Ovarian CancerPhase 2EUDARIONCT03783949
European Trial on Enhanced DNA Repair Inhibition in Ovarian Cancer
A Phase 2 study testing Ganetespib, Niraparib and Carboplatin in people with Ovarian Cancer and Fallopian Tube Cancer, run by Universitaire Ziekenhuizen KU Leuven at 13 sites in 5 countries.
Trial summary
This study will be performed in women with platinum-sensitive, high-grade serous, high-grade endometrioid, undifferentiated epithelial ovarian cancer, carcinosarcoma, fallopian tube or primary peritoneal cancer (proven by central histo-pathological review). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma
- What is being tested?
- Ganetespib, Niraparib and Carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 122 participants
- Where
- 13 sitesin 5 countries
- Study dates
- 30 Nov 2018to 1 Sep 2023
- Phase
- Phase 2
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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must meet the following criteria to be eligible for study entry:
- Ability to understand and willingness to sign and date a written informed consent document
- Female patients ≥18 years of age
- High-grade serous, high-grade endometrioid, undifferentiated epithelial ovarian cancer, carcinosarcoma, fallopian tube or primary peritoneal cancer
- Platinum-sensitive relapse >6months after previous platinum-based treatment (calculated from the first day of the last cycle of the last platinum-based chemotherapy until the date of progression confirmed according to RECIST 1.1 on imaging)
- No limits in number of prior lines
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- Measurable or evaluable disease according to RECIST 1.1
- ECOG performance status 0-1
- Adequate functions of the bone marrow
- Platelets ≥ 100 x 109/L
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Adequate function of the organs
- Creatinine < 2 mg/dl (<177 μmol/L)
- Total bilirubin ≤ 1.5 x upper limit of normal (≤ 2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN
- SGOT/SGPT (AST/ALT) ≤ 2.5 x upper limit of normal unless liver metastases are present, in which case they must be ≤ 5 x ULN
- Urinanalysis or urine dipstick for proteinuria less than 2+. Patients with ≥ 2+ on dipstick should undergo 24-hour urine collection and must demonstrate < 1 g of protein/24 hours; except the proteinuria is clearly related to a catheter in the urinary system.
- Adequate coagulation parameter: aPTT ≤ 1.5 x ULN (patients on heparin treatment must have an aPTT between 1.5-2.5 x ULN), or INR ≤ 1.5. (In patients receiving anticoagulants (such as warfarin) INR must be between 2.0 and 3.0 in two consecutive measurements 1-4 days apart).
- Participant receiving corticosteroids (dose < 10 mg/day methylprednisolone equivalent), including inhaled steroids, may continue as long as their dose is stable for at least 4 weeks prior to initiating protocol therapy.
- Participants must agree to not donate blood during the study or for 90 days after the last dose of study treatment
- Female participant has a negative serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of non-childbearing potential. Non-childbearing potential is defined as follows (by other than medical reasons):
- ≥ 45 years of age and has not had menses for >1 year
- Patients who have been amenorrhoeic for < 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
- Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by imaging. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. See below for a list of acceptable birth control methods. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
- Birth Control: Participants of childbearing potential who are sexually active and their partners must agree to the use of a highly effective form of contraception throughout their participation beginning with time of consent, during the study treatment and for 180 days after last dose of study treatment(s):
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- Oral route
- Intravaginal route
- Transdermal route
- Progestogen-only hormonal contraception associated with inhibition of ovulation
- Oral
- Injectable
- Implantable
- Intrauterine device
- Intrauterine hormone-releasing system
- Bilateral tubal occlusion
- Vasectomized partner
- Sexual abstinence, if the preferred and usual lifestyle of the subject
- Participant must agree to not breastfeed (or store breast milk for use) during the study or for 180 days afer the last dose of study treatment.
- Haemoglobin ≥8.5 g/dl (patients may not receive a transfusion within 4 weeks prior to initiating study treatment)
- Able to take oral medications
- Availability of archival ovarian cancer tissue from primary diagnosis (delivery of FFPE block or slides is prerequisite for randomisation)
Who cannot join
- Patients who meet any of the following criteria will be excluded from study entry:
- Ovarian tumours with low malignant potential (i.e. borderline tumours)
- Any prior radiotherapy to the pelvis or abdomen, or any radiotherapy encompassing > 20 % of the bone marrow within 2 weeks, or any radiotherapy within 1 week prior to Day 1 of protocol therapy
- Surgery (including open biopsy and traumatic injury) within 4 weeks prior to first dose of Ganetespib, or anticipation of the need for major surgery during study treatment
- Minor surgical procedures, within 24 hours prior to the first study treatment
- Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
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- Any serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, chronic obstructive pulmonary disease, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
- Current or recent (within 10 days prior to the first study drug dose) chronic daily treatment with aspirin (>325 mg/day).
- Patients with a history of diagnosis, detection or treatment of any prior malignancies ≤ 2 years prior to initiating protocol therapy, except: basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated.
- Clinically significant gastro-intestinal (GI) tract abnormalities that may increase the risk for GI bleeding and / or perforation including but not limited to: active peptic ulcer disease, known intraluminal metastatic lesion/s with risk of bleeding; inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), history of bowel obstruction within 1 year prior to first study treatment (excluding postoperative, i.e. within 4 weeks post surgery), other GI condition with increased risk of perforation such as recurrence deeply infiltrating into the muscularis or mucosa of the rectosigmoid or the mucosa of the bladder, or history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
- Non-healing wound or non-healing bone fracture
- Patients with symptomatic brain or leptomeningeal metastases (patients who are asymptomatic since treatment of brain or leptomeningeal metastases, eg. after irradiation, are eligible)
- Left ventricular ejection fraction (LVEF) defined by ECHO below the institutional lower limit of normal
- Cerebrovascular accident (CVA)/ stroke or transient ischemic attack (TIA) or sub-arachnoid haemorrhage within ≤ 6 months prior to first study treatment.
- Significant cardiac disease: New York Heart Association (NYHA) Class 3 or 4; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty or coronary atrial or ventricular cardiac arrhythmias
- History of prolonged QT syndrome, or family member with prolonged QT syndrome
- QTc interval > 470 msec when 3 consecutive ECG values are averaged
- Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a Class Ia antiarrhythmic drug (e.g. sotalol, amiodarone, dofetilide). Use of other antiarrhythmic drugs is permitted
- Second- or third-degree atrioventricular (AV) block, except: treated with a permanent pacemaker Complete left bundle branch block (LBBB)
- History of evidence of haemorrhagic disorders, patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorders, coagulopathy or tumour involving major vessels.
- Participation in another clinical study with experimental therapy within 28 days before start of treatment.
- Participant must not be simultaneously enrolled in any interventional clinical trial.
- Women who are pregnant or are lactating
- Patients unable to be regularly followed for any reason (geographic, familiar, social, psychologic, housed in an institution eg. prison because of a court agreement or administrative order)
- Subjects that are dependent on the sponsor/CRO or investigational site as well as on the investigator.
- History of known hypersensibility against any medication used in the study
- Intolerance / Hypersensitivity reactions to components and excipients of study drugs
- Peripheral neuropathy of grade >2 per NCI CTCAE, version 4.03, within 4 weeks prior to randomisation
- Any other condition that, in the opinion of the investigator, may compromise the safety, compliance of the patient, or would preclude the patient from successful completion of the study
Trial locations and contacts
13 sites in 5 countries.
13 sites in 5 countries
Germany5 sites
Universitätsmedizin Berlin Charité
Berlin, 10117
Universitätsklinikum Bonn
Bonn, 53127
Universitätsklinikum Dresden
Dresden, 01069
Kliniken Essen Mitte, Evang. Huyssens- Stiftung/Knappschaft GmbH
Essen, 45136
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246
France3 sites
Centre de lutte contre le cancer Francois Baclesse
Caen, 14076
Centre anticancereux Leon Berard
Lyon, 69008
Assistance Publique Hôpitaux de Paris
Paris, 75004
Italy3 sites
Azienda Ospedaliero Bologna
Bologna, 40138
Fondazione IRCCS Istituto Nazionale dei tumori Milano
Milan, 20133
Università Cattolica del Sacro Cuore
Rome, 00168
About this study
Official title: A Multicentre, Open-label, Three-arm Randomised Phase II Trial Assessing the Safety and Efficacy of the HSP90 Inhibitor Ganetespib in Combination With Carboplatin Followed by Maintenance Treatment With Niraparib Versus Ganetespib Plus Carboplatin Followed by Ganetespib and Niraparib Versus Carboplatin in Combination With Standard Chemotherapy Followed by Niraparib Maintenance Treatment in Platinum-sensitive Ovarian Cancer Patients
This study will be performed in women with platinum-sensitive, high-grade serous, high-grade endometrioid, undifferentiated epithelial ovarian cancer, carcinosarcoma, fallopian tube or primary peritoneal cancer (proven by central histo-pathological review).
A total of 120 subjects will be randomized (1:1:1) to three different treatment arms: (A) Standard arm (arm A): Carboplatin (AUC5 d1, q3w i.v.) in combination with Paclitaxel (175 mg/m² d1, q3w i.v.) or Carboplatin (AUC4 d1, q3w i.v.) in combination with Gemcitabine (1000 mg/m² d1, d8, q3w i.v.) followed by maintenance therapy with Niraparib (200/ 300 mg oral daily, q4w) // (B) First experimental arm (arm B): Ganetespib (150 mg/m2, d1, q3w) in combination with Carboplatin (AUC5 d1, q3w i.v.) followed by maintenance treatment with Niraparib (200/ 300 mg oral daily, q4w) // (C) Second experimental arm (arm C): Ganetespib (150 mg/m² d1, q3w i.v.) plus Carboplatin (AUC5 d1, q3w i.v.) followed by Ganetespib (100 mg/m² d1, d8, d15, d22, q4w i.v.) and Niraparib (200 mg oral daily, q4w).
Chemotherapy treatment will be given for 6 cycles, maintenance treatment with Ganetespib will be given for a maximum of 9 months or until disease progression, maintenance treatment with Niraparib can continue until disease progression.
- Being tested
- Ganetespib, Niraparib, Carboplatin, Paclitaxel, Gemcitabine
- Keywords
- Ganetespib, Niraparib
- Medical subject headings
- Ovarian Neoplasms, Fallopian Tube Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GanetespibDrug
Ganetespib dose during chemotherapy will be 150mg/m² (q3w) Ganetespib dose during maintenance treatment will be 100mg/m² (q1w)
NiraparibDrug
Niraparib starting dose during maintenance treatment will be 200mg or 300mg depending on subject's body weight and subject neutrophil count (QD)
CarboplatinDrug
In combination with Gemcitabine: Carboplatin dose will be AUC4 (q3w) In combination with Paclitaxel: Carboplatin dose will be AUC5 (q3w)
PaclitaxelDrug
Paclitaxel dose will be 175mg/m² (q3w)
GemcitabineDrug
Gemcitabine dose will be 1000mg/m² (q3w, d1 \& d8)
| Study group | Role | What they receive |
|---|---|---|
| Standard arm (arm A) | Active comparator | Carboplatin (AUC5 d1, q3w i.v.) in combination with Paclitaxel (175 mg/m² d1, q3w i.v.) or Carboplatin (AUC4 d1, q3w i.v.) in combination with Gemcitabine (1000 mg/m² d1, d8, q3w i.v.) followed by maintenance therapy with Niraparib (200/ 300 mg oral daily, q4w) Receives: Drug: Niraparib; Drug: Carboplatin; Drug: Paclitaxel; Drug: Gemcitabine |
| First experimental arm (arm B) | Experimental | Ganetespib (150 mg/m2, d1, q3w) in combination with Carboplatin (AUC5 d1, q3w i.v.) followed by maintenance treatment with Niraparib (200/ 300 mg oral daily, q4w) Receives: Drug: Ganetespib; Drug: Niraparib; Drug: Carboplatin |
| Second experimental arm (arm C) | Experimental | Ganetespib (150 mg/m² d1, q3w i.v.) plus Carboplatin (AUC5 d1, q3w i.v.) followed by Ganetespib (100 mg/m² d1, d8, d15, d22, q4w i.v.) and Niraparib (200 mg oral daily, q4w) Receives: Drug: Ganetespib; Drug: Niraparib; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Measured: 3 years 10 months
Secondary outcomes (11)
Progression-free Survival in BRCA Mutated Patients
Progression-free survival analysis in BRCA mutated patients
Measured: 3 years 10 months
Post-progression PFS (PFS2)
Post-progression PFS (PFS2) analysis
Measured: 3 years 10 months
Time to First Subsequent Therapy (TFST)
Time to First Subsequent Therapy (TFST) analysis
Measured: 3 years 10 months
Time to Second Subsequent Therapy (TSST)
Time to Second Subsequent Therapy (TSST) analysis
Measured: 3 years 10 months
Progression-free Survival in Patients Without BRCA Mutation or With Unknown BRCA Status
Progression-free Survival analysis in Patients without BRCA mutation or with unknown BRCA status
Measured: 3 years 10 months
Objective Response Rate (ORR)
Objective response rate (ORR) analysis
Measured: 3 years 10 months
Overall Survival (OS)
Overall survival (OS) analysis
Measured: 3 years 10 months
Progression-free Survival in Patients With Prior PARPi Treatment
Progression-free Survival analysis in Patients with prior PARPi treatment
Measured: 3 years 10 months
Progression-free Survival in Patients With One Prior Line of Therapy
Progression-free Survival analysis in Patients with one prior line of therapy
Measured: 3 years 10 months
Progression-free Survival in Patients With More Then One Prior Line of Therapy
Progression-free Survival analysis in Patients with more then one prior line of therapy
Measured: 3 years 10 months
Progression-free Survival in Patients Without Prior PARPi Treatment
Progression-free Survival analysis in Patients without prior PARPi treatment
Measured: 3 years 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2018
- Study start30 Nov 2018
- Primary completion1 Sep 2023
- Study completion1 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Standard arm (arm A): Carboplatin (AUC5 d1, q3w i.v.) in combination with Paclitaxel (175 mg/m² d1, q3w i.v.) or Carboplatin (AUC4 d1, q3w i.v.) in combination with Gemcitabine (1000 mg/m² d1, d8, q3w i.v.) followed by maintenance therapy with Niraparib (200/ 300 mg oral daily, q4w) First experimental arm (arm B): Ganetespib (150 mg/m2, d1, q3w) in combination with Carboplatin (AUC5 d1, q3w i.v.) followed by maintenance treatment with Niraparib (200/ 300 mg oral daily, q4w) Second experimental arm (arm C): Ganetespib (150 mg/m² d1, q3w i.v.) plus Carboplatin (AUC5 d1, q3w i.v.) followed by Ganetespib (100 mg/m² d1, d8, d15, d22, q4w i.v.) and Niraparib (200 mg oral daily, q4w)
- Masking
- None (open label)
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- European Commission
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03783949
- Sponsor's protocol ID
- 2017-004058-40
- Other IDs
- 2017
- Acronym
- EUDARIO
- Status last verified
- Jun 2025
- First submitted
- 14 Dec 2018
- Last updated
- 11 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No