Trial Title:
To Evaluate IAH0968 in Combination With CAPEOX in HER2-positive Metastatic Colorectal Cancer
NCT ID:
NCT05673512
Condition:
HER2 Gene Mutation
Conditions: Official terms:
Colorectal Neoplasms
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Triple (Participant, Care Provider, Investigator)
Intervention:
Intervention type:
Combination Product
Intervention name:
Injection of IAH0968 + CAPEOX
Description:
PLACEBO+CAPEOX in HER2 positive metastatic colorectal cancer patient
Arm group label:
IAH0968+ CAPEOX
Intervention type:
Combination Product
Intervention name:
PLACEBO+CAPEOX
Description:
PLACEBO+CAPEOX in HER2 positive metastatic colorectal cancer patient
Arm group label:
CAPEOX
Summary:
The Phase IIa of this clinical study, a dose-escalation study of IAH0968 in combination
with CAPEOX, is designed for safety and tolerability in subjects with HER2-positive
advanced or metastatic solid tumors. Phase IIb/III is an operational seamless adaptive
design consisting of two phases. Phase I (Phase IIb) was designed to initially evaluate
the efficacy and safety of IAH0968+CAPEOX in HER2-positive subjects with metastatic
colorectal cancer, using PFS.
Detailed description:
The Phase IIa of this clinical study, a dose-escalation study of IAH0968 in combination
with CAPEOX regimen, was designed to evaluate Safety and tolerability of IAH0968+CAPEOX
regimen in subjects with HER2-positive advanced or metastatic solid tumors.
Phase IIb/III uses an operational seamless adaptive design and consists of two phases.
Phase I (Phase IIb) aims to initially evaluate the efficacy and safety of IAH0968+CAPEOX
in HER2-positive subjects with metastatic colorectal cancer by PFS. Phase II (Phase III)
was designed to evaluate the efficacy and safety of IAH0968+CAPEOX versus placebo +CAPEOX
in HER2-positive subjects with metastatic colorectal cancer using PFS.
Criteria for eligibility:
Criteria:
Inclusion criteria:
1. Stage IIa only: advanced or metastatic solid tumor confirmed by histopathology or
cytology.
2. Only stage IIb and III: Patients with mCRC confirmed by histopathology or cytology,
who are not suitable for radical surgical excision or local therapy, and who have
not previously received systemic antitumor therapy for CRC (including systemic
chemotherapy, molecular targeted drug therapy, biotherapy and investigational
therapy, and have completed adjuvant chemotherapy for ≥6 months) can be admitted to
the group.
3. Age range from 18 to 75 years old (including the critical value), gender is not
limited.
4. Proof of HER2-positive (IHC) 3+, or IHC 2+ and FISH +, by immunohistochemical (IHC)
staining and/or fluorescence in situ hybridization (FISH), and wild type KRAS, NRAS,
and BRAF genes. HER2 positive status was interpreted according to the current
Chinese guidelines for detecting HER2 in gastric cancer.
5. According to the researchers' judgment, CAPEOX scheme is suitable.
6. At least one measurable lesion according to RECIST 1.1 criteria (tumor lesion
located in the area of prior radiotherapy or other local regional treatment site is
generally not considered as a measurable lesion unless it shows definite progression
or persists three months after radiotherapy).
7. The physical status score of the Eastern Oncology Consortium (ECOG) was 0-1.
8. Expected survival ≥3 months.
9. Adequate organ function: 1) Blood system (no blood transfusion or hematopoietic
stimulating factor treatment within 14 days) : absolute neutrophil count (ANC)
≥1.5×109/L, platelet count (PLT) ≥90×109/L, hemoglobin (HGB) ≥90 g /L; Liver
function: total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN), except
for Gilbert syndrome; Aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) ≤3.0 times ULN, liver metastasis or liver cancer patients need AST and ALT≤5.0
times ULN. 3. Renal function: serum creatinine (Cr) ≤1.5 ULN; If creatinine
Creatinine clearance (Ccr) ≥50 ml/min (calculated by Cockcroft-Gault formula) was
required at 1.5 ULN. Coagulation function: prothrombin International Normalized
ratio (INR) ≤1.5 ULN, activated partial thrombin time (APTT) ≤1.5 ULN.
10. Eligible patients (male and female) who are fertile must agree to use a reliable
contraceptive method (hormonal or barrier method or abstinence) with their partner
during the trial period and for at least 6 months after the last medication; Women
of reproductive age must have a negative blood or urine pregnancy test 7 days before
first use of the study drug.
11. Subjects must give informed consent to the study prior to the study and voluntarily
sign written informed consent.
Exclusion criteria:
1. Stage IIa only: chemotherapy, radiotherapy, biotherapy, endocrine therapy,
immunotherapy and other antitumor therapies were received within 4 weeks prior to
the first use of the study drug, except for the following: 1 nitrosourea or
mitomycin C was used within 6 weeks prior to the first use of the study drug; 2 Oral
administration of fluoripyritics and small molecule targeted drugs 2 weeks prior to
the first use of the study drug or within 5 half-lives of the drug, whichever is
longer; 3 Chinese patent drugs with anti-tumor indications were used within 2 weeks
prior to the first use of the investigational drug.
2. Have received other investigational drugs or treatments that are not on the market
within 4 weeks prior to use of the investigational drug.
3. Stage IIa only: Adverse reactions to previous antitumor therapy have not yet
returned to the NCI CTCAE 5.0 scale evaluation ≤ Level 1 or relevant provisions of
inclusion criteria (except for toxicities without safety risks as determined by the
investigators, such as alopecia, grade 2 peripheral neurotoxicity, stable
hypothyroidism after hormone replacement therapy, etc.).
4. Known hypersensitivity to any antibody-class drug (NCI CTCAE 5.0 rating ≥3) or to
investigational drug, CAPEOX protocol active ingredient or inactive excipients.
5. Confirmed mismatch repair defect (dMMR) or high microsatellite instability (MSI-H)
solid tumors (unless subject is unable to receive immune checkpoint inhibitors due
to a pre-existing medical condition, or unknown MSI/MMR status).
6. Had major organ surgery (excluding needle biopsy) or significant trauma, or required
elective surgery, within 4 weeks prior to initial use of the study drug.
7. Received systemic administration of corticosteroids (prednisone > 10 mg/day or
equivalent dose of the same drug) or other immunosuppressant therapy, except:
treatment with topical, ocular, intraarticular, intranasal, and inhaled
corticosteroids; Short-term use of glucocorticoids for prophylactic treatment (e.g.
to prevent shadow allergy).
8. Use of immunomodulatory drugs within 14 days (Appendix 5).
9. Received any live vaccine within 4 weeks prior to the first administration of the
study drug.
10. Have previously received allogeneic hematopoietic stem cell transplantation or organ
transplantation.
11. There are clinical symptoms of brain parenchymal metastasis or meningeal metastasis.
Patients with BMS who had been treated were enrolled if magnetic resonance imaging
(MRI) or computed tomography (CT) showed no signs of progression at least 8 weeks
after the end of treatment and 4 weeks before the first use of the study drug.
12. There is an active infection that currently requires intravenous anti-infective
therapy.
13. A history of immunodeficiency, including a positive test for human immunodeficiency
virus (HIV) antibodies.
14. Active hepatitis B (HBsAg positive and HBV-DNA≥1.0×103 copies /mL or ≥2000IU/mL,
active hepatitis C (HCV-RNA> 1.0×103 copies /mL or > 100 IU/mL).
15. Severe and uncontrollable lung disease (severe infectious pneumonia, interstitial
lung disease, etc.).
16. Have a history of serious cardiovascular and cerebrovascular diseases, including but
not limited to: 1. Have serious cardiac rhythm or conduction abnormalities, such as
ventricular arrhythmias requiring clinical intervention, degree II-III
atrioventricular block, etc.; 2 QT interval (QTcF) mean corrected by Fridericia
method > 470 ms;3 Acute coronary syndrome, congestive heart failure, aortic
dissection, stroke, or other grade 3 or above cardiovascular and cerebrovascular
events occurred within 6 months prior to initial administration;4 Present with heart
failure or left ventricular ejection fraction (LVEF)< of the New York Heart
Association (NYHA) cardiac function grade ≥II; 50%;5. Clinically uncontrollable
hypertension.
17. Have an active or past autoimmune disease with a risk of recurrence (e.g., systemic
lupus erythematosus, class Rheumatoid arthritis, vasculitis), clinically stable
autoimmune thyroid disease, type I diabetes, vitiligo, Children with cured atopic
dermatitis and psoriasis that does not require systemic treatment (within the last 2
years) are excluded.
18. Non-melanoma skin cancer that has been clinically cured for more than 2 years and is
currently suffering from other malignant tumors, limitations Exceptions include
prostate cancer, carcinoma in situ (such as cervical carcinoma in situ), etc.
19. There was clinically uncontrollable third space effusion, which was not suitable for
inclusion by the investigator.
20. Known alcohol or drug dependence.
21. Have mental disorders or poor compliance.
22. Pregnant or lactating women.
23. The investigator believes that the subjects have a history of other serious systemic
diseases or are not suitable to participate in this clinical study for other
reasons.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Hospital of China Medical University
Address:
City:
Shenyang
Country:
China
Status:
Recruiting
Contact:
Last name:
QU Xiujuan, PhD
Phone:
024-83282256
Email:
qu_xiujuan@hotmail.com
Start date:
May 12, 2023
Completion date:
March 1, 2026
Lead sponsor:
Agency:
SUNHO（China）BioPharmaceutical CO., Ltd.
Agency class:
Industry
Source:
SUNHO（China）BioPharmaceutical CO., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05673512
