Advanced Solid Tumors
Conditions
Keywords
Breast cancer, ovarian cancer, non-small cell lung cancer, gastric cancer, Paclitaxel Micelles
Brief summary
A Phase I Study of Dose Escalation and Dose Expansion To Evaluate the Safety、Tolerability、Pharmacokinetics and Preliminary Efficacy of Paclitaxel Micelles for Injection in Chinese Patients With Advanced Solid Tumor.
Detailed description
The study will be conducted in two parts. The first part is dose escalation and the second part is dose Expansion.During the course of dose escalation, 18-27 subjects will be enrolled to assess the safety、tolerability、pharmacokinetics、preliminary efficacy ,and determine the dose-limiting toxicity (DLT) and maximum tolerated dose(MTD) of Paclitaxel Micelles for Injection, and explore phase II clinical dosages. The second part will be adjusted according to the result of the first part. It will be divided into 4 groups, including advanced breast cancer group, ovarian cancer group, non-small cell lung cancer group and gastric cancer group, with 20 subjects in each group, to further evaluate the safety, tolerance, PK and anti-tumor activity of paclitaxel micelle.
Interventions
Paclitaxel Micelles for Injection was intravenously administrated for three hours, three weeks constituted one course of treatment.
DRUGPaclitaxel injection
Paclitaxel Injection was intravenously administrated for three hours, three weeks constituted one course of treatment.
Sponsors
Hangzhou Dihua Biotechnology Co., LTD.
First Affiliated Hospital of Zhejiang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Participants are required to meet all the criteria below in order to be included in the trial: 1. Confirmed diagnosis of advanced solid tumors by histological or cytological examination, participants have no effective standard anticancer therapy available or is failed to standard anticancer therapy. 2. Male or female patient, aged 18 \ 70 years. 3. Life expectancy ≥ 3 months. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 5. Participants with at least 1 measurable tumor lesion and/or assessable non-measurable lesion based on RECIST 1.1. 6. No radiotherapy, chemotherapy, immunotherapy or other anti-tumor therapy (such as experimental drugs, biological agents, Chinese herbal medicine, etc.), surgical treatment (except diagnostic biopsy), or complete recovery from previous surgery within 4 weeks prior to enrollment, and no surgical operation was planned during the study period. 7. No severe hematopoietic abnormalities(no blood transfusion, no blood products, no granulocyte colony-stimulating factor, platelet stimulating factor, or other hematopoietic growth factors were corrected within 14 days prior to the screening phase laboratory examination):Hb≥90g/L , ANC≥1.5×109/L , PLT≥100×109/L. 8. No serious organic disease of heart, liver or kidney:LVEF≥50% ; ALT(Alanine aminotransferase) or AST(Aspartate transaminase)≤2.5×upper limit of normal(ULN)(for patients with hepatic metastases, ALT or AST≤5 × ULN); TBIL(Total bilirubin)≤1.5×ULN; creatinine≤1.5×ULN and CL≥ 60 mL/min\[The calculation formula was as follows: CCR (140- age)× body weight (kg) /0.818× SCR (μmol/L), and female was calculated as ×0.85\]. 9. The coagulation function is normal:PT、APTT and INR≤1.5×ULN。 10. Participants (including partners) who are willing to follow reliable contraceptive measures during the study and until 3 months after the last dosing（such as intrauterine devices \[IUDs\], birth control pills or condoms）.Women of child-bearing age must be negative for serum HCG within 14 days prior to study enrolment and must be non-lactating。 11. Participants with voluntarily signature Informed Consent Form (ICF) before the test, and have a full understanding of the test content, process and possible adverse reactions. 12. Participants with good compliance, were available for follow-up, and volunteered to comply with study regulations.
Exclusion criteria
* Eligible participants must not meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of Paclitaxel Micelles for Injection in dose ascending and dose extension as measured by assessment of maximum tolerated dose (MTD) and dose limiting toxicity (DLT). | 2 years | MTD was determined as the dose where more than 2 out of 6 subjects experienced DLT |
| The recommended dose for the phase II study | 2 years | Determined as the recommended dose for a phase 2 study based on the adverse events and toxicities at each dose groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-t of Paclitaxel Micelles for Injection | Cycles 1(each cycle is 21 days), Day1 to Day4. | Defined as area under plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration |
| AUC0-inf of Paclitaxel Micelles for Injection | Cycles 1(each cycle is 21 days) ,Day1 to Day4. | Defined as area under plasma concentration-time curve from Hour 0 to infinity |
| λz of Paclitaxel Micelles for Injection | Cycles 1(each cycle is 21 days), Day1 to Day4. | Defined as elimination rate constant |
| t½ of Paclitaxel Micelles for Injection | Cycles 1(each cycle is 21 days), Day1 to Day4. | Defined as the apparent plasma terminal phase disposition half-life |
| CL of Paclitaxel Micelles for Injection | Cycles 1(each cycle is 21 days), Day1 to Day4. | Defined as apparent clearance |
| Cmax of Paclitaxel Micelles for Injection | Cycles 1(each cycle is 21 days) ,Day1 to Day4. | Defined as maximum observed plasma concentration |
| %AUCex of Paclitaxel Micelles for Injection | Cycles 1(each cycle is 21 days), Day1 to Day4. | Defined as AUC Extrapolated Percentage |
| Objective response rate (ORR) of Paclitaxel Micelles | Baseline to date of first documented progression or date of the patients drop out of the study, up to 24 months. | PR+CR,Imaging evaluations were performed with CT/MRI chest, abdominal, and pelvic scans |
| Disease Control Rate (DCR) of Paclitaxel Micelles | Baseline to date of first documented progression or date of the patients drop out of the study, up to 24 months. | PR+CR+SD,Imaging evaluations were performed with CT/MRI chest, abdominal, and pelvic scans |
| Progression-free survival (PFS) of Paclitaxel Micelles | Baseline to date of first documented progression or date of the patients drop out of the study, up to 24 months. | Imaging evaluations were performed with CT/MRI chest, abdominal, and pelvic scans |
| Duration of remission (DOR) of Paclitaxel Micelles | Baseline to date of first documented progression or date of the patients drop out of the study, up to 24 months. | Imaging evaluations were performed with CT/MRI chest, abdominal, and pelvic scans |
| Vz of Paclitaxel Micelles for Injection | Cycles 1(each cycle is 21 days), Day1 to Day4. | Defined as apparent volume of distribution |
| Tmax of Paclitaxel Micelles for Injection | Cycles 1(each cycle is 21 days) ,Day1 to Day4. | Defined as time to maximum plasma concentration |
Countries
China
Contacts
Primary Contactjian liu, master
Backup Contactxiaochen zhang, docter
Outcome results
None listed