Irinotecan Liposome，Albumin Paclitaxel and Gemcitabine First-line Treatment for Pancreatic Cancer

Irinotecan Liposome Combined With Albumin Paclitaxel and Gemcitabine as First-line Treatment for Locally Advanced or Metastatic Pancreatic Cancer

This is a Phase I/II , Open-label , Investigator-initiated Trail of liposomal irinotecan,nab-paclitaxel and gemcitabine as First-line Treatment in Advanced pancreatic cancer. The study was designed in two stages, the first stage was the tolerance observation stage, and the second stage was the curative effect expansion stage.

The first part of the study is the Dose-finding Phase designed to establish the safety of nab-paclitaxel，gemcitabine and liposomal irinotecan at different dose Levels(40 mg/m2, iv. q2w or 60 mg/m2, iv. q2w). The second part of the study is the Expansion Phase designed to generate additional clinical data at specified doses .

This study aims to evaluate the safety and efficacy of liposomal irinotecan，nab-paclitaxel and gemcitabine in the First-line treatment of advanced pancreatic cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Irinotecan liposome（40mg/m2）; Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Irinotecan Liposome（60mg/m2）

Detailed Description

The study consists of a dose escalation and expansion phase to determine the recommended Phase 2 dose (RP2D) for liposomal irinotecan combination with AG, and a dose confirmation phase which will further characterize the treatment of liposomal irinotecan in combination at the RP2D.

• Study Type: Interventional
• Enrollment (Estimated): 132
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yanqiao Zhang, PhD; Phone Number: +86 138 4512 0210; Email: yanqiaozhang@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: 18 to 75 years old, male or female;
2. Patients with pancreatic cancer diagnosed by histology or cytology;
3. Not received anti-tumor system treatment (if received neoadjuvant or adjuvant therapy, need to ensure that the last time is more than 6 months)；
4. With measurable tumor lesions (spiral CT scan ≥10mm, meet RECIST 1.1 standard);
5. ECOG PS: 0-1 points;
6. Expected survival time> 3 months;

7. The functions of important organs meet the following requirements:

   1. Absolute neutrophil count ≥1.5×109/L, platelet ≥100×109/L, hemoglobin ≥9g/dL;
   2. Bilirubin ≤ 1.5 times ULN (patients drained by retrograde technique may be included); ALT and AST ≤ 3 times ULN;
   3. Creatinine ≤ 1.5 times, or MDRD creatinine clearance rate> 50 mL/min;
8. Women of childbearing age must undergo a negative pregnancy test (βHCG) before starting treatment. Women and men of childbearing age (sexual relationships with women of childbearing age) must agree to use them effectively during treatment and 6 months after the last dose of treatment Contraceptive measures;
9. Signature of patient information and informed consent.

Exclusion Criteria:

1. Previous allergy to irinotecan liposome, other liposome products, fluorouracil and other therapeutic drugs;
2. previous or concurrent history of other malignant tumors, except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix;
3. Participated in other drug clinical trials within 4 weeks before randomization;
4. Severe gastrointestinal dysfunction;
5. The presence of third space effusion (e.g., massive pleural effusion) in addition to ascites that could not reach a stable state within 2 weeks before randomization;
6. Peripheral neuropathy (CTCAE≥ grade 3);
7. Patients with a history of bleeding, with any bleeding event of CTCAE 5.0 grade 3 or higher within 4 weeks before screening; Gastrointestinal bleeding of CTCAE grade 3 or higher was reported within 6 months before randomization or within 1 month before randomization；
8. Interstitial lung disease, except interstitial changes only on imaging;
9. Screening patients with known or history of central nervous system metastases;
10. Concomitant medication containing a strong inhibitor/strong inducer of CYP3A4, CYP2C8, or a strong inhibitor of UGT1A1 within 2 weeks before randomization;
11. Severe infection (CTCAE > grade 2) within 4 weeks before treatment; Signs and symptoms of infection requiring treatment with intravenous antibiotics within 2 weeks before the initiation of treatment (except for prophylactic antibiotics);
12. Judging by the researchers, the participants have other factors that could lead to the forced midway termination of research, may affect the participants were given safety or test data collection, etc；
13. Pregnant women or those who expect to become pregnant during the study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; Nab-paclitaxel was administered 125mg/m2 D1、D8、D15，iv. q4w，gemcitabine was administered 1000 mg D1、D8、D15，iv. q4w，irinotecan Liposome was administered 40mg/m2, D1，iv. q2w	Drug: Irinotecan liposome（40mg/m2）; irinotecan Liposome was administered 40mg/m2, D1，iv. q2w; Other Names: Irinotecan Liposome; Drug: Nab-paclitaxel; Nab-paclitaxel was administered 125mg/m2 D1、D8、D15，iv. q4w; Other Names: Albumin Paclitaxel; Drug: Gemcitabine; gemcitabine was administered 1000 mg D1、D8、D15，iv. q4w; Other Names: Gemcitabine injection
Experimental: Cohort B; Nab-paclitaxel was administered 125mg/m2 D1、D8、D15，iv. q4w，gemcitabine was administered 1000 mg D1、D8、D15，iv. q4w，irinotecan Liposome was administered 60mg/m2, D1，iv. q2w	Drug: Nab-paclitaxel; Nab-paclitaxel was administered 125mg/m2 D1、D8、D15，iv. q4w; Other Names: Albumin Paclitaxel; Drug: Gemcitabine; gemcitabine was administered 1000 mg D1、D8、D15，iv. q4w; Other Names: Gemcitabine injection; Drug: Irinotecan Liposome（60mg/m2）; irinotecan Liposome was administered 60mg/m2, D1，iv. q2w; Other Names: Irinotecan Liposome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD /DLT (phase I)	Maximum Tolerated Dose/Dose Limiting Toxicity	Within four weeks after administration
ORR(phase II)	Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free Survival	Defined as the time between signing the informed consent form to the disease progression (according to RECIST v1.1 criteria) or death due to any cause.	1 year
Disease Control Rate	Defined as the proportion of patients who achieved complete response (CR), partial response (PR), and stable disease (SD) according to RECIST v1.1.	6 months
Overall survival	Defined as the time between signing the informed consent form to death due to various causes.	2 years
Incidence of adverse events	Use NCI-CTCAE version 5.0 for classification and grading	6 months

Collaborators and Investigators

• Sponsor: Harbin Medical University
• Investigators: Principal Investigator: Yanqiao Zhang, Zhang, Harbin Medical University Cancer Hosptital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 16, 2024
• First Submitted That Met QC Criteria: July 16, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Actual): July 22, 2024
• Last Update Submitted That Met QC Criteria: July 16, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Irinotecan Liposome
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Paclitaxel; Irinotecan; Albumin-Bound Paclitaxel; Gemcitabine
• Other Study ID Numbers: MA-PC-II-013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No