Phase III randomized clinical trial evaluating hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer considering two different settings: Primary Debulking Surgery (PDS) and Interval Debulking Surgery (IDS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Oscar Lambret

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 May 2019 → ongoing

Decision date (initial)

2024-11-18

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Centre Oscar Lambret

External identifiers

EU CT number

2024-514706-31-01

EudraCT number

2018-003680-62

ClinicalTrials.gov

NCT03842982

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of this trial is to assess the efficacy, in terms of disease-free survival (DFS), the use of HIPEC treatment combined with standard care (PDS or IDS) or standard care alone (PDS or IDS alone).

Secondary objectives 7

1. To evaluate efficacy of HIPEC in terms of overall survival (OS) in combination with standard of care
2. To evaluate the impact of HIPEC on the safety
3. To evaluate the impact of HIPEC on the feasibility of adjuvant treatment if an adjuvant treatment is planned after surgery
4. To evaluate the trade-off between efficacy and morbidity using the Q-TWiST approach
5. To evaluate the impact of HIPEC in terms of quality of life
6. Exploratory Objective : To evaluate the impact of HIPEC on the count of residual viable cells (evaluated by flow cytometry) in abdominal drainage fluids (for patients recruited in Centre Oscar Lambret only)
7. Exploratory Objective : To constitute a biobank (tumor samples and blood samples) for future translational research projects

Conditions and MedDRA coding

Epithelial ovarian cancer, Fallopian tube ovarian cancer, Peritoneal ovarian cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Age ≥18 years and ≤ 76 years
2. Histologically proven primary epithelial ovarian carcinoma or fallopian tube carcinoma or peritoneal carcinoma (serous papillary adenocarcinoma, clear-cell carcinoma, mucinous adenocarcinoma and endometrioid carcinoma). In case of Primary Debulking Surgery (PDS), the patient can be included based on an extemporaneous diagnosis of stage III invasive carcinoma.
3. Pre-therapeutic FIGO stage III
4. Patient eligible for a. Primary Debulking Surgery (PDS) with planned adjuvant chemotherapy +/- bevacizumab or other targeted therapy b. Or Interval Debulking Surgery (IDS) after neo-adjuvant chemotherapy +/- bevacizumab or other targeted therapy, with or without planned adjuvant chemotherapy +/- bevacizumab or other targeted therapy. In case of neo-adjuvant chemotherapy, surgery should be performed in a time interval of 3 to 5 weeks in case of chemotherapy without bevacizumab, and in a time interval of 4 to 6 weeks if chemotherapy is combined with bevacizumab. The patient remains eligible for the trial if surgery is delayed beyond the recommended time interval.
5. WHO Performance Status ≤ 2
6. Physical status score ASA2 ≤ 2 or ASA = 3 if only related to a BMI ≥ 40 or to malignant ascites
7. Adequate bone marrow and renal function, as evidenced by the following tests performed within 7 days prior to surgery: - Absolute Neutrophil Count (ANC) ≥1,500/mm3 - Platelets ≥100,000/mm3 - Aspartate aminotransferase (ALT)/ Alanine aminotransferase (ALT) ≤2.5 × upper normal limit (UNL) (≤5.0 × ULN in case of liver metastases) - Total bilirubin ≤1.5 × ULN (except in case of Gilbert’s disease) - Creatinine clearance ≥ 60 mL/ min/ 1.73m2 (estimated according to MDRD formula)
8. Negative serum pregnancy test within 7 days prior to surgery for women of childbearing potential. For non-menopaused women, if no hysterectomy is planned, willing to accept the use of an effective contraceptive regimen3 during the treatment period and at least 6 months after the end of treatment (surgery or adjuvant chemotherapy)
9. Absence of contraindication to receive the products used in this study (cisplatin and products used in neo-adjuvant/ adjuvant chemotherapy) according to the most recent SmPC of these products (available at http://base-donnees-publique.medicaments.gouv.fr/)
10. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up
11. Signed, IRB-approved written informed consent
12. Patient covered by the French or Belgian “Social Security” regime
13. Criteria to be checked per-operatively for confirmation of enrolment and randomization : Residual disease after surgery CC-0 (no macroscopic residue) or CC-1 (residue < 2.5 mm)
14. Criteria to be checked per-operatively for confirmation of enrolment and randomization : Per-operative hemorrhage < 2.5 L
15. Criteria to be checked per-operatively for confirmation of enrolment and randomization : Strictly less than 3 digestive resections (other than appendectomy) performed during surgery
16. Criteria to be checked per-operatively for confirmation of enrolment and randomization : Diuresis maintained during surgery, without oliguria or anuria (per-operatory diuresis ≥ 0,5 mL/ kg/ h)

Exclusion criteria 13

1. Benign disease, borderline disease, non epithelial ovarian carcinoma or carcinosarcoma
2. Cirrhosis
3. Known hypersensitivity to any of the trial drugs, trial drug classes, or excipients in the formulation
4. Auditory impairment (i.e. if hearing aid is fitted or if the patient is complaining. In cases of doubt, an audiogram should be performed.)
5. Dehydration or intercurrent disease that contraindicates hyperhydration (including cardio-respiratory disease)
6. Other uncontrolled intercurrent disease including, but not limited to: diabetes; hypertension; symptomatic congestive heart or pulmonary failure; renal, hepatic or severe gastrointestinal (associated with diarrhea) chronic disease
7. Any unresolved NCI-CTCAE Grade ≥ 2 toxicity from previous anticancer therapy (excluding alopecia), or NCI-CTCAE Grade ≥ 3 for anemia
8. Concomitant treatment with prophylactic phenytoin
9. Receipt of live attenuated vaccine, including yellow fever vaccine, within 30 days prior to inclusion (and, if patient is enrolled, up to 30 days after the last administration of study treatment)
10. Pregnant or breastfeeding woman
11. Psychiatric illness or social situation that would limit compliance with study requirement, substantially increase the risk of side effects, or compromise the ability of the patient to give written informed consent
12. Inability to comply with medical follow-up of the trial (geographical, social or psychic reasons)
13. Person under guardianship or curatorship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease-Free Survival (DFS) will be computed as the time interval between randomization and progression, relapse or death from any cause. Progression and relapses will be assessed according to GCIG criteria1 and ideally confirmed by local tumor board. For patients alive without progression or relapse, data will be censored at the date of last follow-up visit.

Secondary endpoints 7

1. Overall survival : OS will be computed as the time interval between randomization and death from any cause. For patients alive, data will be censored at the date of last follow-up.
2. Adverse events will be evaluated according to NCI-CTCAE V5.0 over the whole treatment duration from randomization up to the end of treatment (surgery or chemotherapy) plus 30 days, excluding AE unequivocally related to the disease under study or its progression. Adverse events of grade 3 or more (grade 3+) will be counted as severe adverse events.
3. The impact of HIPEC on the feasibility of adjuvant treatment will be assessed by describing the time interval between surgery and start of adjuvant chemotherapy. We will consider that start of chemotherapy is delayed if this time interval is larger than 6 weeks. In this case, the reasons will be described. - describing the total number of chemotherapy courses (neo-adjuvant+adjuvant). If the total number of chemotherapy course is below the planned number of 6, the reasons will be described.
4. Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) computed from survival times (overall survival and progression-free survival) and adverse events data (date of occurrence of grade 3+ adverse event) as detailed in the statistical considerations.
5. Quality of life will be evaluated using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire–Score 30 (QLQ-C30), and Quality of Life Questionnaire–Ovarian Cancer Module (QLQ-OV28)
6. Exploratory endpoint : Count of residual viable cells (evaluated by flow cytometry) in abdominal drainage fluids
7. Exploratory endpoint : Further research projects on the constituted biobank (tumor samples and blood samples) could be performed if additional and specific funding is obtained

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Oscar Lambret

Sponsor organisation

Centre Oscar Lambret

Address

3 Rue Frederic Combemale

City

Lille

Postcode

59000

Country

France

Scientific contact point

Organisation

Centre Oscar Lambret

Contact name

Clinical Research Sponsor Unit

Public contact point

Organisation

Centre Oscar Lambret

Contact name

Clinical Research Sponsor Unit

Locations

2 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications