Short-course HIPEC in Advanced Epithelial Ovarian Cancer
Primary Purpose
Ovarian Cancer
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Cytoreductive Surgery (CRS)
Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Neoadjuvant Chemotherapy (NACT)
Adjuvant Chemotherapy
Fast-track recovery strategy
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer focused on measuring Ovarian Cancer
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
HIPEC
Arm Description
Neoadjuvant Chemotherapy (NACT) followed by Cytoreductive Surgery (CRS) under a Fast-track recovery strategy plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and thus, Adjuvant Chemotherapy
Outcomes
Primary Outcome Measures
PD9
Proportion of patients with disease progression or death occurring within 9 months of IDS plus HIPEC
Secondary Outcome Measures
Postoperative 30-day mortality rate
Mortality rates up to 30-day after surgery
Postoperative complication rates
Complications rates up to 30-day after surgery
Assessment of quality of life (QLQ-C30/EORTC)
Assessment of quality of life according to the QLQ-C30/EORTC scales.
Overall survival (OS)
We defined OS as the time from starting the NACT to death.
Progression-free Survival (PFS)
We defined PFS as the time from starting the NACT to disease progression.
Disease-free Survival (DFS)
We defined DFS for patients without no gross residual disease as the time from IDS plus HIPEC to disease progression.
Full Information
NCT ID
NCT02249013
First Posted
September 22, 2014
Last Updated
March 17, 2021
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)
1. Study Identification
Unique Protocol Identification Number
NCT02249013
Brief Title
Short-course HIPEC in Advanced Epithelial Ovarian Cancer
Official Title
Short-course Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at Interval Debulking Surgery for High Tumor Burden Ovarian Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
February 2015 (Actual)
Primary Completion Date
February 23, 2021 (Actual)
Study Completion Date
February 23, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the 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)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
Ovarian Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HIPEC
Arm Type
Experimental
Arm Description
Neoadjuvant Chemotherapy (NACT) followed by Cytoreductive Surgery (CRS) under a Fast-track recovery strategy plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and thus, Adjuvant Chemotherapy
Intervention Type
Procedure
Intervention Name(s)
Cytoreductive Surgery (CRS)
Intervention Description
CRS was performed with standard peritonectomy procedures and visceral resections directed towards complete elimination of tumors from the abdominopelvic cavity.
Intervention Type
Procedure
Intervention Name(s)
Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Neoadjuvant Chemotherapy (NACT)
Other Intervention Name(s)
Carboplatin, Paclitaxel
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Adjuvant Chemotherapy
Other Intervention Name(s)
Carboplatin, Paclitaxel
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Fast-track recovery strategy
Intervention Description
A comprehensive fast-track program was applied to accelerate recovery, reduce morbidity, and shorten convalescence for patients enrolled in our trial.
Primary Outcome Measure Information:
Title
PD9
Description
Proportion of patients with disease progression or death occurring within 9 months of IDS plus HIPEC
Time Frame
9 months
Secondary Outcome Measure Information:
Title
Postoperative 30-day mortality rate
Description
Mortality rates up to 30-day after surgery
Time Frame
30 days
Title
Postoperative complication rates
Description
Complications rates up to 30-day after surgery
Time Frame
30 days
Title
Assessment of quality of life (QLQ-C30/EORTC)
Description
Assessment of quality of life according to the QLQ-C30/EORTC scales.
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
Title
Overall survival (OS)
Description
We defined OS as the time from starting the NACT to death.
Time Frame
24 months
Title
Progression-free Survival (PFS)
Description
We defined PFS as the time from starting the NACT to disease progression.
Time Frame
24 months
Title
Disease-free Survival (DFS)
Description
We defined DFS for patients without no gross residual disease as the time from IDS plus HIPEC to disease progression.
Time Frame
24 months
Other Pre-specified Outcome Measures:
Title
Time to start chemotherapy after surgery
Description
Time to start adjuvant chemotherapy after surgery (CRS).
Time Frame
An expected range of 4 to 8 weeks
Title
Length of ICU and hospital stay
Description
Length of ICU and hospital stay.
Time Frame
An expected range of 5 to 30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thales P Batista, MD, MS
Organizational Affiliation
Professor Fernando Figueira Integral Medicine Institute
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
We have no plan to make individual participant data (IPD) available to other researchers.
Citations:
PubMed Identifier
29263704
Citation
Batista TP, Carneiro VCG, Tancredi R, Teles ALB, Badiglian-Filho L, Leao CS. Neoadjuvant chemotherapy followed by fast-track cytoreductive surgery plus short-course hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer: preliminary results of a promising all-in-one approach. Cancer Manag Res. 2017 Dec 13;9:869-878. doi: 10.2147/CMAR.S153327. eCollection 2017.
Results Reference
result
PubMed Identifier
28273222
Citation
Batista TP, Badiglian Filho L, Leao CS. Exploring flow rate selection in HIPEC procedures. Rev Col Bras Cir. 2016 Dec;43(6):476-479. doi: 10.1590/0100-69912016006014. English, Portuguese.
Results Reference
result
PubMed Identifier
32667582
Citation
Lustosa RJC, Batista TP, Carneiro VCG, Badiglian-Filho L, Costa RLR, Lopes A, Sarmento BJQ, Lima JTO, Mello MJG, LeAo CS. Quality of life in a phase 2 trial of short-course hyperthermic intraperitoneal chemotherapy (HIPEC) at interval debulking surgery for high tumor burden ovarian cancer. Rev Col Bras Cir. 2020;47:e20202534. doi: 10.1590/0100-6991e-20202534. Epub 2020 Jul 10. English, Portuguese.
Results Reference
result
Links:
URL
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732565/
Description
The first paper describing early outcomes and insights after an interim analysis of our pioneering clinical trial in Brazil
URL
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-69912016000600476&lng=en&nrm=iso&tlng=en
Description
A technical note exploring the dynamic relationships between flow rates and temperature parameters in the first cases of our study.
Learn more about this trial
Short-course HIPEC in Advanced Epithelial Ovarian Cancer
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