Clinical trial NCT02249013: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Ovarian Cancer
Lead sponsor: Professor Fernando Figueira Integral Medicine Institute
Sponsor class: OTHER
Collaborators: name: Hospital de Câncer de Pernambuco (Recife/PE)
name: AC Camargo Cancer Center (São Paulo/SP)
name: Instituto Brasileiro de Controle do Câncer (São Paulo/SP)
name: Hospital de Cancer de Barretos - Fundacao Pio XII (Barretos/SP)
name: Hospital Sao Jose (Criciuma/SC)
name: Hospital de Base do Distrito Federal (Brasilia/DF)
First posted: 2014-09-25
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: PD9
timeFrame: 9 months
Secondary outcomes:
measure: Postoperative 30-day mortality rate
timeFrame: 30 days
measure: Postoperative complication rates
timeFrame: 30 days
measure: Assessment of quality of life (QLQ-C30/EORTC)
timeFrame: 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
measure: Overall survival (OS)
timeFrame: 24 months
measure: Progression-free Survival (PFS)
timeFrame: 24 months
measure: Disease-free Survival (DFS)
timeFrame: 24 months
Other outcomes:
measure: Time to start chemotherapy after surgery
timeFrame: An expected range of 4 to 8 weeks
measure: Length of ICU and hospital stay
timeFrame: An expected range of 5 to 30 days
Locations:
Study officials:
affiliation: Professor Fernando Figueira Integral Medicine Institute
name: Thales P Batista, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.