A Dose-finding Trial of Hyperthermic Intraperitoneal Docetaxel

A Dose-finding Trial of Hyperthermic Intraperitoneal Docetaxel and Cisplatin in Patients Receiving Hyperthermic Intraperitoneal Chemotherapy

This is a single-center study design, and 30 patients will be enrolled. Eligible patients will receive docetaxel at different dose levels according to the trial schedule.All the enrolled patients were treated with docetaxel during the first HIPEC treatment and cisplatin during the second HIPEC treatment at 43℃ for 1 hour.The dose of docetaxel for patients in the next group was determined according to the incidence of dose-limiting toxicity (DLT) of the previous docetaxel dose level. Finally, the maximum tolerated dose (MTD) of docetaxel for HIPEC was calculated according to the incidence of dose-limiting toxicity.

Study Overview

• Status: Recruiting
• Conditions: Hyperthermic Intraperitoneal Chemotherapy
• Intervention / Treatment: Drug: Docetaxel

Detailed Description

This is a single-center study design, and 30 patients will be enrolled. Eligible patients will receive docetaxel at different dose levels according to the trial schedule. All the enrolled patients were treated with docetaxel during the first HIPEC treatment and cisplatin during the second HIPEC treatment at 43℃ for 1 hour. Four dosages of docetaxel were set up in the study. We decided to take the initial dose of 60mg/m2 and increase the remaining dose gradient by 5 mg/m2. The dosage of cisplatin was 75mg/m2. Time-to-event Bayesian Optimal Interval Design(TITE-BOIN) was used, with 3 patients as an observation group (i.e. a cohort), starting from a dose of 60mg/m2. The dose of docetaxel for patients in the next group was determined according to the incidence of dose-limiting toxicity (DLT) of the previous docetaxel dose level. Finally, the maximum tolerated dose (MTD) of docetaxel for HIPEC was calculated according to the incidence of dose-limiting toxicity.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: miaofang Wu; Phone Number: +8613828494674; Email: wmiaofang@mail.sysu.edu.cn
• Study Contact Backup: Name: Zhiyao You; Phone Number: +8613725368618; Email: youzhy3@mail2.sysu.edu.cn

Study Locations

• China
  • Other (Non U.s.)
    • Guangzhou, Other (Non U.s.), China, 510000
      • Recruiting
      • Sun Yat-sen Memorial Hospital
      • Contact: miaofang Wu; Phone Number: +8613828494674; Email: wmiaofang@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. According to the gynecology malignant tumor abdominal hot perfusion chemotherapy clinical expert consensus, with HIPEC treatment indications, including the initial treatment of ovarian cancer, recurrent ovarian cancer, peritoneum pseudo myxoma, accompanied by abdominal cavity effusion or disseminated other gynecological malignant tumors of peritoneal cavity transfer, branch caused by malignant tumors refractory peritoneal effusion, Uterine sarcoma found after the use of tumor (uterine) device, ovarian mucous tumor before or during the rupture, a large amount of mucus overflow contamination of the abdominal cavity.
2. Ages 18 to 70.
3. Serum creatinine was within the normal range (reference range of creatinine: 58-96μmol/L) before receiving HIPEC, and renal function was normal.
4. No bone marrow suppression before HIPEC (considering many factors affecting hemoglobin level, including intraoperative blood loss and postoperative fluid infusion hemodilution, hemoglobin ≥80g/L was set; Leukocyte ≥ 4.0*109/L, granulocyte ≥ 2.0×109/L; Platelet ≥ 100×109/L).
5. No abnormal liver function before receiving HIPEC (total bilirubin 3.4-22.2μmol/L, ALT 7-40 U/L, AST 13-35U/L, AST/ALT≤1.5).
6. Signed informed consent and received docetaxel and cisplatin HIPEC treatment.

Exclusion Criteria:

1. Contraindications to HIPEC: intestinal obstruction; Extensive adhesion in peritoneal cavity; The abdominal cavity has obvious inflammation; There may be high risk factors for poor postoperative anastomotic healing, including anastomotic tissue edema, ischemia, obvious tension, severe hypoproteinemia, etc. Dysfunction of major organs such as heart, kidneys, liver and brain; Severe coagulopathy; Bile obstruction and ureteral obstruction.
2. No history of radiotherapy or chemotherapy in recent 3 weeks.
3. In addition to HIPEC, docetaxel and cisplatin should be used by other means within 3 weeks after HIPEC treatment.
4. Those who have taken drugs that damage liver and kidney function or inhibit bone marrow within 3 months.
5. Allergic to docetaxel and cisplatin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Docetaxel dose level; Initial dose of 60mg/m2 and increase the remaining dose gradient by 5 mg/m2	Drug: Docetaxel; Hyperthermic Intraperitoneal Docetaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose of docetaxel	The MTD of docetaxel for abdominal thermal perfusion was calculated by observing the incidence of dose-limiting toxicity 3 weeks after the end of HIPEC.	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of DLT	Number of DLT cases at current dose/total cases at current dose	9 weeks
Effect of dose on tumor control rate	The decrease of serum CA125 and HE4 concentrations and the results of imaging evaluation at different doses of docetaxel	9 weeks

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Principal Investigator: Zhongqiu Lin, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): February 1, 2023

Study Registration Dates

• First Submitted: May 31, 2022
• First Submitted That Met QC Criteria: June 6, 2022
• First Posted (Actual): June 8, 2022

Study Record Updates

• Last Update Posted (Actual): June 8, 2022
• Last Update Submitted That Met QC Criteria: June 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Hyperthermia; Fever; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: 2022-KY-061

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: After data publication

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No