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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06283134
Other study ID # BJCT-CMU1H-02
Secondary ID
Status Not yet recruiting
Phase Phase 1
First received
Last updated
Start date April 2, 2024
Est. completion date December 1, 2027

Study information

Verified date February 2024
Source China Medical University, China
Contact Shuhui Song, bachelor
Phone 15004240769
Email 593900927@qq.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a phase I, open-label clinical study of BioTTT001 in combination with Toraplizumab and Regorafenib in patients with liver metastases from colorectal cancer.


Description:

This study includes a dose escalation phase and a dose expansion phase. The dose escalation phase will adopt a 3+3 design. Subjects were first treated with BioTTT001 monotherapy (hepatic artery infusion, administered every 2 weeks, D1 and D15 for a total of two doses) after enrollment. If the subject does not develop dose-limiting toxicity (DLT) in the monotherapy stage and is judged to be safe and tolerable by the investigator, the subject will enter the treatment phase of BioTTT001 in combination with toripalimab and regorafenib( toripalimab 80mg iv. D1 and D15 , BioTTT001 5×10^7 viral particle (VP)/5×10^8 VP/5×10^9 VP/1×10^10 VP hepatic arterial infusion (HAI.) D2 and D16 , regorafenib 80 mg Po. D1-D21; 4 weeks per cycle), and the dose of BioTTT001 will be determined according to the safety observation results in the monotherapy phase. In the dose expansion phase, different dose groups can be expanded, and the total number of enrolled subjects is expected to be 30 for further safety, tolerability, pharmacokinetics and preliminary efficacy evaluation.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 40
Est. completion date December 1, 2027
Est. primary completion date December 1, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years to 70 Years
Eligibility Inclusion Criteria: 1. Age range from 18 to 70 years old (including the threshold), no gender restrictions; 2. Patients with a definitive histopathological or cytological diagnosis of colorectal cancer with hepatic metastases who have received and failed at least second-line standard therapy in the past, or who have been assessed by the investigator to be unsuitable for standard therapy; 3. At least one assessable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; 4. WBC=3.0×10^9/L; ANC=1.5×10^9/L (without cytokine therapy within one week before the screening ); Hb=90g/L(without blood transfusion within one week before the screening);PLT=90×10^9/L(without Platelet transfusion or thrombopoietin (TPO) within one week before the screening);ALT and AST=5×ULN;Cr=1.5×ULN or CCr>50mL/min; TBIL=1.5×ULN; APTT=1.5×ULN and INR/PT=1.5×ULN; 5. ECOG 0~2; 6. Expected survival = 3 months; 7. Consent to contraception; 8. Understand and voluntarily sign a written ICF and be willing to comply with all trial requirements. Exclusion Criteria: 1. Known allergy to the investigational drug or its components; 2. Previous treatment with other adenovirus drugs; 3. Patients with active autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, etc.), except type 1 diabetes, hypothyroidism that only needs hormone replacement therapy, and skin diseases that do not need systemic treatment (such as vitiligo, psoriasis or alopecia); 4. Received treatment with nitrosourea or mitomycin C within 6 weeks before the first dose of BioTTT001; received oral fluorouracil and small molecule targeted drug therapy within 2 weeks or 5 half-lives of the drug within 2 weeks before the first dose of BioTTT001; received traditional Chinese medicine therapy with anti-tumor indications within 2 weeks before the first dose of BioTTT001; received chemotherapy, radiotherapy, biological therapy other than the drugs mentioned above within 28 days before the first dose of BioTTT001; 5. Patients who have not recovered from the adverse reactions of previous treatments (the treatment-related toxicity = grade 2, except for alopecia, pigmentation or other tolerable events judged by the investigator ). 6. History of other malignancies (except cured basal cell skin cancer, cervical carcinoma in situ, Papillary carcinoma of thyroid gland, low-risk GIST etc.) within 5 years before study drug administration; 7. Patients who have undergone any major surgery (except needle biopsy, etc.) or severe trauma within 4 weeks before the first dose of BioTTT001; 8. Patients who have been treated with high-dose systemic corticosteroids (prednisone > 10 mg/day or equivalent doses) or other immunosuppressants within 2 weeks before the first dose of BioTTT001; 9. NYHA=grade 3; LVEF<50%; male QTc>450 mms, female QTc>470 mms; 10. Patients with active tuberculosis or drug-induced interstitial lung disease; 11. Patients with active infection requiring systemic anti-infective therapy; 12. In a state of immunosuppression, such as severe combined immunodeficiency disease or concurrent opportunistic infections; 13. HBsAg positive, and blood HBV DNA=100 IU/mL; anti-HCV positive; HIV positive; active syphilis; 14. Patients with pleural effusion and ascites with clinical symptoms that require repeated drainage; 15. Patients with central nervous system metastases or meningeal metastases with clinical symptoms; 16. Patients with contraindications to hepatic arterial perfusion therapy; 17. Pregnant or lactating women; 18. Patients with prior organ transplants; 19. Other reasons judged by the investigator.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
BioTTT001 hepatic artery infusion
BioTTT001 monotherapy period: BioTTT001 5×10^7 VP/5×10^8 VP/5×10^9 VP/1×10^10 VP hepatic artery infusion, administered every 2 weeks, for a total of two doses after enrollment. BioTTT001 in combination with toripalimab and regorafenib period: BioTTT001 5×10^7 VP/5×10^8 VP/5×10^9 VP/1×10^10 VP hepatic artery infusion, D2 and D16, 4 weeks per cycle, and the dose of BioTTT001 will be determined according to the safety observation results in the monotherapy phase.
Drug:
toripalimab
BioTTT001 in combination with toripalimab and regorafenib period: toripalimab 80mg intravenous D1 and D15, 4 weeks per cycle.
regorafenib
BioTTT001 in combination with toripalimab and regorafenib period: regorafenib 80 mg oral administration, D1-D21, 4 weeks per cycle.

Locations

Country Name City State
n/a

Sponsors (2)

Lead Sponsor Collaborator
China Medical University, China Beijing Bio-Targeting Therapeutics Technology Co., Ltd

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of adverse events The incidence and severity of all types of adverse events evaluated based on NCI-CTCAE V5.0 assessment. From the enrollment to 28 days after the end-of-trial visit (i.e. end of treatment or early termination visit)
Primary MTD Maximum tolerated dose (MTD) 28 days within BioTTT001 injection in the monotherapy phase and combination therapy phase
Secondary Overall survival(OS) The time from the start of treatment to death for any cause Every 3 months until consent withdraw, death, withdrawal study, or loss of follow-up, up to 100 weeks
Secondary Progression-free survival (PFS) The time from the start of treatment to progress disease or death for any cause Every 4 weeks in the first 4 cycles ,then every 8 weeks until disease progression, consent withdraw, death or end of study during the combination therapy phase, up to 100 weeks.
Secondary Objective response rate (ORR) Objective response rate (ORR) as assessed by the investigators Imaging was performed after completion of the monotherapy phase, and tumour assessment was performed every 4 weeks in the first 4 cycles ,then every 8 weeks during the combination therapy phase
Secondary Plasma adenovirus (ADV) copies Pharmacokinetic Study (PK): Copies of ADV in plasma at various sampling points. 28 days within the first BioTTT001 injection dose
Secondary ADV copies in various sites Viral Shedding Analysis: Copies of ADV in swabs of injection sites, rectal swabs, throat swabs, and urine samples at various sampling points. 28 days within the first BioTTT001 injection dose
Secondary Serum IL-12 level Expression levels of IL-12 at various sampling points in serum. 28 days within the first BioTTT001 injection dose
Secondary Serum neutralizing antibody level Immunogenicity assessment through adenovirus neutralizing antibody detection. 28 days within the first BioTTT001 injection dose
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