HIPEC After Secondary Cytoreductive Operation in Patients With Platinum-sensitive Recurrence of Ovarian Carcinoma (HIPEC)
Primary Purpose
Epithelial Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Cancer
Status
Withdrawn
Phase
Phase 2
Locations
Austria
Study Type
Interventional
Intervention
HIPEC
Carboplatin
Sponsored by
About this trial
This is an interventional treatment trial for Epithelial Ovarian Cancer
Eligibility Criteria
Inclusion Criteria:
- ≥18 years
- Signed informed consent
- Patients with platinum-sensitive recurrence after 12-48 months after platinum-based firstline-chemotherapy of histological saved epithelial ovarian carcinoma, primary peritoneal carcinoma or tube carcinoma with planned cytoreductive operation
- The following histological types can be included: serous, endometrioide, clear cell or undifferentiated carcinoma. Mixed epithelial carcinoma, malignant Brenner Tumour
- No preceding recurrence chemotherapy
- Preceding hormontherapy admitted. Concomitant antineoplastic antihormone-therapy (Tamoxifen, Aromataseinhibitoren etc.) not admitted. Low dosed (physiological) hormone-replacement-therapie (HRT) can be administered
- Patients with maintenance therapy (e.g. Bevacizumab) permitted, assumed recurrence was diagnosed 12 months after primary cytotoxic chemotherapy (also with maintenancetherapy during chemotherapy) and last administration of maintenancetherapy happened min. 21 days before first study protocol intervention
- Resectability R0 probably, fixed by Desktop II-criteria:
- Cytoreductive operation at first-diagnosis of the carcinoma R0
- Ascites <500 ml
- ECOG 0
- R0 status (≤0,5 cm tumour rest) at the end of secondary cytoreductive operation
- Eligibility for Standard systemic platinum-based combination chemotherapy after sec. cytoreductive operation with or without HIPEC (investigators decision)
- Bone marrow function: Haemoglobine ≥8.5 g/dL, Absol. neutrophile Granulocytes(ANC) ≥1.000/mm3, Thrombocytes ≥ 100.000/mm3
- Renal function: Serum Creatinin ≤1,5 times the ULN, calculated Creatininclearance (GFR) ≥60ml/min
- Liver function: Bilirubin ≤1,5 x
- ALT, AST ≤3 x ULN
- Adequate coagulation parameter: INR-value ≤1,5, aPTT ≤1,5 x ULN
- For patients under fully-dosed/therapeutic Warfarin- or Phenprocoumontherapy INR between 2-3 and aPTT <1,2 x ULN
- Neurol. Function: peripheral Neuropathy ≤Grade 2 (CTCAE v4.03 criteria)
- In women with childbearing potential availability of a neg. serum pregnancy test 2 weeks before planned sec. cytored. operation + effective contraception during study period guaranteed
Exclusion Criteria:
- No signed informed consent
- Tumours with low malignant potential (Borderline-carzinomas)
- Patients with preceding radiotherapy in abdomen and pelvis
- Patients with preceding endometrial carcinoma will be excluded, except: Stage IA [no low differentiated subtype (serous-papillary, clear cellular, FIGO grade 3)]
- With the exception of non-melanoma skin cancer and other specific malignancies as noted above, subjects with other invasive malignancies, who had any evidence of the other cancer present within the last 3 years or whose previous cancer treatment contraindicates this protocol therapy, are excluded
- Known acute hepatitis
- acute infectious disease with need for intravenous antibiosis
- immunodeficiency
- Active coronaryarterial disease: Myocardinfarct or instable Angina pectoris within 6 months before study inclusion: coronary artery disease in anamnesis can be included, assumed a normal stress-electrocardiogram finding within 30 days before study inclusion
- Cardiac insufficiency NYHA ≥2 classif. of New York Heart Association
- Hypertension ≥140/90 mm Hg
- Poorly controlled cardiac arrythmia despite medication (patients with frequencey-controlled atrial fibrillation can participate)
- Peripheral vascular disease ≥grade 3 (e.g. symptomatic and affecting activities of everyday-life, intervention or revision necessary)
- Renal insufficiency Serumcreatininvalues ≥1,5 times the ULN or GFR <60ml/min
- Cerebrovascular disease in anamnesis
- Patients with another severe medical problem-independent of cancer-which excludes study participation
- Known allergies to Carboplatin or Cisplatin
- extended intraperitoneal adhesions at time of secondary cytoreductive operation, which makes administration of intraperitioneal chemotherapy impossible
- Life expectancy <12 weeks
Sites / Locations
- Department of gynaecology, Ordensklinikum Linz Ges.m.b.H, Barmherzige Schwestern
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
HIPEC
Arm Description
If patient is eligible - secondary cytoreductive operation will be followed by HIPEC with 800 mg/m² body surface (KOF) Carboplatin with closed technique.
Outcomes
Primary Outcome Measures
Elevation of side-effects and postoperative complication-rate
Observation, classification and graduation of side-effects through NCI Common Terminology Criteria for Adverse Events version 4.03 ["safety issue"]
Secondary Outcome Measures
Survey of quality of life per EORTC evaluated questionnaires
Using EORTC -QLQ-C30 and EORTC QLQ-OV28, at study initiation, postoperative, before systemic chemotherapy and afterwards
Recording of PFS (progession free survival)
Recording of PFS (progession free survival) of the patients in a time-span of 24 months [kein "safety issue"]
Full Information
NCT ID
NCT02487849
First Posted
June 13, 2015
Last Updated
March 2, 2020
Sponsor
Krankenhaus Barmherzige Schwestern Linz
1. Study Identification
Unique Protocol Identification Number
NCT02487849
Brief Title
HIPEC After Secondary Cytoreductive Operation in Patients With Platinum-sensitive Recurrence of Ovarian Carcinoma
Acronym
HIPEC
Official Title
Feasability of an Unique Intraoperative Given Hyperthermal Intraperitoneal Chemotherapy With Carboplatin During a Secondary Cytoreductive Operation in Patients With Platinum-sensitive Recurrence of Ovarian Carcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Withdrawn
Why Stopped
actually limited personnel ressources
Study Start Date
August 2016 (Actual)
Primary Completion Date
August 2016 (Actual)
Study Completion Date
August 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Krankenhaus Barmherzige Schwestern Linz
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
The combination of optimal cytoreductive operation (according to Desktop II criteria), HIPEC with Carboplatin 800 mg/m² KOF (Körperoberfläche) and following platinum-based systemic chemotherapy should be executed In patients with platinum-sensitive recurrence of ovarian carcinoma. Condition for HIPEC is attainment of optimal cytoreduction (R0) and experts judgement of a complication-free prolongation of narcosis after finishing the surgery. HIPEC will be administered additionally to standard therapy. If HIPEC was executed the number of systemic given platinum-based chemotherapy decreases for one cycle.
This regime should be investigated in terms of safety of performance, quality of life for the patients and consequences for the following systemic chemotherapy.
Detailed Description
In occurence with a platinum-sensitive recurrence of EOC survival can be prolonged by a recurrence-operation, if macroscopical tumor-free status (optimal cytoreductive operation) can be reached in combination with a platinum-based standard-chemotherapy.
Several studies showed that the combination of optimal cytoreductive operation and HIPEC is a secure method of treatment. In comparison to operation and standard-chemotherapy it has a significant positive influence on survival rates. A hyperthermal intraperitoneal chemotherapy with Carboplatin is possible without severe side-effects.
The combination of optimal cytoreductive operation (according to Desktop II criteria), HIPEC with Carboplatin and following platinum-based systemic chemotherapy should be carried out in patients with platinum-sensitive recurrence.
Condition for applying HIPEC is reaching optimal cytoreduction (<0.5 cm visible tumour rest at the end of operation) and according to expert opinion a complicatin-free prolongation of narcosis after finishing the operative intervention. HIPEC is carried out additionally to standard therapy. If it can be carried out, the amount of systemically administered patinum-based chemotherapy is reduced for one cycle.
This regime should be tested on safety in performance, quality of life for patients, and consequences for the following systemic chemotherapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epithelial Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HIPEC
Arm Type
Experimental
Arm Description
If patient is eligible - secondary cytoreductive operation will be followed by HIPEC with 800 mg/m² body surface (KOF) Carboplatin with closed technique.
Intervention Type
Procedure
Intervention Name(s)
HIPEC
Other Intervention Name(s)
Hyperthermal intraperitoneal Chemotherapy
Intervention Description
secondary cytoreductive operation
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Carboplatin Accord
Intervention Description
Hyperthermal Intraperitoneal Chemotherapy (HIPEC)
Primary Outcome Measure Information:
Title
Elevation of side-effects and postoperative complication-rate
Description
Observation, classification and graduation of side-effects through NCI Common Terminology Criteria for Adverse Events version 4.03 ["safety issue"]
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Survey of quality of life per EORTC evaluated questionnaires
Description
Using EORTC -QLQ-C30 and EORTC QLQ-OV28, at study initiation, postoperative, before systemic chemotherapy and afterwards
Time Frame
24 months
Title
Recording of PFS (progession free survival)
Description
Recording of PFS (progession free survival) of the patients in a time-span of 24 months [kein "safety issue"]
Time Frame
24 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
≥18 years
Signed informed consent
Patients with platinum-sensitive recurrence after 12-48 months after platinum-based firstline-chemotherapy of histological saved epithelial ovarian carcinoma, primary peritoneal carcinoma or tube carcinoma with planned cytoreductive operation
The following histological types can be included: serous, endometrioide, clear cell or undifferentiated carcinoma. Mixed epithelial carcinoma, malignant Brenner Tumour
No preceding recurrence chemotherapy
Preceding hormontherapy admitted. Concomitant antineoplastic antihormone-therapy (Tamoxifen, Aromataseinhibitoren etc.) not admitted. Low dosed (physiological) hormone-replacement-therapie (HRT) can be administered
Patients with maintenance therapy (e.g. Bevacizumab) permitted, assumed recurrence was diagnosed 12 months after primary cytotoxic chemotherapy (also with maintenancetherapy during chemotherapy) and last administration of maintenancetherapy happened min. 21 days before first study protocol intervention
Resectability R0 probably, fixed by Desktop II-criteria:
Cytoreductive operation at first-diagnosis of the carcinoma R0
Ascites <500 ml
ECOG 0
R0 status (≤0,5 cm tumour rest) at the end of secondary cytoreductive operation
Eligibility for Standard systemic platinum-based combination chemotherapy after sec. cytoreductive operation with or without HIPEC (investigators decision)
Bone marrow function: Haemoglobine ≥8.5 g/dL, Absol. neutrophile Granulocytes(ANC) ≥1.000/mm3, Thrombocytes ≥ 100.000/mm3
Renal function: Serum Creatinin ≤1,5 times the ULN, calculated Creatininclearance (GFR) ≥60ml/min
Liver function: Bilirubin ≤1,5 x
ALT, AST ≤3 x ULN
Adequate coagulation parameter: INR-value ≤1,5, aPTT ≤1,5 x ULN
For patients under fully-dosed/therapeutic Warfarin- or Phenprocoumontherapy INR between 2-3 and aPTT <1,2 x ULN
Neurol. Function: peripheral Neuropathy ≤Grade 2 (CTCAE v4.03 criteria)
In women with childbearing potential availability of a neg. serum pregnancy test 2 weeks before planned sec. cytored. operation + effective contraception during study period guaranteed
Exclusion Criteria:
No signed informed consent
Tumours with low malignant potential (Borderline-carzinomas)
Patients with preceding radiotherapy in abdomen and pelvis
Patients with preceding endometrial carcinoma will be excluded, except: Stage IA [no low differentiated subtype (serous-papillary, clear cellular, FIGO grade 3)]
With the exception of non-melanoma skin cancer and other specific malignancies as noted above, subjects with other invasive malignancies, who had any evidence of the other cancer present within the last 3 years or whose previous cancer treatment contraindicates this protocol therapy, are excluded
Known acute hepatitis
acute infectious disease with need for intravenous antibiosis
immunodeficiency
Active coronaryarterial disease: Myocardinfarct or instable Angina pectoris within 6 months before study inclusion: coronary artery disease in anamnesis can be included, assumed a normal stress-electrocardiogram finding within 30 days before study inclusion
Cardiac insufficiency NYHA ≥2 classif. of New York Heart Association
Hypertension ≥140/90 mm Hg
Poorly controlled cardiac arrythmia despite medication (patients with frequencey-controlled atrial fibrillation can participate)
Peripheral vascular disease ≥grade 3 (e.g. symptomatic and affecting activities of everyday-life, intervention or revision necessary)
Renal insufficiency Serumcreatininvalues ≥1,5 times the ULN or GFR <60ml/min
Cerebrovascular disease in anamnesis
Patients with another severe medical problem-independent of cancer-which excludes study participation
Known allergies to Carboplatin or Cisplatin
extended intraperitoneal adhesions at time of secondary cytoreductive operation, which makes administration of intraperitioneal chemotherapy impossible
Life expectancy <12 weeks
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lukas Hefler, Prim. Dr.
Organizational Affiliation
Krankenhaus der Barmherzigen Schwestern Linz
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of gynaecology, Ordensklinikum Linz Ges.m.b.H, Barmherzige Schwestern
City
Linz
ZIP/Postal Code
4010
Country
Austria
12. IPD Sharing Statement
Learn more about this trial
HIPEC After Secondary Cytoreductive Operation in Patients With Platinum-sensitive Recurrence of Ovarian Carcinoma
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