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HIPEC in Ovarian Carcinoma Clinical Stage IIIC and IV During Interval Laparotomy

Primary Purpose

HPEC, Ovarian Cancer, Women's Health: Neoplasm of Ovary

Status
Recruiting
Phase
Phase 2
Locations
Mexico
Study Type
Interventional
Intervention
HIPEC
Sponsored by
Instituto Nacional de Cancerologia de Mexico
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HPEC

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients younger than 70 years
  2. Patient with a diagnosis of high grade serous carcinoma of the ovary and low-grade endometrioid corroborated by histopathological study.
  3. Clinical stage IIIC and IVA (cytology-positive pleural effusion) who have received induction chemotherapy 3 or 4 cycles of CARBOPLATIN and PACLITAXEL.
  4. Partial response to treatment with chemotherapy and evaluated by computed tomography (RECIST-see below) and response of at least 50% by serum determination of CA-125 antigen.
  5. Signature of informed consent.
  6. Optimal cytoreduction with residual tumor less than 2.5 mm during interval surgery
  7. ECOG less than or equal to 1
  8. Adequate renal, cardiac, hepatic, bone marrow and lung function evaluated preoperatively with the following parameters:

    a) Hb equal to or greater than 10 g / L (pre-treatment transfusion is permitted to achieve this hemoglobin level) b) Leukocytes Greater than 3000 / mm3 (c) Platelets equal to or greater than 100 000 / mm3 (d) total bilirubin less than 1.5 times greater than the normal value e) Hepatic transaminases less than 1.5 times higher than normal value f) Creatinine <1.2 g / dl. In case of being elevated the measured purification should be greater than 60mL / min according to Cockroft's formula.

    g) Albumin greater than 3gr / dl. h) Left Ventricle Ejection fraction per cardiac echography greater than 55% 9). Sugarbaker carcinomatosis index less than 20

Exclusion Criteria:

  1. Patients with heart failure, ischemic heart disease
  2. Previous history of treatment with chemotherapy for some other neoplasia
  3. History of neuropsychiatric disease
  4. Patients with intra operative bleeding that condition hemodynamic instability.
  5. Patient requiring more than 2 intraoperative anastomosis

Sites / Locations

  • National Cancer Institute of MexicoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Control group

HIPEC group

Arm Description

After achieving a complete cytoreductive surgery (no visible residual disease), the patient will be randomised and if is assigned to this arm does not receive additional treatment and the procedure will be finished.

After achieving a complete cytoreductive surgery (no visible residual disease), the patient will be randomised and if is assigned to this arm receive a HIPEC procedure with cisplatin and doxorubicin.

Outcomes

Primary Outcome Measures

Mortality
To assess the mortality associated with the use of intraperitoneal hyperthermic chemotherapy during interval laparotomy.
Impact of quality of life
To evaluate the impact on patients' quality of life, which is undergoing intraperitoneal hyperthermic chemotherapy during interval laparotomy. The scales that will be used will be EORTC QLQ-C30 (Ver. 3) and EORTC QLQ-OV28.
Morbility
To assess the morbidity associated with the use of intraperitoneal hyperthermic chemotherapy during interval laparotomy.

Secondary Outcome Measures

Disease free survival
Evaluate disease-free survival.
Overall survival
Evaluate overall 5 year survival.

Full Information

First Posted
September 2, 2017
Last Updated
April 26, 2023
Sponsor
Instituto Nacional de Cancerologia de Mexico
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1. Study Identification

Unique Protocol Identification Number
NCT03275194
Brief Title
HIPEC in Ovarian Carcinoma Clinical Stage IIIC and IV During Interval Laparotomy
Official Title
Hyperthermic Intraperitoneal Chemotherapy in Ovarian Carcinoma Clinical Stage IIIC and IV During Interval Laparotomy. Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 2, 2017 (Actual)
Primary Completion Date
December 1, 2025 (Anticipated)
Study Completion Date
December 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Instituto Nacional de Cancerologia de Mexico

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Ovarian cancer is the leading cause of gynecological cancer mortality, with no current screening method effective for early diagnosis, with 75% of advanced stage patients being detected. Not all patients are candidates for standard treatment, which is primary cytoreduction followed by adjuvant chemotherapy, due to the advanced process. A subgroup of patients will receive neoadjuvant chemotherapy followed by interval surgery, which allows higher rates of optimal cytoreduction with low morbidity and mortality. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a therapeutic option that is used in pathologies of peritoneal dissemination, whose morbidity and mortality has been reported in several series and is promising as a management option for ovarian cancer, so it is necessary to evaluate morbidity and mortality that conditions this modality of treatment as well as if it impacts on the quality of life of the patients to whom they are performed, which will allow offering our patients an option of additional treatment to the standard.
Detailed Description
Ovarian cancer ranks seventh in incidence of malignant neoplasms in women younger than 65 years and is the leading cause of cancer death in women in the United States. Due to the absence of an effective screening method and early symptoms, 70% of the cases are diagnosed in advanced clinical stage (stage III or IV) and the overall 5-year survival is 30-40%. The standard treatment of locally advanced ovarian carcinoma is primary cytoreductive surgery plus adjuvant chemotherapy with carboplatin and taxanes. In cases where it is not possible to perform primary cytoreductive surgery a treatment option is to start with induction chemotherapy (three or four cycles), in order to reduce tumor size and volume, after which it is performed an interval surgery, during which it has been reported that optimal cytoreduction is achieved in 77-94% of patients, with lower morbidity and mortality than primary surgery, without oncological compromise. Subsequent to interval surgery three additional cycles of chemotherapy are applied. Despite an adequate response to the treatment aforementioned, 70% of patients will recur within the first two years. Because of this high recurrence rate, other therapeutic alternatives have been evaluated, among them is hyperthermic intraperitoneal chemotherapy (HIPEC). Since its first description 20 years ago, the HIPEC associated with cytoreductive surgery in the treatment of malignant neoplasms (primary or metastatic) in the peritoneal surface has become the standard of treatment, specifically in patients with peritoneal pseudomyxoma, peritoneal mesothelioma, and cancer with limited peritoneal involvement. In ovarian cancer, attempts are being made to determine its usefulness in specific scenarios of this disease. The increasing interest in the use of HIPEC in the management of advanced ovarian cancer is based on the coelomic dissemination of ovarian cancer, which in theory would allow this modality of treatment to be effective. Moreover, optimal cytoreduction and administration of intraperitoneal chemotherapy over intravenous (intraperitoneal normothermy) have been shown to be superior in achieving higher survival rates in randomised trials. Few groups in the world have studied the use of HIPEC in ovarian cancer, however, studies have been (and are being conducted) in the following scenarios: a) during primary cytoreduction, b) during interval laparotomy, c) as consolidation after standard treatment, d) recurrence of platinum resistant carcinoma and e) in the recurrence of "platinum sensitive" carcinoma. The morbidity of this procedure reported in different series is 33-39%, and mortality of 0-9%. The feasibility of the procedure with low rates of morbidity and mortality has been reported, specially when the treatment is done by a multidisciplinary group especially trained in HIPEC. The present project is a Phase II, randomised study whose primary objective is to evaluate the morbidity, mortality, and quality of life of patients undergoing HIPEC during the surgery with optimal surgical cytoreduction. One group will be treated with cytoreduction and adjuvant chemotherapy, while the experimental group will be treated with cytoreduction followed by HIPEC. Our secondary objectives are the assessment of the disease-free period and overall survival. The working hypothesis is that the use of HIPEC during interval surgery will have a morbidity considered as acceptable as reported in the literature without significant deterioration in the quality of life. The importance of evaluating this new therapeutic tool is that any of the current treatments for ovarian cancer have a high rate of recurrence. Based in the evidence, biological behaviour and pattern of dissemination of ovarian cancer, treatment should incorporate both systemic and locoregional therapy, because the neoplasm spreads via coelomic, lymphatic and hematogenous. The use of HIPEC together with the surgical event of cytoreduction could avoid recurrence and allow us to distinguish those patients who are candidates for this procedure and their actual benefit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HPEC, Ovarian Cancer, Women's Health: Neoplasm of Ovary, Chemotherapy Effect

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
The data will be evaluated for a external person with the groups labeled as "A" and "B" for all outcomes.
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control group
Arm Type
No Intervention
Arm Description
After achieving a complete cytoreductive surgery (no visible residual disease), the patient will be randomised and if is assigned to this arm does not receive additional treatment and the procedure will be finished.
Arm Title
HIPEC group
Arm Type
Experimental
Arm Description
After achieving a complete cytoreductive surgery (no visible residual disease), the patient will be randomised and if is assigned to this arm receive a HIPEC procedure with cisplatin and doxorubicin.
Intervention Type
Procedure
Intervention Name(s)
HIPEC
Intervention Description
Following complete cytoreductive surgery without any evidence of residual disease, the patient will be randomized either HIPEC (intervention) or no-HIPEC (control) in the operative Room. If the arm HIPEC is obtained, then a HIPEC procedure with cisplatin and doxorubicin will be performed. If no-HIPEC (control arm) is assigned then the surgical procedure will be finished.
Primary Outcome Measure Information:
Title
Mortality
Description
To assess the mortality associated with the use of intraperitoneal hyperthermic chemotherapy during interval laparotomy.
Time Frame
Up to 1 year
Title
Impact of quality of life
Description
To evaluate the impact on patients' quality of life, which is undergoing intraperitoneal hyperthermic chemotherapy during interval laparotomy. The scales that will be used will be EORTC QLQ-C30 (Ver. 3) and EORTC QLQ-OV28.
Time Frame
Up to 1 year
Title
Morbility
Description
To assess the morbidity associated with the use of intraperitoneal hyperthermic chemotherapy during interval laparotomy.
Time Frame
Up to 1 year
Secondary Outcome Measure Information:
Title
Disease free survival
Description
Evaluate disease-free survival.
Time Frame
Up to 2 years
Title
Overall survival
Description
Evaluate overall 5 year survival.
Time Frame
up to five years

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Genotypic sex
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients younger than 70 years Patient with a diagnosis of high grade serous carcinoma of the ovary and low-grade endometrioid corroborated by histopathological study. Clinical stage IIIC and IVA (cytology-positive pleural effusion) who have received induction chemotherapy 3 or 4 cycles of CARBOPLATIN and PACLITAXEL. Partial response to treatment with chemotherapy and evaluated by computed tomography (RECIST-see below) and response of at least 50% by serum determination of CA-125 antigen. Signature of informed consent. Optimal cytoreduction with residual tumor less than 2.5 mm during interval surgery ECOG less than or equal to 1 Adequate renal, cardiac, hepatic, bone marrow and lung function evaluated preoperatively with the following parameters: a) Hb equal to or greater than 10 g / L (pre-treatment transfusion is permitted to achieve this hemoglobin level) b) Leukocytes Greater than 3000 / mm3 (c) Platelets equal to or greater than 100 000 / mm3 (d) total bilirubin less than 1.5 times greater than the normal value e) Hepatic transaminases less than 1.5 times higher than normal value f) Creatinine <1.2 g / dl. In case of being elevated the measured purification should be greater than 60mL / min according to Cockroft's formula. g) Albumin greater than 3gr / dl. h) Left Ventricle Ejection fraction per cardiac echography greater than 55% 9). Sugarbaker carcinomatosis index less than 20 Exclusion Criteria: Patients with heart failure, ischemic heart disease Previous history of treatment with chemotherapy for some other neoplasia History of neuropsychiatric disease Patients with intra operative bleeding that condition hemodynamic instability. Patient requiring more than 2 intraoperative anastomosis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rosa A Salcedo-Hernandez, MSc
Organizational Affiliation
Instituto Nacional de Cancerologia, Columbia
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cancer Institute of Mexico
City
Mexico City
ZIP/Postal Code
14080
Country
Mexico
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rosa A Salcedo-Hernández, M.Sc
Phone
525534265921
Email
rosasalher@gmail.com
First Name & Middle Initial & Last Name & Degree
Leonardo S Lino-Silva
Phone
525534265921
Email
saul.lino.sil@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
The database without any patient identity data could be accede for anyone asking for.

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HIPEC in Ovarian Carcinoma Clinical Stage IIIC and IV During Interval Laparotomy

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