Trial Title:
A Study of SC-0191 in Subjects With Metastatic Colorectal Cancer
NCT ID:
NCT06363552
Condition:
Metastatic Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Bevacizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Single (Participant)
Intervention:
Intervention type:
Drug
Intervention name:
SC0191
Description:
The SC0191 tablet is taken orally at a dose of 300mg once daily. Each treatment cycle
consists of 28 days. Medication is administered on days 1 to 3, days 8 to 10, days 15 to
17, and days 22 to 24 of each cycle.
Arm group label:
SC0191
Intervention type:
Drug
Intervention name:
SC0191 + Bevacizumab
Description:
1. The SC0191 tablet is taken orally at a dose of 300mg once daily. Each treatment
cycle consists of 28 days. Medication is administered on days 1 to 3, days 8 to 10,
days 15 to 17, and days 22 to 24 of each cycle.
2. Bevacizumab injection is administered intravenously at a dose of 5mg/kg on day 1 and
day 15 of each treatment cycle.
Arm group label:
SC0191 + Bevacizumab
Intervention type:
Drug
Intervention name:
SC0191 + 5-FU/LV
Description:
1. The SC0191 tablet is taken orally at a dose of 300mg once daily. Each treatment
cycle consists of 28 days. Medication is administered on days 1 to 3, days 8 to 10,
days 15 to 17, and days 22 to 24 of each cycle.
2. Calcium folinate 400mg/m2 intravenous infusion (over 2 hours or more), on the first
day, followed by 5-fluorouracil 400mg/m2 intravenous bolus injection, then
continuous intravenous infusion of 1200mg/m2/day for 2 days.
Arm group label:
SC0191 + 5-FU/LV
Summary:
The goal of this clinical trial is to evaluate the preliminary safety and efficacy of
SC0191 as single agent or in combination with bevacizumab or 5-FU/LV in advanced
colorectal cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Subjects voluntarily participate in the clinical study and sign an informed consent
form;
2. Male or female subjects aged ≥18 years;
3. Subjects diagnosed with stage IV colorectal cancer confirmed by histology or
cytology and not suitable for curative surgical treatment;
4. Subjects who have previously received fluoropyrimidine-based chemotherapy,
oxaliplatin, and irinotecan with or without anti-EGFR or anti-VEGF targeted therapy,
and experienced disease progression or intolerance to the most recent treatment
regimen; the number of prior lines of systemic antitumor therapy for advanced
colorectal cancer does not exceed 2 lines;
5. ECOG performance status of 0 to 1;
6. Expected survival of ≥3 months;
7. At least one measurable lesion according to RECIST 1.1 criteria, defined as a lesion
with a longest diameter ≥10 mm on CT scan or MRI (excluding lymph nodes) or a short
diameter ≥15 mm for lymph nodes. Lesions located in previously irradiated or
otherwise locally treated areas are generally not considered measurable unless there
is documented disease progression;
8. Adequate organ function and bone marrow hematopoietic function;
9. Fertile subjects (both male and female) must agree to use a reliable method of
contraception (hormonal or barrier method, or abstinence) with their partners for at
least 6 months from the time of signing the informed consent form until the last
dose of the study drug; female subjects of childbearing potential must have a
negative pregnancy test within 14 days before the first use of the investigational
drug.
Exclusion Criteria:
1. Subjects known to be MSI-H who have not received immunotherapy;
2. Subjects with spinal cord compression, symptomatic/unstable brain metastases, or
leptomeningeal metastases. Exclusion: Subjects with stable symptoms of brain
metastases after prior treatment (completion of definitive radiotherapy and/or
surgery, cessation of corticosteroid therapy, and stable symptoms for at least 14
days);
3. Subjects with radiological evidence of tumor invasion or encasement of major vessels
(Cohort A);
4. Subjects with uncontrollable pleural effusion, ascites, or pericardial effusion at
screening;
5. Subjects with a history of other malignant tumors within 5 years prior to study drug
initiation, except for early-stage tumors cured by curative treatment, such as basal
cell carcinoma or squamous cell carcinoma of the skin, cervical carcinoma in situ,
ductal carcinoma in situ of the breast, superficial bladder cancer, localized
prostate cancer, etc.;
6. Subjects with significant cardiovascular diseases, including NYHA class II-IV heart
failure, congestive heart failure, second-degree or higher atrioventricular block,
myocardial infarction within the past 6 months, unstable arrhythmias or angina,
significant QT interval prolongation (baseline-corrected QTc interval >470
milliseconds on ECG), stroke within the past 6 months, or PTCA (percutaneous
transluminal coronary angioplasty) or CABG (coronary artery bypass grafting) within
the past 6 months;
7. Subjects with poorly controlled hypertension;
8. Subjects with viral infectious diseases at screening meeting the following criteria:
9. HIV seropositivity;
10. Hepatitis B: HBsAg positivity with HBV-DNA quantification above the upper limit of
normal;
11. Hepatitis C: HCV antibody positivity with HCV-RNA quantification above the upper
limit of normal;
12. Subjects with active infections requiring systemic antimicrobial therapy as judged
by the investigator, deemed unsuitable for participation in this study;
13. Subjects who have undergone allogeneic tissue/organ transplantation;
14. Subjects with malabsorption syndrome or other gastrointestinal abnormalities that
may significantly affect oral drug absorption (such as ulcerative lesions,
uncontrollable nausea, vomiting, diarrhea, malabsorption syndrome, and small bowel
resection, etc.);
15. Subjects with hereditary bleeding or coagulation disorders, or a history of severe
non-traumatic bleeding, or a history of ineffective platelet transfusion (within the
past 1 year before initial study drug administration), or any disease that
significantly increases the risk of bleeding;
16. Subjects with a history of any of the following during treatment with
Bevacizumab-based regimens (or biosimilars): venous or arterial thromboembolic
events, gastrointestinal perforation, grade 4 hypertension, grade 3 proteinuria, or
grade 3 or higher bleeding events (Cohort A).
17. Subjects who have undergone major surgery, open biopsy, or experienced severe
traumatic injury within 28 days before first use of the investigational drug, or are
expected to undergo major surgery during the study. Subjects who have undergone
minor surgery within 7 days before first use of the investigational drug, such as
fine needle aspiration or core biopsy. Subjects with a history of esophageal varices
or bleeding peptic ulcer within 3 months before first use of the investigational
drug (Cohort A).
18. Known history of dihydropyrimidine dehydrogenase (DPD) deficiency. History of
discontinuing fluoropyrimidine treatment due to ≥3 grade diarrhea (Cohort B).
19. Subjects with a history of interstitial lung disease, drug-induced interstitial lung
disease, radiation pneumonitis requiring corticosteroid treatment, or any clinical
evidence suggesting active interstitial lung disease;
20. Subjects diagnosed with autoimmune diseases during screening or receiving long-term
systemic corticosteroid therapy (dose exceeding 10 mg/day of prednisone or
equivalent) or any other form of immunosuppressive therapy due to autoimmune
diseases;
21. Subjects whose toxicity from prior anticancer therapy has not resolved to ≤ grade 1
(CTCAE 5.0) (excluding alopecia, decreased hearing, and stable endocrine disorders
treated with alternative therapies);
22. Subjects previously treated with WEE1 inhibitors;
23. Subjects with a history of hypersensitivity reactions to SC0191, Bevacizumab (Cohort
A), fluoropyrimidines (Cohort B), calcium folinate (Cohort B) active ingredients, or
their inactive excipients or similar drugs;
24. Subjects who received radiation therapy to more than 25% of the bone marrow area
within 28 days before first use of the investigational drug;
25. Subjects vaccinated with live vaccines within 28 days before first use of the
investigational drug.
26. Subjects who received chemotherapy, biologic therapy, endocrine therapy, or other
antitumor therapy within 28 days before first use of the investigational drug; or
received small molecule targeted therapy within 28 days or 5 half-lives (whichever
is shorter) before first use of the investigational drug; or received traditional
Chinese medicine for antitumor therapy within 7 days before first use of the
investigational drug;
27. Subjects who received systemic corticosteroids (prednisone equivalent >10 mg/day) or
other immunosuppressive therapy within 14 days before first use of the
investigational drug, except for local, ocular, intra-articular, intranasal, and
inhalational corticosteroid therapy; or received corticosteroids for prophylactic
treatment (e.g., prevention of contrast agent allergy) ;
28. Subjects who received moderate or potent inhibitors of CYP3A4 (such as amprenavir,
atazanavir, boceprevir, clarithromycin, conivaptan, darunavir, diltiazem,
erythromycin, foscarnet, indinavir, itraconazole, ketoconazole, lopinavir,
mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir,
telithromycin, verapamil, voriconazole, etc.) or moderate or potent inducers of
CYP3A4 (such as carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin,
primidone, rifampin, efavirenz, modafinil, etc.) within 14 days before first use of
the investigational drug;
29. Subjects who require regular use of proton pump inhibitors (PPIs) during the study
or received PPI therapy within 14 days before first use of the investigational drug
(such as omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole,
etc.);
30. Subjects who require long-term therapeutic doses of anticoagulants or antiplatelet
drugs (prophylactic use of low-dose anticoagulants is allowed, provided that the
anticoagulation parameters specified in the inclusion criteria are met); low-dose
anticoagulants may be used to maintain venous catheter patency;
31. Subjects with psychiatric disorders or poor compliance;
32. Pregnant or lactating female subjects;
33. Subjects whom the investigator considers to have other serious systemic medical
history, or for other reasons are not suitable for participation in this clinical
study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Zhongshan Hospital Affiliated to Fudan University
Address:
City:
Shanghai
Zip:
200032
Country:
China
Start date:
May 2024
Completion date:
December 2025
Lead sponsor:
Agency:
Tianshu Liu
Agency class:
Other
Source:
Shanghai Zhongshan Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06363552
