Phase 3 Trial Evaluating Hyperthermic Intraperitoneal Chemotherapy in Upfront Treatment of Stage IIIC Epithelial Ovarian Cancer

Ovarian Neoplasms Clinical Trial

— CHORINE  

Official title:

Stage IIIC Unresectable Epithelial Ovarian/Tubal Cancer With Partial or Complete Response After 1st Line Neoadjuvant Chemotherapy (3 Cycles CBDCA+Paclitaxel): a Phase 3 Prospective Randomized Study Comparing Cytoreductive Surgery + Hyperthermic Intraperitoneal Chemotherapy (CDDP+Paclitaxel) + 3 Cycles CBDCA+Paclitaxel vs Cytoreductive Surgery Alone + 3 Cycles CBDCA+Paclitaxel.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01628380
• Other study ID #: CHORINE 2012-002616-22
• Status: Recruiting
• Phase: Phase 3
• First received: June 22, 2012
• Last updated: August 27, 2014
• Start date: June 2012
• Est. completion date: July 2018

Study information

• Verified date: August 2014
• Source: A.O. Ospedale Papa Giovanni XXIII
• Contact: Luca Ansaloni, MD
• Phone: +390352673477
• Email: lansaloni[@]hpg23.it
• Is FDA regulated: No
• Health authority: Italy: CLIOSSItaly: Ethics Committee Ospedali Riuniti di Bergamo
• Study type: Interventional

Clinical Trial Summary

Aim of the Study is to compare two-years disease-free survival of Cytoreductive Surgery (CRS) and Hyperthermic IntraPEritoneal Chemotherapy (HIPEC, CDDP+Paclitaxel) vs CRS alone in Stage IIIC unresectable epithelial tubal/ovarian cancer with partial or complete response after 3 cycles of 1st line chemotherapy (CBDCA +Paclitaxel).

Description:

Eligible: Female adult women (18 to 70 years old) patients, with epithelial ovarian/tubal (FIGO stage IIIC) with a Fagotti modified Laparoscopic Scoring System ≥ 4 who will show a complete or partial clinical response(RECIST 1.1) after 3 cycles of neoadjuvant chemotherapy (Carboplatin+Paclitaxel).

Duration of recruitment: 2 years. Sample size has been calculated to reach a confidence level of 95% with a power of 80%, considering a 45% and 75% disease-free survival at 2 years in CRS and CRS+HIPEC group respectively.

Sample size will be 47 patients for each group. After CRS, only patients with adequate cytoreduction (CC 0-1, residual tumor ≤ 2.5mm) will be randomized. Patients with suboptimal cytoreduction (CC 2-3, residual tumor > 2.5mm) are not suitable for randomization.

The drug schedule elected in the current study is Cisplatin (CDDP) (100 mg/m2 of body surface area) + Paclitaxel (175mg/m2 of body surface area).

Closed/open technique, as preferred. Duration: 90 minutes. Mean Intra-abdominal Temperature:

42°C. Primary Endpoint: 2-years disease-free survival.

Secondary Endpoints:

1-year, 3- and 5-years disease-free survival;

1 month, 1-year, 3- and 5-years overall survival; toxicity induced by HIPEC using the NCI CTC criteria; one month and six months morbidity; duration of operation; return of bowel function; length of hospital stay; return to normal activity; six months and one year QOL, using the SF-36 v1.0; percentage of patients in both arms completing the scheduled postoperative chemotherapy; Subgroup analysis: PCI ≤ 15; pts. ≤ 40yrs.

Main topics of this Study:

Focused only on upfront treatment of primary disease. Select platinum-sensible patients (responders to platinum-based neoadjuvant chemotherapy).

Take advantage of NACT to maximize chances for cytoreduction. Standardized strategy for CRS:

radical surgery, associated to any surgical procedure needed to obtain a zero or ≤ 0.25cm residual tumor (peritonectomy, bowel resection, diaphragmatic stripping, gastric resection, etc.). Pelvic and peri-aortic lymphadenectomy is not chosen as standard procedure, but should warrant adequate staging.

Compare only the effect of HIPEC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 94
• Est. completion date: July 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Female adult women (18 to 70 years old) patients, with EOC (FIGO stage IIIc) with a Fagotti modified Laparoscopic Scoring System = 4 who will show a complete clinical response (cCR) or partial clinical response (cPR) after 3 cycles (Carboplatin+Paclitaxel) of neoadjuvant chemotherapy;

• performance status (ECOG) 0, 1 or 2;

• signed informed consent.

Exclusion Criteria:

• refusing to sign an informed consent;

• age > 70 years and age <18 years;

• BMI > 35;

• impossibility of an adequate follow-up;

• presence of other active neoplasms;

• active infection or other concurrent medical condition that could interfere in the ability of patients to receive the proposed treatment according to protocol;

• extraabdominal metastases (Stage IV) ;

• performance status (ECOG)>2;

• complete bowel obstruction;

• Abnormal bone marrow indices or renal and liver function;

• ASA IV or V.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Neoplasms

Intervention

Procedure:
• Cytoreductive Surgery and HIPEC
CRS: radical surgery, associated to any surgical procedure needed to obtain a zero or = 0.25cm residual tumor (peritonectomy, bowel resection, diaphragmatic stripping, gastric resection, etc.). HIPEC: Cisplatin (CDDP) (100 mg/m2 of body surface area) + Paclitaxel (175mg/m2 of body surface area). Closed/open technique, as preferred. Duration: 90 minutes. Mean Intra-abdominal Temperature: 42°C.
• CRS alone
CRS: radical surgery, associated to any surgical procedure needed to obtain a zero or = 0.25cm residual tumor (peritonectomy, bowel resection, diaphragmatic stripping, gastric resection, etc.)

Locations

Country	Name	City	State
Germany	Jena University Hospital	Jena
Italy	A.O. Papa Giovanni XXIII (former Ospedali Riuniti)	Bergamo	Bg
Italy	A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna - Bologna (Bo)	Bologna	Bo
Italy	A.O. Universitaria Di Parma - Parma (Pr) Oncologia Chirurgica	Parma	Pr
Italy	POLICLINICO UNIVERSITARIO GEMELLI DI ROMA - ROMA (RM) GINECOLOGIA E OSTETRICIA Dipartimento per la Tutela della Salute della Donna e della Vita Nascente	Roma

Sponsors (3)

Lead Sponsor	Collaborator
A.O. Ospedale Papa Giovanni XXIII	Clinical Organization for Strategies & Solutions (CLIOSS), former Nerviano Medical Sciences (http://www.nervianoms.com/en/), Onlus Cancro Primo Aiuto (http://www.cpaonlus.it/)

Countries where clinical trial is conducted

Germany,  Italy, 

References & Publications (1)

Ansaloni L, De Iaco P, Frigerio L. Re: "cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as upfront therapy for advanced epithelial ovarian cancer: multi-institutional phase II trial." - Proposal of a clinical trial of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in advanced ovarian cancer, the CHORINE study. Gynecol Oncol. 2012 Apr;125(1):279-81. doi: 10.1016/j.ygyno.2012.01.001. Epub 2012 Jan 9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease free survival		2 years	No
Secondary	postoperative morbidity and mortality		1 and 6 months	Yes
Secondary	Time to Chemotherapy	percentage of patients in both arms completing the scheduled postoperative chemotherapy and time elapsed to start postoperative chemotherapy	3 months	No
Secondary	Overall Survival		1, 3 and 5 years	No