title:
Fruquintinib Plus Camrelizumab and Capecitabine as Salvage Therapy After Progression on FOLFOXIRI-based First-line Treatment in Patients With Unresectable/Metastatic Colorectal Cancer
NCT ID:
NCT06148402
Condition:
Unresectable/Metastatic Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Capecitabine
Conditions: Keywords:
Fruquintinib
Camrelizumab
Capecitabine
mCRC
salvage therapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
fruquintinib 5 mg once daily, 2 weeks on/1 week off, plus camrelizumab 200 mg Q3W and
capecitabine 750mg/square meter twice, 2 weeks on/1 week off, q3w
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Fruquintinib plus camrelizumab and capecitabine
Description:
fruquintinib 5 mg once daily, 2 weeks on/1 week off, plus camrelizumab 200 mg Q3W and
capecitabine 750mg/square meter twice, 2 weeks on/1 week off, q3w
Arm group label:
Fruquintinib plus camrelizumab and capecitabine
Summary:
FOLFOXIRI-based regimen is more used as a first-line therapeutic approach for patients
diagnosed with unresectable or metastatic colorectal cancer for its superior efficacy.
However, there are no standard recommendations for second-line therapy after progression
on FOLFOXIRI with or without targeted therapy. Here, the investigators conduct this
open-label, single arm phase II study to evaluate whether fruquintinib in combination
with camrelizumab and capecitabine can be the salvage therapy following FOLFOXIRI based
regimen for mCRC. Patients diagnosed with unresectable or metastatic colorectal cancer
progression on FOLFOXIRI-based regimen are included;or patients have progression or
untolerated toxicity with irinotecan, oxaliplatin and fluorouracil successively within
one year; patients with BRAF mutation were allowed to receive BRAF inhibitor therapy with
or without MEK inhibitor therapy after FOLFOXIRI-based regimen.
Patients participated in this study will receive fruquintinib 5 mg once daily, 2 weeks
on/1 week off, plus camrelizumab 200 mg Q3W and capecitabine 750mg/square meter twice, 2
weeks on/1 week off, repeated every three weeks. The primary endpoint is Objective
Response Rate(ORR). The investigators estimated that 30 patients were necessary.
Secondary endpoints include progression-free survival, overall survival, safety, and
exploratory ctDNA for efficacy prediction for unresectable or metastatic colorectal
cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Metastatic or locally advanced, unresectable colorectal cancer confirmed by
histology or cytology
2. The occurrence of metastases after radical resection of colorectal cancer does not
require additional histological or cytological confirmation unless more than 5 years
since surgery for the primary tumor
3. Progression or toxicity intolerance of first-line treatment with or without targeted
drugs (bevacizumab or cetuximab) with FOLFOXIRI regimen or the sequential
administration of irinotecan, oxaliplatin, and fluorouracil within a year; if
patients with BRAF mutations, who have been treated with BRAF inhibitor alone or in
combination with MEK inhibitor also can be included.
4. Target lesion defined by the Response Evaluation Criteria in Solid Tumor (RECIST
criteria)
5. Age ≥18 years old, performance status (ECOG) score ≤ 2
6. Estimated expectancy life at least 12 weeks
7. Adequate blood, liver and kidney function, as follows:
1. Hemoglobin ≥8g/dl,
2. neutrophil absolute count ≥1000/μL,
3. platelets ≥ 75,000 /μL;
4. Total bilirubin ≤1.5 x upper limit of normal (ULN),
5. alkaline phosphatase, aspartate aminotransferase (AST (SGOT) and alanine
aminotransferase (ALT (SGPT)) ≤2.5 x ULN (if liver metastasis is present, ≤5 x
ULN),
6. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance >50mL/min
(calculated according to Cockcroft Gault formula),
7. urinary protein excretion (if protein >30 mg/dL or 2+, 24-hour urinary protein
quantity must ≤1g)
8. International Normalized Ratio (INR) or activated partial thromboplastin time (APTT)
<1.5 x ULN (thromboembolic event must be ruled out if D-dimer is abnormal)
9. Negative pregnancy test within 7 days before enrollment; Pregnancy tests can only be
omitted in women who do not have any reproductive potential (e.g., postmenopausal
women who had amenorrhea ≥2 years or prior hysterectomy or bilateral oophorectomy).
Fertile wo-men and men must consent to the use of appropriate contraception at the
time of enrollment and during study participation. If a woman becomes pregnant or
suspects that she is pregnant while participating in this study, she must notify her
physician immediately; Breastfeeding women must be excluded
10. Consent to provide blood samples for specific relevant analyses
11. Have the ability to understand and sign the written informed consent
Exclusion Criteria:
1. Received antitumor chemotherapy or biotherapy within 28 days prior to the first use
of the investigational drug. The exception is a single dose of radiotherapy up to
8Gy for pain relief of non-target lesion during the first 14 days of enrollment
2. Untreated or symptomatic brain metastases
3. The exclusion criteria of fruquintinib are as follows:
1. History of heart disease: Congestive heart failure (CHF) grade II or higher,
according to the New York Heart Association (NYHA); Active coronary artery
disease and myocardial infarction within 6 months prior to study initiation;
New angina or unstable angina (occurrence at rest) that have not been evaluated
within 3 months; arrhythmias that require antiarrhythmic therapy; except in
participants who have been treated and who the investigator believes have
stable/controlled disease;
2. Uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood
pressure >90 mmHg) and a history of hypertensive crisis or hypertensive
encephalopathy;
3. History of arterial thrombosis or embolism events (within 6 months)
4. Critical vascular diseases (such as aortic aneurysm, aortic dissection,
symptomatic peripheral vascular disease)
5. People with bleeding tendency or coagulation disorder
6. Had major surgery (including open biopsy, severe trauma, etc.) within 14 days
prior to study enrollment, or expected to require major surgery during the
study period, and had minor surgery (excluding Implantable Venous Access Port
or peripherally inserted central venous catheter) within 7 days prior to study
enrollment
7. Abdominal fistula, gastrointestinal perforation, peptic ulcer or abdominal
abscess in the past 6 months
8. Severe, non-healing wounds, ulcers or fractures
9. History of posterior reversible encephalopathy syndrome
10. previous treatment with fruquintinib;
4. Inability to swallow tablets, malabsorption syndrome or any condition affecting
gastrointestinal absorption; Patients with incomplete obstruction/obstruction
syndrome/intestinal obstruction signs/symptoms at initial diagnosis may be admitted
to the study if they have received definitive treatment (such as surgical) to
resolve symptoms;
5. Active autoimmune disease or history of autoimmune disease with possible recurrence
(including but not limited to: autoimmune hepatitis, interstitial pneumonia,
uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism,
hypothyroidism [controllable only by hormone replacement therapy can be included]);
Participants with non-systemic skin diseases such as vitiligo, psoriasis, and
alopecia, type 1 diabetes controlled with insulin, or asthma in complete remission
in childhood without any intervention as adults can be enrolled; Patients with
asthma requiring medical intervention with bronchodilators are excluded;
6. Immunosuppressive or systemic hormone therapy for immunosuppressive purposes (dose
>10mg/ day prednisone or other therapeutic hormone) within 14 days prior to
initiation of study therapy
7. Severe infection within 4 weeks prior to initiation of study treatment, including
but not limited to hospitalization for complications of infection, bacteremia, or
severe pneumonia; Oral or intravenous administration of therapeutic antibiotics
within 2 weeks prior to initiation of study treatment (patients receiving
prophylactic antibiotics, for example, to prevent urinary tract infections or
exacerbation of chronic obstructive pulmonary disease are eligible for study
participation)
8. Patients with congenital or acquired immune deficiency (such as HIV infection)
9. Have received live attenuated vaccines within 28 days prior to initiation of study
treatment, or are expected to require such vaccines during camrelizumab treatment or
within 60 days after the last administration of camrelizumab
10. According to the investigator's judgment, the patient has other factors that may
affect the study results or lead to the forced termination of the study, such as
alcoholism, drug abuse, other serious diseases，including mental illness，requiring
combined treatment, serious laboratory abnormalities, and family or social factors
which will affect the safety of the patient
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Address:
City:
Guangzhou
Zip:
510000
Country:
China
Status:
Recruiting
Contact:
Last name:
Qiong Yang, Doctor
Phone:
13632341201
Email:
yangqiong05@126.com
Contact backup:
Last name:
kaicong zhang, master
Phone:
+8618033317733
Email:
lifesummerflower@163.com
Investigator:
Last name:
Qiong Yang, Doctor
Email:
Principal Investigator
Start date:
November 8, 2023
Completion date:
June 30, 2026
Lead sponsor:
Agency:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Agency class:
Other
Source:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06148402
