Safety, Tolerability and Pharmacokinetics of Injectable PEG-Irinotecan (JK-1201I) in Patients with Malignant Solid Tumor

NCT ID: NCT04366648

Last Updated: 2024-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-04
• Study Completion Date: 2021-03-31

Brief Summary

The purpose of this clinical trial is to evaluate the safety and tolerability of injectable PEG-Irinotecan in patients with malignant solid tumors

Detailed Description

This study is a multicenter, open labeled, positive controlled, single, -combined, with multiple dose escalation trial.

The trial consists of 6 drug dose groups, which are 50mg/m2, 75mg/m2, 100mg/m2, 125mg/m2, 150mg/m2 and 180mg/m2 respectively. At each testing dose group, one patient will be treated with HCl-Irinotecan (CPT-11), at dose level of 175mg/m2.

The initial dose of 50mg /m2 will be administered once. Starting from the 75mg/m2 dose group, each patient will be given testing drug at least twice. During first and second drug administration, blood samples will be collected for PK characteristics analysis. Patients will be evaluated after every two rounds of drug delivery and preliminary efficacy of testing compound will be determined as PD, SD, CR etc.

Conditions

Solid Tumor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

50mg/m2

Starting dose, administered once only

Group Type: EXPERIMENTAL

JK-1201I

Intervention Type: DRUG

malignant solid tumor that has been confirmed by histopathology and/or cytology

75mg/m2

Second dose level, administered at least twice, first two cycles of drug delivery accompanied with PK analyses.

Group Type: EXPERIMENTAL

JK-1201I

Intervention Type: DRUG

malignant solid tumor that has been confirmed by histopathology and/or cytology

100mg/m2

Third dose level, administered at least twice, first two cycles of drug delivery accompanied with PK analyses.

Group Type: EXPERIMENTAL

JK-1201I

Intervention Type: DRUG

malignant solid tumor that has been confirmed by histopathology and/or cytology

125mg/m2

Forth dose level, administered at least twice, first two cycles of drug delivery accompanied with PK analyses.

Group Type: EXPERIMENTAL

JK-1201I

Intervention Type: DRUG

malignant solid tumor that has been confirmed by histopathology and/or cytology

150mg/m2

Fifth dose level, administered at least twice, first two cycles of drug delivery accompanied with PK analyses.

Group Type: EXPERIMENTAL

JK-1201I

Intervention Type: DRUG

malignant solid tumor that has been confirmed by histopathology and/or cytology

180mg/m2

Sixth dose level, administered at least twice, first two cycles of drug delivery accompanied with PK analyses.

Group Type: EXPERIMENTAL

JK-1201I

Intervention Type: DRUG

malignant solid tumor that has been confirmed by histopathology and/or cytology

175mg/m2

CPT-11, given every 14 days, first 2 cycles of drug delivery will accompanied with PK test,

Group Type: ACTIVE_COMPARATOR

JK-1201I

Intervention Type: DRUG

malignant solid tumor that has been confirmed by histopathology and/or cytology

Interventions

JK-1201I

malignant solid tumor that has been confirmed by histopathology and/or cytology

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 18 to 70 years of age (inclusive)；

2. Body mass index (BMI) within the range of 19-30 (inclusive)

3. Patient with a malignant solid tumor that has been confirmed by histopathology and/or cytology to be ineffective in conventional treatment or lack effective treatment。 Primary tumors include colorectal cancer, gastric cancer, esophageal cancer, pancreatic cancer and advanced breast cancer patients with brain metastases

4. More than 4 weeks after the completion of previous anti-tumor therapy (including chemotherapy/radiotherapy, surgical treatment, targeted therapy, immunotherapy, Chinese herbal medicine therapy, endocrine therapy or other anti-tumor therapy), And it has recovered from the adverse reactions of previous treatments (treatment-related toxicity grade ≤1);

5. At least one measurable or evaluable lesion was identified using RECIST 1.1;

6. Physical state score (ECOG PS score) 0~1

7. Estimated survival time ≥ 3 months

8. Both standard blood tests and Blood Biochemistry tests are within normal range.

9. All subjects and their partners have no plan to have children from screening to 6 month after the trial, and those who agree to use effective non-drug contraceptive methods during the trial period (e.g., condoms， etc.), those already have permanent contraceptive measures, such as bilateral tubal ligation, vasectomy, etc.

10. Voluntarily participate in clinical research and sign informed consent

Exclusion Criteria

1. Patients with previous allergy history and known severe allergy to injectable PEG-Irinotecan or any excipient of the product;

2. Have received HCl-Irinotecan (CPY-11) treatment in the past

3. With active brain metastasis;

4. Have other malignant tumors within 5 years before enrollment, except for previously treated with the purpose of radical cure such as carcinoma in situ of the cervix, squamous cell carcinoma or basal cell carcinoma

5. Large amount of thorax and ascites that need treatment

6. Serious cardiovascular disease, including grade II and above cardiac dysfunction (NYHA standard)

7. Active hepatitis b (HBsAg and/or HBCAb positive, peripheral blood HBV DNA titer test ≥1×103 IU/mL, or hepatitis c patients; or testing positive for syphilis or human immunodeficiency virus (HIV);

8. Subject is participating in other clinical studies or the presumed first time of drug administration is less than 4 weeks from the end of the previous clinical study (last administration or 5 half-lives of the previous study drug);

9. Subjects who have been treated with anti-tumor vaccines or other anti-tumor drugs (interferon, interleukin, etc.) with immune-stimulatory effects within 28 days before the assumed first medication

10. Subjects who had a severe infection within 4 weeks before the first medication， including but not limited to complications of infection, bacteremia, severe pneumonia and others requiring hospital stays;

11. Patient has electrolyte disorder with clinically significance

12. Subject has clinically severe gastrointestinal disorders, (positive fecal occult blood with severe gastrointestinal bleeding, gastrointestinal infection, obstruction or diarrhea of grade 1 or above on endoscopic examination (the number of stool increases ≥4 times per day))

13. Patients with bleeding tendency or receiving thrombolytic or anticoagulant therapy

14. Within 14 days before receiving the study drug treatment subject have used a strong CYP3A4 inducer (Phenytoin or Carbamazepine, Barbiturates, Rifampicin or Rifabutin, Hypericum perforatum, etc.);

15. Within 7 days prior drug treatment, patients have used strong CYP3A4 inhibitors (Clarithromycin, Ketoconazole or Itraconazole, Indinavir, Lopinavir, Nafazodone, Nelfinavir, Ritonavir, Saquinavir, Trapavir, Voriconazole, etc.)

16. Within 7 days before receiving study drug treatment, subject has used strong UGT1A1 inhibitors (Atazanavir, Gemfibrozil, etc.)

17. Clear history of neuropathy or mental disorders (including epilepsy or dementia)

18. Persons with a history of alcohol or drug abuse

19. Pregnant or lactating women

20. Investigator considered the subject who are not suitable to participate in this study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

JenKem Technology Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xuan Zhao, Ph.D.

Role: STUDY_CHAIR

JenKem Technology Co., Ltd.

Locations

The fifth medical center of PLA general hospital

Beijing, Beijing Municipality, China

Countries

China

Other Identifiers

JK-1201I-P1

Identifier Type: -

Identifier Source: org_study_id