Short-course HIPEC in Advanced Epithelial Ovarian Cancer

Conditions

Ovarian Cancer

Keywords

Ovarian Cancer

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.

ROBERTO JOSÉ COSTA LUSTOSA, Thales Paulo Batista, Vandré Cabral Gomes Carneiro, Levon Badiglian‐Filho, Ronaldo Lúcio Rangel Costa et al. (10 authors)

Revista do Colégio Brasileiro de Cirurgiões2020-01-018 citations

10.1590/0100-6991e-20202534

388 Short-course HIPEC at the time of interval debulking surgery for high tumor burden ovarian cancer: preliminary results of a pioneering clinical trial in brazil

Thales Paulo Batista, Vandré Cabral Gomes Carneiro, Rodrigo Tancredi, Levon Badiglian‐Filho, Bruno José Queiroz Sarmento et al. (10 authors)

2019-09-01

10.1136/ijgc-2019-igcs.388

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.

Batista TP, Carneiro VCG, Tancredi R, Teles ALB, Badiglian-Filho L, Leão CS.

2017-12-139 citations

10.2147/cmar.s153327

Exploring flow rate selection in HIPEC procedures

Thales Paulo Batista, Levon Badiglian‐Filho, Cristiano de Souza Leão

Revista do Colégio Brasileiro de Cirurgiões2016-12-017 citations

10.1590/0100-69912016006014

Papers published before 2007-09-01 may not appear yet. Historical indexing is in progress.

Interventions

PROCEDURECytoreductive Surgery (CRS)

CRS was performed with standard peritonectomy procedures and visceral resections directed towards complete elimination of tumors from the abdominopelvic cavity.

PROCEDUREHyperthermic 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.

DRUGNeoadjuvant 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.

DRUGAdjuvant 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.

PROCEDUREFast-track recovery strategy

A comprehensive fast-track program was applied to accelerate recovery, reduce morbidity, and shorten convalescence for patients enrolled in our trial.

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

No

Inclusion 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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Postoperative 30-day mortality rate	30 days	Mortality rates up to 30-day after surgery
Postoperative complication rates	30 days	Complications rates up to 30-day after surgery
Assessment of quality of life (QLQ-C30/EORTC)	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.
Progression-free Survival (PFS)	24 months	We defined PFS as the time from starting the NACT to disease progression.
Disease-free Survival (DFS)	24 months	We defined DFS for patients without no gross residual disease as the time from IDS plus HIPEC to disease progression.
Overall survival (OS)	24 months	We defined OS as the time from starting the NACT to death.

Other

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

Outcome results

None listed