Ovarian Epithelial CancerPhase 3HIPOVA-01NCT03220932
Cytoreductive Surgery and HIPEC in First or Secondary Platinum-resistant Recurrent Ovarian Epithelial Cancer
A Phase 3 study testing Cytoreductive surgery combined with HIPEC and Chemotherapy and bevacizumab (CT-BEV) in people with Ovarian Epithelial Cancer, run by Hospices Civils de Lyon at 22 sites in France.
Trial summary
With 4,600 new cases in France in 2012, ovarian cancer is the seventh most common cancer in women and the fourth cause of mortality by cancer. Despite a high response rate to initial treatment, most patients will relapse within 2 years. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Ovarian Epithelial Cancer
- What is being tested?
- Cytoreductive surgery combined with HIPEC and Chemotherapy and bevacizumab (CT-BEV)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 132 participants
- Where
- 22 sitesFrance
- Study dates
- 30 Nov 2019to 30 Nov 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed platinum-resistant Epithelial Ovarian Carcinoma (EOC)(clinical recurrence or persistence within 6 months of last treatment);
- White blood cells >3,500/mm3, neutrophils ≥1,500/mm3, platelets ≥100,000/mm3;
- Good renal function: serum creatinine values <1.5 mg/dl, creatinine clearance >60 ml/min;
- Performance Status ≤2, Karnofsky Index ≥70%;
- Serum bilirubin ≤1.5 x Upper limit of normal (UNL) 2 mg/dl;
- Prior ovarian surgery before starting study treatment;
- Covered by a Healthcare System, where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research;
- Signed written informed consent obtained prior to any study-specific screening procedures.
Who cannot join
- Platinum-refractory EOC (i.e progression under platinum containing chemotherapy);
- Any prior malignancy not considered in complete remission for at least 2 years;
- Pregnancy or breastfeeding;
- Untreated central nervous system disease or symptomatic central nervous system metastasis, history or evidence of thrombotic or hemorrhagic disorders within 6 months before first study treatment;
- Uncontrolled hypertension or active clinically significant cardiovascular disease;
- Females of childbearing age not using medically accepted contraceptive measures, as judged by the investigator;
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- Contraindication to any drug contained in the chemotherapy regimen;
- Known contraindication to cisplatin
- Medical, geographical, sociological, psychological or legal conditions that would prevent the patient from completing the study or signing the informed consent;
- Any significant disease which, in the investigator's opinion, excludes the patient from the study;
- Under any administrative or legal supervision.
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
France22 sites
Centre Hospitalier Universitaire Jean Minjoz
Besançon, 25030
Brice PAQUETTE, MD, 381 668 970 ext. +33, bpaquette@chu-besancon.fr
Brice PAQUETTE, MD
Centre Hospitalier Universitaire Jean Minjoz
Besançon, 25030
Fernando BAZAN, MD, 381 479 999 ext. +33, fbazan@chu-besancon.fr
Fernando BAZAN, MD
Centre Oscar Lambret
Lille, 59000
Fabrice NARDUCCI, MD, 32 0295 944 ext. +33, F-Narducci@o-lambret.fr
Fabrice NARDUCCI, MD
CHRU Claude Huriez
Lille, 59067
Clarisse EVENO, MD, 320 445 962 ext. +33, clarisse.eveno@chru-lille.fr
Clarisse EVENO, MD
Centre Léon Bérard
Lyon, 69008
Pierre MEEUS, MD, 478 782 637 ext. +33, pierre.meeus@lyon.unicancer.fr
Pierre MEEUS, MD
Centre Léon Bérard
Lyon, 69008
Isabelle RAY-COQUARD, MD, 478 782 888 ext. +33, isabelle.ray-coquard@lyon.unicancer.fr
Isabelle RAY-COQUARD, MD
Institut du Cancer de Montpellier
Montpellier, 34298
Pierre-Emmanuel COLOMBO, MD, 467 618 501 ext. +33, Pierre-Emmanuel.Colombo@icm.unicancer.fr
Pierre-Emmanuel COLOMBO, MD
Institut du Cancer de Montpellier
Montpellier, 34298
Véronique D'HONDT, MD, 467 613 151 ext. +33, Veronique.Dhondt@icm.unicancer.fr
Véronique D'HONDT, MD
Centre Hospitalier Universitaire L'Archet II
Nice, 06200
Jérôme DELOTTE, MD, 492 035 948 ext. +33, delotte.j@chu-nice.fr
Jérôme DELOTTE, MD
Centre Hospitalier Universitaire L'Archet II
Nice, 06200
Jean Marc BEREDER, MD, 4 92 03 64 86 ext. +33, bereder.jm@chu-nice.fr
Jean Marc BEREDER, MD
Centre Hospitalier Universitaire L'Archet II
Nice, 06200
Delphine OUVRIER, MD, 492 037 777 ext. +33, ouvrier.d@chu-nice.fr
Delphine OUVRIER, MD
Hôpital Européen Georges Pompidou - APHP
Paris, 75015
Fabrice LECURU, MD, 156 093 567 ext. +33, fabrice.lecuru@egp.aphp.fr
Fabrice LECURU, MD
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
Benoit YOU, MD, 478 864 318 ext. +33, benoit.you@chu-lyon.fr
Benoit YOU, MD
Centre Hospitalier Lyon Sud
Pierre-Bénite
Naoual BAKRIN, MD, 478 862 371 ext. +33, naoual.bakrin@chu-lyon.fr
Naoual BAKRIN, MD
Centre Hospitalier Universitaire de Poitiers
Poitiers, 86021
Nadia RABAN, MD, 549 444 444 ext. +33, nadia.raban@chu-poitiers.fr
Nadia RABAN, MD
Centre Hospitalier Universitaire de St Etienne
Saint-Priest-en-Jarez, 42270
Karine ABBOUD, MD, 477 828 337 ext. +33, karine.abboud@chu-st-etienne.fr
Karine ABBOUD, MD
Centre Hospitalier Universitaire de St Etienne
Saint-Priest-en-Jarez, 42270
Céline CHAULEUR, MD, 477 828 287 ext. +33, celine.chauleur@chu-st-etienne.fr
Céline CHAULEUR, MD
Institut de Cancérologie de la Loire
Saint-Priest-en-Jarez, 42270
Romain RIVOIRARD, MD, 477 917 134 ext. +33, romain.rivoirard@icloire.fr
Romain RIVOIRARD, MD
Centre Hospitalier Universitaire Hautepierre
Strasbourg, 67200
Cécile BRIGAND, MD, 388 127 226 ext. +33, cecile.brigand@chru-strasbourg.fr
Cécile BRIGAND, MD
Centre Hospitalier Universitaire Hautepierre
Strasbourg, 67200
Emmanuel KURTZ, MD, 388 128 436 ext. +33, j-emmanuel.kurtz@chru-strasbourg.fr
Emmanuel KURTZ, MD
Centre Hospitalier Universitaire Hautepierre
Strasbourg, 67200
Chérif AKLADIOS, MD, 388 127 492 ext. +33, Cherif.youssef.azer@chru-strasbourg.fr
Chérif AKLADIOS, MD
Institut de Cancérologie de Lorraine - Alexis Vautrin
Vandœuvre-lès-Nancy, 54519
Frédéric MARCHAL, MD, 383 598 451 ext. +33, f.marchal@nancy.unicancer.fr
Frédéric MARCHAL, MD
About this study
Official title: Assessment of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in First or Secondary Platinum-resistant Recurrent Ovarian Epithelial Cancer
With 4,600 new cases in France in 2012, ovarian cancer is the seventh most common cancer in women and the fourth cause of mortality by cancer. Despite a high response rate to initial treatment, most patients will relapse within 2 years. No standard treatment has yet been established for patients with recurrent ovarian cancer.
Most patients with such recurrences are currently treated with new combinations of systemic chemotherapy. A repeated laparotomy with complete cytoreduction is also an option that several authors have used to obtain median survival rates of more than 30 months.
Read more
Twenty five percent of patients experiencing relapse present with platinum-resistant recurrence, occurring less than 6 months after chemotherapy completion. Recently, Pujade et al. showed that adding bevacizumab to chemotherapy significantly improves progression-free survival (PFS) in this subgroup of patients with poor prognoses (16.6 months versus 13.3 months in women treated with chemotherapy alone). Three case control studies have compared systemic chemotherapy and CRS (Cytoreduction Surgery) alone versus CRS plus HIPEC in patients with recurrent disease. They showed significantly improved results with the addition of HIPEC. In the French registry that included 474 patients with recurrence and peritoneal carcinomatosis, the median PFS was 13.8 months for platinum-resistant patients and 13 months for platinum-sensitive patients. Our hypothesis is that surgery would reduce the tumor burden and consequently the number of platinum-resistant tumor clones and that HIPEC would control the microscopic residual disease by increasing the tumor cell cytotoxicity.
We assume that adding a locoregional treatment to an "Aurelia-like" systemic treatment would improve the PFS. We aim to assess the benefit of adding surgery and HIPEC to the treatment of first or second platinum-resistant recurrence compared to chemotherapy + bevacizumab.
- Conditions
- Ovarian Epithelial Cancer
- Being tested
- Cytoreductive surgery combined with HIPEC, Chemotherapy and bevacizumab (CT-BEV)
- Keywords
- Epithelial Ovarian Cancer - Platinum-resistant - Cytoreductive surgery - HIPEC - Quality of Life
- Medical subject headings
- Carcinoma, Ovarian Epithelial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytoreductive surgery combined with HIPECProcedure or surgery
Cytoreductive surgery combined with HIPEC (Cisplatin 70 mg/m2).
Chemotherapy and bevacizumab (CT-BEV)Drug
Chemotherapy and bevacizumab (CT-BEV) 15 mg/kg once every 3 weeks from enrollment until disease progression (RECIST 1.1)
| Study group | Role | What they receive |
|---|---|---|
| Cytoreductive surgery combined with HIPEC | Experimental | All patients will start with three cycles of CT-BEV 15 mg/kg, and will then be randomly. Then one cycle of monochemotherapy without bevacizumab is administered and followed by an interval CRS and HIPEC with postoperative chemotherapy and bevacizumab (CT-BEV - 15 mg/kg once every 3 weeks) until disease progression Receives: Procedure: Cytoreductive surgery combined with HIPEC |
| Aurelia arm | Active comparator | Chemotherapy and bevacizumab (CT-BEV) once every 3 weeks from enrollment until disease progression Receives: Drug: Chemotherapy and bevacizumab (CT-BEV) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Progression will be based on RECIST V1.1 criteria performed on thoraco-abdominopelvic tomodensitometry (TDM ) assessed every 3 months. There is a follow-up period of 36 months.
Measured: Change from baseline to 36 months
Secondary outcomes (4)
Overall survival
There is a follow-up period of 36 months.
Measured: From the randomization to the death or 36 months end of follow-up
Potential treatment-related mortality
Reported only in the experimental arm (cytoreductive surgery + HIPEC)
Measured: During the first 60 postoperative days
Potential treatment-related morbidity
Adverse events (AE) during the follow-up period: safety and tolerability will be assessed in terms of AEs, deaths, laboratory data, and vital signs. AEs will be described using MedDRA terms (version 18.0) and graded according to Common Terminology Criteria for Adverse Events (CTCAE version 5.0). These will be collected for all randomized patients.
Measured: During the first 60 postoperative days
Quality of life assessment
Quality of Life will be assessed using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) for all randomized patients.
Measured: Baseline to 36 months end of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2017
- Study start30 Nov 2019 (estimated)
- Primary completion30 Nov 2022 (estimated)
- Study completion30 Nov 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian Epithelial CancerStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 132 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03220932
- Sponsor's protocol ID
- 69HCL17_0342
- Acronym
- HIPOVA-01
- Status last verified
- Oct 2019
- First submitted
- 11 May 2017
- Last updated
- 1 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in First or Secondary Platinum-resistant Recurrent Ovarian Epithelial Cancer
- ClinicalTrials.gov ID
- NCT03220932
- Acronym / sponsor ID
- HIPOVA-01 / 69HCL17_0342
- Conditions
- Ovarian Epithelial Cancer
- Keywords
- Epithelial Ovarian Cancer - Platinum-resistant - Cytoreductive surgery - HIPEC - Quality of Life
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 132 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 30 Nov 2019 (estimated)
- Primary completion
- 30 Nov 2022 (estimated)
- Study completion
- 30 Nov 2022 (estimated)
- First posted
- 18 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
With 4,600 new cases in France in 2012, ovarian cancer is the seventh most common cancer in women and the fourth cause of mortality by cancer. Despite a high response rate to initial treatment, most patients will relapse within 2 years. No standard treatment has yet been established for patients with recurrent ovarian cancer.
Most patients with such recurrences are currently treated with new combinations of systemic chemotherapy. A repeated laparotomy with complete cytoreduction is also an option that several authors have used to obtain median survival rates of more than 30 months.
Twenty five percent of patients experiencing relapse present with platinum-resistant recurrence, occurring less than 6 months after chemotherapy completion. Recently, Pujade et al. showed that adding bevacizumab to chemotherapy significantly improves progression-free survival (PFS) in this subgroup of patients with poor prognoses (16.6 months versus 13.3 months in women treated with chemotherapy alone). Three case control studies have compared systemic chemotherapy and CRS (Cytoreduction Surgery) alone versus CRS plus HIPEC in patients with recurrent disease. They showed significantly improved results with the addition of HIPEC. In the French registry that included 474 patients with recurrence and peritoneal carcinomatosis, the median PFS was 13.8 months for platinum-resistant patients and 13 months for platinum-sensitive patients. Our hypothesis is that surgery would reduce the tumor burden and consequently the number of platinum-resistant tumor clones and that HIPEC would control the microscopic residual disease by increasing the tumor cell cytotoxicity.
We assume that adding a locoregional treatment to an "Aurelia-like" systemic treatment would improve the PFS. We aim to assess the benefit of adding surgery and HIPEC to the treatment of first or second platinum-resistant recurrence compared to chemotherapy + bevacizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cytoreductive surgery combined with HIPEC | Experimental | Procedure: Cytoreductive surgery combined with HIPECAll patients will start with three cycles of CT-BEV 15 mg/kg, and will then be randomly. Then one cycle of monochemotherapy without bevacizumab is administered and followed by an interval CRS and HIPEC with postoperative chemotherapy and bevacizumab (CT-BEV - 15 mg/kg once every 3 weeks) until disease progression |
| Aurelia arm | Active comparator | Drug: Chemotherapy and bevacizumab (CT-BEV)Chemotherapy and bevacizumab (CT-BEV) once every 3 weeks from enrollment until disease progression |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically confirmed platinum-resistant Epithelial Ovarian Carcinoma (EOC)(clinical recurrence or persistence within 6 months of last treatment);
- White blood cells >3,500/mm3, neutrophils ≥1,500/mm3, platelets ≥100,000/mm3;
- Good renal function: serum creatinine values <1.5 mg/dl, creatinine clearance >60 ml/min;
- Performance Status ≤2, Karnofsky Index ≥70%;
- Serum bilirubin ≤1.5 x Upper limit of normal (UNL) 2 mg/dl;
Key exclusion criteria (11 listed)
- Platinum-refractory EOC (i.e progression under platinum containing chemotherapy);
- Any prior malignancy not considered in complete remission for at least 2 years;
- Pregnancy or breastfeeding;
- Untreated central nervous system disease or symptomatic central nervous system metastasis, history or evidence of thrombotic or hemorrhagic disorders within 6 months before first study treatment;
- Uncontrolled hypertension or active clinically significant cardiovascular disease;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cytoreductive surgery combined with HIPECCytoreductive surgery combined with HIPEC (Cisplatin 70 mg/m2). | Procedure or surgery | Cytoreductive surgery combined with HIPEC |
| Chemotherapy and bevacizumab (CT-BEV)Chemotherapy and bevacizumab (CT-BEV) 15 mg/kg once every 3 weeks from enrollment until disease progression (RECIST 1.1) | Drug | Aurelia arm |
Primary outcome
Progression free survival
Time frame: Change from baseline to 36 months
Progression will be based on RECIST V1.1 criteria performed on thoraco-abdominopelvic tomodensitometry (TDM ) assessed every 3 months. There is a follow-up period of 36 months.
4 secondary outcomes
Overall survival
Time frame: From the randomization to the death or 36 months end of follow-up
Potential treatment-related mortality
Time frame: During the first 60 postoperative days
Potential treatment-related morbidity
Time frame: During the first 60 postoperative days
Quality of life assessment
Time frame: Baseline to 36 months end of follow-up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cytoreductive surgery combined with HIPEC and Chemotherapy and bevacizumab (CT-BEV) in people with Ovarian Epithelial Cancer, run by Hospices Civils de Lyon at 22 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Naoual BARKIN, MD,PhD (4 78 86 23 71 ext. +33, naoual.bakrin@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: Change from baseline to 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2019.