Phase I Trial to Investigate Cafusertib Hydrochloride Monotherapy in Chinese Patients With Advanced Solid Tumours

Study Overview
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Brief Summary
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A Phase I, Open-label, Dose-escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity of Cafusertib Hydrochloride in Patients With Advanced Solid Tumors

Detailed Description
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To investigate safety, tolerability of cafusertib in Chinese patients with Advanced Solid Tumors that are not eligible for conventional or intensive treatment. The dose of cafusertib will be escalated to determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of cafusertib in advanced cancer patients. At the same time, pharmacokinetic characteristics and preliminary efficacy of cafusertib will be observed in advanced cancer patients. To determine the recommended dosage regimen for phase II.

Official Title
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A Phase I, Open-label, Dose-escalation Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity of Cafusertib Hydrochloride in Patients With Advanced Solid Tumors

Conditions
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Neoplasms

Intervention / Treatment
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* Drug: Cafusertib Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients age 18 years to 75 years at the time of informed consent Eastern Cooperative Oncology Group performance status score of 0-2 at screening Life expectancy of at least 12 weeks At least one target tumor lesion has not been irradiated and can accurately be measure. Patients with histologically or cytologically confirmed diagnosis of advanced solid tumors, who had failed conventional treatment, or for whom no therapy of efficacy existed. Signed informed consent consistent with Chinese Good Clinical Practice. Male or female patients of child-producing potential must agree to use appropriate contraceptive measures (hormones or barrier or abstinence) during the study and for 90 days after the last day of treatment, serum pregnancy test must be negative within 7 days prior to initiation of study treatment, infertile women is defined as hysterectomy, ovariotomy or menopause for at least 12 months. Adequate bone marrow, renal and hepatic function parameters: ANC more than 2000/mm3, platelet count more than 100 000/mm3, hemoglobin more than 90 g/L; Total bilirubin less than 1.5 x upper limit of normal，ALT and AST less than 2.5 x upper limit of normal，less than 5.0 x upper limit of normal in case of liver metastases; serum creatinine less than 1.5 x upper limit of normal, creatinine clearance rate more than 50 ml/min (as calculated according to Cockcroft-Gault formula for GFR estimate); Relatively normal ECG (electrocardiogram), QT intervals below 450 ms (male) ,QT intervals below 470 ms (female); LVEF more than 50%. Exclusion Criteria: Uncontrolled accumulation of coelomic fluid. Any anti-cancer therapy, including chemotherapy, hormonal therapy, biologic therapy or radiotherapy within 4 weeks prior to initiation of study treatment, or received nitrourea or mitomycin chemotherapy within 6 weeks prior to initiation of study treatment. Side effects/toxicities of such surgery that have not recovered to CTCAE grade 1 Patients who can't be interrupted use drugs, which may cause QT prolongation (see annex 2) Patients with meningioma or current symptomatic brain metastases Co-existing malignancy or malignancies diagnosed within the last 5 years with the exception of completely removed skin basal cell carcinoma or cervical cancer in situ Concurrent anti-tumor therapy Involved in other clinical trials less than 4 weeks prior to Day 1 Known hypersensitivity to more than two substances or the trial drugs and their excipients Patients with serious infections Patients with history of immune deficiency, including positivity to HIV antibody, or other acquired, congenital immunodeficiency disease, or history of organ transplantation Known positivity to hepatitis B antigen or hepatitis C antibody Patient with other serious diseases, in the investigator's opinion, can bring patients great risk. Including but not limited to the following: unstable cardiac diseases (history of myocardial infarction within 6 months prior to Day 1, New York Heart Association Class III or greater, with poorly controlled atrial fibrillation or hypertension), need long-term steroids or immunosuppressive therapy of diseases, such as rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus Pregnant(positive pregnancy test) or lactating women Active alcohol abuse or heavy smoker A previous history of neurological or psychiatric disorders, including epilepsy or dementia Subject is thought unfit for this study by investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cafusertib Hydrochloride<br>Cafusertib Hydrochloride d1q3w | Drug: Cafusertib Hydrochloride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MTD of cafusertib based on the incidence of dose limiting toxicities |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 |  | 6 weeks | 
| Incidence and intensity of Adverse Events according to Common Toxicity Criteria for AEs (CTCAE version 4.0) |  | 6 weeks | 
| Occurrence of dose limiting toxicities (DLT) |  | 4 weeks | 
| Max concentration (Cmax) of cafusertib |  | 3 weeks | 
| AUC of cafusertib |  | 3 weeks | 
| Elimination half-life(T1/2) of cafusertib |  | 3 weeks |