Short-course HIPEC in Advanced Epithelial Ovarian Cancer

March 17, 2021 updated by: Thales Paulo Batista, Professor Fernando Figueira Integral Medicine Institute

Short-course Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at Interval Debulking Surgery for High Tumor Burden Ovarian Cancer

This is an open-label, multicenter, single-arm, feasibility phase 2 trial on safety and efficacy of short-course regimen of intra-operative Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at the time of fast-track interval debulking surgery (IDS) following neoadjuvant chemotherapy (NACT) for high tumor burden epithelial ovarian cancer (EOC).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study was initially designed to explore the safety and efficacy of short-course HIPEC in terms of median progression-free survival (PFS) as the primary outcome. However, due to slow accrual, the design was subsequently amended to explore the primary outcome measure of PD9 (i.e.: proportion of patients with disease progression or death occurring within 9 months of IDS plus HIPEC). The hypothesis was the short-course HIPEC could decrease PD9 with low rates of morbidity and mortality. In these settings, we explore a comprehensive treatment approach involving fast-track advanced cytoreductive surgery (CRS) plus short-course HIPEC at the time of IDS following NACT for high tumor burden patients with stage III-IV ovarian cancer. Advanced CRS was performed with standard peritonectomy procedures and visceral resections directed towards complete elimination of tumors from the abdominopelvic cavity, and fast-track recovery strategies were also applied to improve patient outcomes. HIPEC was performed according to the closed-abdomen technique using CDDP (25 mg/L of perfusate/m2, total limit of 240mg) or CDDP plus Doxorubicin (15mg/L) for 30 minutes, with an intra-abdominal target temperature of 41-43°C. Perfusate (2L/m2, ranging from 4L to 6L) was circulated using an extracorporeal circulation device (Performer HT; RAND, Medolla, Italy) at a flow rate of 700 ml/min. Systemic chemotherapy included the standard combination of carboplatin and paclitaxel as neo-adjuvant plus adjuvant regimens.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • Inclusion Criteria:

    • Patients with no previous treatment and candidates for elective surgery with histological diagnosis of epithelial ovarian carcinoma;
    • Clinical stage IIIB to IV, without suspicion of extra-abdominal metastasis;
    • No other malignancies in activity;
    • No previous treatments such as radiation, chemotherapy (except neoadjuvant chemotherapy in the study protocol) or major abdominal surgery;
    • Absence of neuro-psychiatric disorders, history of drug allergies, and pregnancy or breast feeding;
    • Aged between 18 and 70 years;
    • Performance status 0-2 (ECOG, Eastern Cooperative Oncology Group) and / or greater than 70 points by the Karnofsky scale;
    • Appropriated cardio-respiratory, hepato-renal and hematological reserves;
    • Signing of the Consent Form.

  • Exclusion Criteria:

    • Evidence of extensive retroperitoneal lymph node involvement or unresectable disease (i.e., massive involvement of the small bowel, mesentery, or hepatic pedicle, and ureteral or biliary obstruction) at the time of CRS/HIPEC;
    • Residual disease after the CRS greater than or equal to 2.5 mm (CC-2 and CC-3);
    • Limiting obesity for CRS or HIPEC;
    • Disease progression, apparent or confirmed uncontrolled infection, or health impairment during NACT.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HIPEC
Neoadjuvant Chemotherapy (NACT) followed by Cytoreductive Surgery (CRS) under a Fast-track recovery strategy plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and thus, Adjuvant Chemotherapy
Procedure: Cytoreductive Surgery (CRS)
CRS was performed with standard peritonectomy procedures and visceral resections directed towards complete elimination of tumors from the abdominopelvic cavity.
Procedure: Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
HIPEC was performed according to the closed-abdomen technique using CDDP (25 mg/L of perfusate/m2, total limit of 240mg) for the first 10 patients and thus, using CDDP plus Doxorubicin (15mg/L) thereafter, both for 30 minutes, with an intra-abdominal target temperature of 41-43°C. Perfusate (2L/m2, ranging from 4L to 6L) was circulated using an extracorporeal circulation device (Performer HT; RAND, Medolla, Italy) at a flow rate of 700 ml/min.
Drug: Neoadjuvant Chemotherapy (NACT)
Systemic chemotherapy included the standard combination of carboplatin (AUC 6) and paclitaxel (175 mg/m2) administered every 21 days as neoadjuvant (2-4 cycles) plus adjuvant regimens (2-4 cycles), in the total of 6 cycles of systemic chemotherapy.
Other Names:
  • Carboplatin
  • Paclitaxel
Drug: Adjuvant Chemotherapy
Systemic chemotherapy included the standard combination of carboplatin (AUC 6) and paclitaxel (175 mg/m2) administered every 21 days as neoadjuvant (2-4 cycles) plus adjuvant regimens (2-4 cycles), in the total of 6 cycles of systemic chemotherapy.
Other Names:
  • Carboplatin
  • Paclitaxel
Procedure: Fast-track recovery strategy
A comprehensive fast-track program was applied to accelerate recovery, reduce morbidity, and shorten convalescence for patients enrolled in our trial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PD9
Time Frame: 9 months
Proportion of patients with disease progression or death occurring within 9 months of IDS plus HIPEC
9 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Postoperative 30-day mortality rate
Time Frame: 30 days
Mortality rates up to 30-day after surgery
30 days
Postoperative complication rates
Time Frame: 30 days
Complications rates up to 30-day after surgery
30 days
Assessment of quality of life (QLQ-C30/EORTC)
Time Frame: Baseline (i.e., at the time of hospital admission for IDS plus HIPEC); after CRS/HIPEC (i.e., at the time of restarting the systemic chemotherapy); after protocol (i.e., at 3-6 weeks after the last syst
Assessment of quality of life according to the QLQ-C30/EORTC scales.
Baseline (i.e., at the time of hospital admission for IDS plus HIPEC); after CRS/HIPEC (i.e., at the time of restarting the systemic chemotherapy); after protocol (i.e., at 3-6 weeks after the last syst
Overall survival (OS)
Time Frame: 24 months
We defined OS as the time from starting the NACT to death.
24 months
Progression-free Survival (PFS)
Time Frame: 24 months
We defined PFS as the time from starting the NACT to disease progression.
24 months
Disease-free Survival (DFS)
Time Frame: 24 months
We defined DFS for patients without no gross residual disease as the time from IDS plus HIPEC to disease progression.
24 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to start chemotherapy after surgery
Time Frame: An expected range of 4 to 8 weeks
Time to start adjuvant chemotherapy after surgery (CRS).
An expected range of 4 to 8 weeks
Length of ICU and hospital stay
Time Frame: An expected range of 5 to 30 days
Length of ICU and hospital stay.
An expected range of 5 to 30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Professor Fernando Figueira Integral Medicine Institute

Collaborators

Hospital de Câncer de Pernambuco (Recife/PE)
AC Camargo Cancer Center (São Paulo/SP)
Instituto Brasileiro de Controle do Câncer (São Paulo/SP)
Hospital de Cancer de Barretos - Fundacao Pio XII (Barretos/SP)
Hospital Sao Jose (Criciuma/SC)
Hospital de Base do Distrito Federal (Brasilia/DF)

Investigators

  • Principal Investigator: Thales P Batista, MD, MS, Professor Fernando Figueira Integral Medicine Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2015

Primary Completion (Actual)

February 23, 2021

Study Completion (Actual)

February 23, 2021

Study Registration Dates

First Submitted

September 22, 2014

First Submitted That Met QC Criteria

September 23, 2014

First Posted (Estimate)

September 25, 2014

Study Record Updates

Last Update Posted (Actual)

March 18, 2021

Last Update Submitted That Met QC Criteria

March 17, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • U1111-1158-0472
  • 18388113.4.0000.5201 (Other Identifier: CAAE)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

We have no plan to make individual participant data (IPD) available to other researchers.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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