A Randomized Prospective Trail of HIPEC in Recurrent Ovarian Cancer Patients With HRR Mutation

A Randomized Prospective Trail of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Recurrent Ovarian Cancer Patients With Mutations in Homologous Recombination Repair (HRR) Genes

A phase III prospective study with the primary objective to investigate the benefit of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in ovarian cancer patients with mutations in homologous recombination repair (HRR) genes. The target population for this study is patients with recurrent ovarian, peritoneal or fallopian tube cancers undergoing Cytoreductive Surgery (CRS). Patients will be divided into two groups according to HRR genes mutation, each group will be further divided into two sub-groups with different intervention. Patients in Group A are HRR mutated type, sub-group 1 will undergo CRS plus HIPEC and then go on to receive standard platinum-based combination doublet intravenous chemotherapy, sub-group 2 will undergo CRS and then go on to intravenous chemotherapy. Patients in Group B are HRR wild type, sub-group 3 will undergo CRS plus HIPEC and then go on to receive standard platinum-based combination doublet intravenous chemotherapy, sub-group 4 will undergo CRS and then go on to intravenous chemotherapy. All patients will receive maintenance therapy with Niraparib after primary treatment. Prognostic information will be collected for investigation of survival benefits of patients.

Study Overview

• Status: Recruiting
• Conditions: Ovarian Cancer; Epithelial Ovarian Cancer; Ovarian Cancer, Epithelial; Hyperthermic Intraperitoneal Chemotherapy(HIPEC); Homologous Recombination Repair Gene Mutation
• Intervention / Treatment: Procedure: CRS+HIPEC; Procedure: CRS alone

• Study Type: Interventional
• Enrollment (Anticipated): 280
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hongbing Cai, Doctor; Phone Number: +86-27-67812648; Email: chb2105@163.com
• Study Contact Backup: Name: Zhen Li, Doctor; Phone Number: +86-27-67812648

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430070
      • Recruiting
      • Zhongnan Hospital of Wuhan University
      • Contact: Yuanzhen Zhang, Doctor; Phone Number: +86-27-67812787; Email: znyyll@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• age 18-75
• Karnofsky performance status >50 or World Health Organization performance score < 2
• primary or recurrence ovarian, peritoneal or fallopian tube epithelial cancer; first intra-abdominal recurrence without distant metastasis (including: unique resectable pleural metastasis which are platinum-sensitive; resectable single lymphatic metastasis retroperitoneal or inguinal)
• preoperative platinum-based chemotherapy (carboplatin and paclitaxel, carboplatin and liposomal doxorubicin, gemcitabine, trabectedin or topotecan)
• lesion can be removed completely or residual disease < 0.5 cm
• last chemotherapy finished no more than 12 weeks after surgery
• no hepatic function damage
• white blood cell count ≥3.5*10^9/L; platelet count ≥80*10^9/L; Hemoglobin ≥90g/L
• no contraindication of surgery and anesthesia
• life expectancy ≥ 3 months
• informed consent form signed

Exclusion Criteria:

• age < 18 or >75
• no history of other cancer
• platinum allergy
• distant metastasis
• used anti-angiogenic drug within 8 weeks
• possibility of more than two resection of alimentary canal
• recurrence < 6 months after primary treatment
• histologic type: non epithelial origin
• infection out of control
• follow-up unable to carry on (geographic or psychic)
• cardiac insufficiency or respiratory insufficiency
• has received HIPEC already
• being in other clinical study
• pregnancy or lactation period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HRR mt 1; Patients are HRR mutated type, will undergo CRS plus HIPEC and then go on to receive standard platinum-based combination doublet intravenous chemotherapy.	Procedure: CRS+HIPEC; Patients will undergo only CRS, HIPEC and IVCT.Patients will receive standard platinum-based combination doublet chemotherapy for 6-8 cycles after CRS and then followed by maintenance therapy. A single drug lobaplatin(30mg/m2)will be administered in normal saline via HIPEC and it will be continued for 60 minutes in the hyperthermic phase (41°C-43°C). HIPEC will be performed at the 1st, 3rd and 5th day after CRS. The intravenous chemotherapy(IVCT) will start from 7th-14th day after CRS.
Experimental: HRR mt 2; Patients are HRR mutated type, will undergo CRS and then go on to receive standard platinum-based combination doublet intravenous chemotherapy.	Procedure: CRS alone; Patients will undergo only CRS and IVCT.Patients will receive standard platinum-based combination doublet chemotherapy for 6-8 cycles after CRS and then followed by maintenance therapy.
Experimental: HRR wt 3; Patients are HRR wild type, will undergo CRS plus HIPEC and then go on to receive standard platinum-based combination doublet intravenous chemotherapy.	Procedure: CRS+HIPEC; Patients will undergo only CRS, HIPEC and IVCT.Patients will receive standard platinum-based combination doublet chemotherapy for 6-8 cycles after CRS and then followed by maintenance therapy. A single drug lobaplatin(30mg/m2)will be administered in normal saline via HIPEC and it will be continued for 60 minutes in the hyperthermic phase (41°C-43°C). HIPEC will be performed at the 1st, 3rd and 5th day after CRS. The intravenous chemotherapy(IVCT) will start from 7th-14th day after CRS.
Experimental: HRR wt 4; Patients are HRR wild type, will undergo CRS and then go on to receive standard platinum-based combination doublet intravenous chemotherapy.	Procedure: CRS alone; Patients will undergo only CRS and IVCT.Patients will receive standard platinum-based combination doublet chemotherapy for 6-8 cycles after CRS and then followed by maintenance therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	The progression-free survival interval was the time between diagnosis and evidence of recurrent or progressive disease.	up to 36 months since diagnosis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The overall survival interval was the time between diagnosis and death or last follow-up.	up to 36 months since histological diagnosis
DP9	The 9 months progression-free survival rate was the rate of no evidence of recurrent or progressive disease at the time of 9 months since histological diagnosis.	the 1 day of histological diagnosis and 9 months after
DP12	The 9 months progression-free survival rate was the rate of no evidence of recurrent or progressive disease at the time of 12 months since histological diagnosis.	the 1 day of histological diagnosis and 12 months after
Serious adverse events, SAEs	Serious adverse events occur within 30 days after surgery, measured with CTCAE 4.0	surgery and with in 30 days

Collaborators and Investigators

• Sponsor: CAI Hongbing

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Anticipated): August 30, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: July 12, 2020
• First Submitted That Met QC Criteria: July 15, 2020
• First Posted (Actual): July 16, 2020

Study Record Updates

• Last Update Posted (Actual): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 4, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Epithelial Ovarian Cancer; Homologous Recombination Repair Gene Mutation; hyperthermic intraperitoneal chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Wounds and Injuries; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Body Temperature Changes; Heat Stress Disorders; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Hyperthermia; Fever
• Other Study ID Numbers: 2020107

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