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

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.

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).

Study Overview

• Status: Unknown
• Conditions: Ovarian Neoplasms
• Intervention / Treatment: Procedure: Cytoreductive Surgery and HIPEC; Procedure: CRS alone

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 94
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Luca Ansaloni, MD; Phone Number: +390352673477; Email: lansaloni@hpg23.it
• Study Contact Backup: Name: Marco Lotti, MD; Phone Number: +390352673477; Email: mlotti@hpg23.it

Study Locations

• Germany
  • Jena, Germany, 07743
    • Recruiting
    • Jena University Hospital
    • Contact: Ingo B. Runnebaum, MD, MBA; Email: INGO.RUNNEBAUM@med.uni-jena.de
    • Principal Investigator: Ingo B. Runnebaum, MD, MBA
• Italy
  • Roma, Italy, 00168
    • Recruiting
    • POLICLINICO UNIVERSITARIO GEMELLI DI ROMA - ROMA (RM) GINECOLOGIA E OSTETRICIA Dipartimento per la Tutela della Salute della Donna e della Vita Nascente
    • Principal Investigator: Giovanni Scambia, MD
    • Contact: Giovanni Scambia, MD; Phone Number: +390630156279; Email: clinicaltrials@rm.unicatt.it
  • Bg
    • Bergamo, Bg, Italy, 24128
      • Recruiting
      • A.O. Papa Giovanni XXIII (former Ospedali Riuniti)
      • Principal Investigator: Luca Ansaloni, MD
      • Contact: Luca Ansaloni, MD; Phone Number: +390352673477; Email: lansaloni@hpg23.it
      • Contact: Marco Lotti, MD; Phone Number: +390352673477; Email: mlotti@hpg23.it
  • Bo
    • Bologna, Bo, Italy, 40138
      • Recruiting
      • A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna - Bologna (Bo)
      • Contact: Pierandrea Deiaco, MD; Phone Number: +390516364426; Email: pierandrea.deiaco@aosp.bo.it
      • Principal Investigator: Pierandrea Deiaco, MD
  • Pr
    • Parma, Pr, Italy, 43100
      • Recruiting
      • A.O. Universitaria Di Parma - Parma (Pr) Oncologia Chirurgica
      • Contact: Fausto Catena, MD; Phone Number: +390521703940; Email: faustocatena@gmail.com
      • Principal Investigator: Fausto Catena, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CRS + HIPEC; Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy with CDDP+Paclitaxel	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.
Active Comparator: CRS alone; Cytoreductive Surgery alone	Procedure: 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.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease free survival	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
postoperative morbidity and mortality		1 and 6 months
Time to Chemotherapy	percentage of patients in both arms completing the scheduled postoperative chemotherapy and time elapsed to start postoperative chemotherapy	3 months
Overall Survival		1, 3 and 5 years

Collaborators and Investigators

• Sponsor: A.O. Ospedale Papa Giovanni XXIII
• Collaborators: Clinical Organization for Strategies & Solutions (CLIOSS), former Nerviano Medical Sciences (http://www.nervianoms.com/en/); Onlus Cancro Primo Aiuto (http://www.cpaonlus.it/)
• Investigators: Principal Investigator: Luca Ansaloni, MD, A.O. Ospedale Papa Giovanni XXIII

Publications and helpful links

General Publications

• 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. No abstract available.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): July 1, 2018

Study Registration Dates

• First Submitted: June 22, 2012
• First Submitted That Met QC Criteria: June 22, 2012
• First Posted (Estimate): June 26, 2012

Study Record Updates

• Last Update Posted (Estimate): August 28, 2014
• Last Update Submitted That Met QC Criteria: August 27, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: HIPEC; Ovarian Cancer; Cytoreductive Surgery
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms
• Other Study ID Numbers: CHORINE 2012-002616-22