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

NCT04366648 | Completed Phase 1

• 1 other identifier: JK-1201I-P1
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Primary outcome 1

  Maximum tolerance dose (MTD) will be determined. MTD is defined as the highest dose that can be given without causing any adverse side effects according to CTCAE v5.0. The dose climbing scheme was designed according to the improved Fibonacci method, which was carried out in sequence from the low dose group to the high dose group. The principle of "3+3" dose increment was adopted. At least 4 subjects were randomly enrolled in each dose group (including one patient who will be assigned to control drug).

  21 days

• Primary outcome 2

  Dose limited toxicity (DLT) of injectable PEG -Irinotecan in patients will be determined. DLT is defined as: 1..Grade 4 neutropenia (ANC) reduction lasts ≥3 days; or grade 3 ANC reduction with fever (ANC \<1000 / mm3 with oral temperature single measurement\> 38.3 ℃ or ≥38.0 ℃ for 1 hour)； 2. Grade 3 thrombocytopenia (25×109/L≤ platelet count \< 50×109/L) with obvious clinical bleeding symptoms, or grade 4 thrombocytopenia (with or without obvious clinical bleeding symptoms); 3. Other grade 4 hematological toxicity； 4. Grade 3 and above non-hematological toxicity； 5. Hair loss, fatigue, except for those with grade 3 nausea, vomiting, and diarrhea without maximum symptomatic supportive treatment.

  21 days

Secondary Outcomes (2)

• Secondary outcome 1

  21 days

• Secondary outcome 2

  21 days

Study Arms (7)

50mg/m2

EXPERIMENTAL

Starting dose, administered once only

Drug: JK-1201I

75mg/m2

EXPERIMENTAL

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

Drug: JK-1201I

100mg/m2

EXPERIMENTAL

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

Drug: JK-1201I

125mg/m2

EXPERIMENTAL

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

Drug: JK-1201I

150mg/m2

EXPERIMENTAL

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

Drug: JK-1201I

180mg/m2

EXPERIMENTAL

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

Drug: JK-1201I

175mg/m2

ACTIVE COMPARATOR

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

Drug: JK-1201I

Interventions

JK-1201I DRUG

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

100mg/m2; 125mg/m2; 150mg/m2; 175mg/m2; 180mg/m2; 50mg/m2; 75mg/m2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 70 years of age (inclusive)；
• Body mass index (BMI) within the range of 19-30 (inclusive)
• 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
• 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);
• At least one measurable or evaluable lesion was identified using RECIST 1.1;
• Physical state score (ECOG PS score) 0\~1
• Estimated survival time ≥ 3 months
• Both standard blood tests and Blood Biochemistry tests are within normal range.
• 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.
• Voluntarily participate in clinical research and sign informed consent

You may not qualify if:

• Patients with previous allergy history and known severe allergy to injectable PEG-Irinotecan or any excipient of the product;
• Have received HCl-Irinotecan (CPY-11) treatment in the past
• With active brain metastasis;
• 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
• Large amount of thorax and ascites that need treatment
• Serious cardiovascular disease, including grade II and above cardiac dysfunction (NYHA standard)
• 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);
• 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);
• 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
• 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;
• Patient has electrolyte disorder with clinically significance
• 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))
• Patients with bleeding tendency or receiving thrombolytic or anticoagulant therapy
• 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.);
• 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.)

Sponsors & Collaborators

• JenKem Technology Co., Ltd.: lead

Study Sites (1)

The fifth medical center of PLA general hospital

Beijing, Beijing Municipality, 100071, China

Location

Study Officials

• Xuan Zhao, Ph.D.

  JenKem Technology Co., Ltd.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study is a multicenter, open labled, positive controled, single, -combined, with multiple dose escalation trial.

Study Record Dates

• First Submitted: April 8, 2020
• First Posted: April 29, 2020
• Study Start: May 4, 2018
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: September 4, 2024

Record last verified: 2024-08

Locations

CN (1)