Short-course HIPEC in Advanced Epithelial Ovarian Cancer

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02249013
• Other study ID #: U1111-1158-0472
• Secondary ID: 18388113.4.0000.
• Status: Completed
• Phase: Phase 2
• Start date: February 2015
• Est. completion date: February 23, 2021

Study information

• Verified date: March 2021
• Source: Professor Fernando Figueira Integral Medicine Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: February 23, 2021
• Est. primary completion date: February 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

• 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.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Procedure:
• Cytoreductive Surgery (CRS)
CRS was performed with standard peritonectomy procedures and visceral resections directed towards complete elimination of tumors from the abdominopelvic cavity.
• 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.
• 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.

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.

Locations

Country	Name	City	State
n/a

Sponsors (7)

Lead Sponsor	Collaborator
Professor Fernando Figueira Integral Medicine Institute	AC Camargo Cancer Center (São Paulo/SP), Hospital de Base do Distrito Federal (Brasilia/DF), Hospital de Cancer de Barretos - Fundacao Pio XII (Barretos/SP), Hospital de Câncer de Pernambuco (Recife/PE), Hospital Sao Jose (Criciuma/SC), Instituto Brasileiro de Controle do Câncer (São Paulo/SP)

References & Publications (3)

Batista TP, Badiglian Filho L, Leão CS. Exploring flow rate selection in HIPEC procedures. Rev Col Bras Cir. 2016 Dec;43(6):476-479. doi: 10.1590/0100-69912016006014. Portuguese, English. — View Citation

Batista TP, Carneiro VCG, Tancredi R, Teles ALB, Badiglian-Filho L, Leão CS. Neoadjuvant chemotherapy followed by fast-track cytoreductive surgery plus short-course hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer: preliminary — View Citation

Lustosa RJC, Batista TP, Carneiro VCG, Badiglian-Filho L, Costa RLR, Lopes A, Sarmento BJQ, Lima JTO, Mello MJG, LeÃo CS. Quality of life in a phase 2 trial of short-course hyperthermic intraperitoneal chemotherapy (HIPEC) at interval debulking surgery fo — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to start chemotherapy after surgery	Time to start adjuvant chemotherapy after surgery (CRS).	An expected range of 4 to 8 weeks
Other	Length of ICU and hospital stay	Length of ICU and hospital stay.	An expected range of 5 to 30 days
Primary	PD9	Proportion of patients with disease progression or death occurring within 9 months of IDS plus HIPEC	9 months
Secondary	Postoperative 30-day mortality rate	Mortality rates up to 30-day after surgery	30 days
Secondary	Postoperative complication rates	Complications rates up to 30-day after surgery	30 days
Secondary	Assessment of quality of life (QLQ-C30/EORTC)	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
Secondary	Overall survival (OS)	We defined OS as the time from starting the NACT to death.	24 months
Secondary	Progression-free Survival (PFS)	We defined PFS as the time from starting the NACT to disease progression.	24 months
Secondary	Disease-free Survival (DFS)	We defined DFS for patients without no gross residual disease as the time from IDS plus HIPEC to disease progression.	24 months

External Links

•   A technical note exploring the dynamic relationships between flow rates and temperature parameters in the first cases of our study.
•   The first paper describing early outcomes and insights after an interim analysis of our pioneering clinical trial in Brazil