JS015 in combination with chemotherapy and bevacizumab as second-line treatment in advanced colorectal cancer
Phase 2
- Conditions
- colorectal cancer
- Registration Number
- ChiCTR2400088962
- Lead Sponsor
- Shanghai East Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria
- Aged 18-75 years (males and females)<br>2. Histologically confirmed adenocarcinoma of the colon or rectum. Subjects must have experienced disease progression following first-line treatment with a fluoropyrimidine-based combination regimen (including progression during maintenance therapy). Subjects who have received FOLFOXIRI as first-line treatment are not eligible for screening. If disease progression occurred during neoadjuvant/adjuvant treatment or within 6 months after the last dose, it is considered as first-line treatment failure, making the subject unsuitable for inclusion.<br>3. ECOG score of 0-1;<br>4. Expected survival =12 weeks.<br>5. At least one measurable lesion according to RECIST 1.1 criteria.<br>6. Normal major organ function meeting the following requirements:<br> a. Absolute neutrophil count (ANC) = 1.5 × 10^9/L.<br> b. Platelet count = 100 × 10^9/L.<br> c. Hemoglobin = 90.0 g/L.<br> d. Serum creatinine = 1.5 times the upper limit of normal (ULN).<br> e. Creatinine clearance = 50 mL/min, as calculated using the Cockcroft-Gault formula.<br> f. Total bilirubin = 1.5 × ULN or = 3 × ULN for subjects with Gilbert’s syndrome.<br> g. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) =2.5×ULN (no liver metastasis) or =5×ULN (if liver metastasis exists)<br> h. Urine protein qualitative =1+; if urine protein qualitative =2+, 24-hour urine protein quantitative test is required, if 24-hour urine protein quantitative <1 g, it is acceptable;<br> i. International normalized ratio (INR) or activated partial thromboplastin time (APTT) =1.5×ULN<br> j. Electrocardiogram Friderica-corrected QT interval (QTcF): =470 (female) or =450 (male) msec, and no history of congenital long QT syndrome<br> k. Echocardiogram: left ventricular ejection fraction (LVEF) =50%<br>7. Subjects with reproductive potential, both females and males, must agree to use effective contraception during the study and for 6 months after the last dose. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first dose and must not be breastfeeding.<br>8. Ability to provide signed informed consent, including compliance with the requirements and restrictions listed in the informed consent form (ICF) and the study protocol.
Exclusion Criteria
- Leptomeningeal metastasis or active brain metastasis.<br>2. Presence of pleural effusion, peritoneal effusion, or pericardial effusion that requires repeated treatment (e.g., puncture or drainage). <br>3. A history of immunodeficiency, including positive human immunodeficiency virus (HIV) test, or known history of allogeneic organ transplant or allogeneic hematopoietic stem cell transplant. <br>4. Severe cardiovascular or cerebrovascular diseases. <br>5. Occurrence of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months before the first study treatment.<br>6. Severe infection (CTCAE 5.0 grade >2) requiring hospitalization, such as severe pneumonia, bacteremia, or infection with complications, occurring within 28 days prior to the first study treatment. <br>7. Active tuberculosis, hepatitis B, or hepatitis C. <br>8. The patient has had other malignancies, except for subjects who have undergone curative treatment and have no known active disease for more than 5 years and are at low risk for recurrence (e.g., adequately treated basal cell carcinoma or squamous cell carcinoma of the skin). <br>9. Subjects are not eligible for screening if:<br> a. Imaging during the screening period shows that the tumor surrounds important blood vessels or exhibits significant necrosis or cavitation, which, in the investigator's opinion, may rise the bleeding tendency;<br> b. Clinical symptoms of bowel obstruction and/or GI obstruction, including partial obstruction related to the underlying disease, occurred within 6 months before the first study treatment;<br> c. Severe, unhealed, or dehiscent wounds, active ulcers, or untreated fractures;<br> d. Clinically significant hemoptysis (=1/2 teaspoon) or tumor bleeding of any cause within one month before the first study treatment;<br> e. Uncontrolled hypertension (systolic blood pressure =150 mmHg and/or diastolic blood pressure >100 mmHg) or a history of hypertensive crisis or hypertensive encephalopathy;<br> f. Other conditions that the investigator deems unsuitable for bevacizumab treatment.<br>10. Unresolved toxicity from prior anti-tumor treatment that has not returned to = grade 1 according to CTCAE 5.0 or to the level specified in the inclusion/exclusion criteria, except for toxicities that are well controlled, do not affect the subject's safety, and do not impair compliance with the study medication as judged by the investigator.<br>11. Subjects who experienced drug-related adverse events leading to permanent discontinuation of bevacizumab or similar treatments.<br><br>12. Subjects who received the following treatments or medications before the first dose:<br> a. Chemotherapy, immunotherapy, radiotherapy, or other anti-tumor treatments within 21 days before the first dose; oral fluoropyrimidines, small-molecule targeted drugs, anti-tumor Chinese herbal medicine, or palliative radiotherapy (e.g., for bone lesions or cranial lesions) within 14 days before the first dose;<br> b. Major surgery within 28 days before the first dose; core needle biopsy or other minor surgery (excluding placement of a vascular access device) within 7 days before the first dose;<br> c. Systemic treatment with corticosteroids (daily dose >10 mg prednisone or equivalent) or other immunosuppressants within 2 weeks before the first dose; inhaled or topical steroids and prophylactic medications (e.g., for infusion reactions/allergic reactions) are allowed;<br> d. Vaccination with live or attenuated live
Study & Design
- Study Type
- Interventional study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Objective response rate;
- Secondary Outcome Measures
Name Time Method Progression-free survival;Overall survival;Safety;Duration of Response;Disease control rate;