European Trial on Enhanced DNA Repair Inhibition in Ovarian Cancer

NCT03783949 | Completed Phase 2 Results DMC

• 1 other identifier: 2017-004058-40
• Study Type: interventional
• Target: 122
• Locations: 5 countries
• Sites: 13

Brief 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). 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.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma

Keywords

Ganetespib; Niraparib

Outcome Measures

Primary Outcomes (1)

• 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

  3 years 10 months

Secondary Outcomes (11)

• Progression-free Survival in BRCA Mutated Patients

  3 years 10 months

• Post-progression PFS (PFS2)

  3 years 10 months

• Time to First Subsequent Therapy (TFST)

  3 years 10 months

• Time to Second Subsequent Therapy (TSST)

  3 years 10 months

• Progression-free Survival in Patients Without BRCA Mutation or With Unknown BRCA Status

  3 years 10 months

Study Arms (3)

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)

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)

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)

Drug: Ganetespib; Drug: Niraparib; Drug: Carboplatin

Interventions

Ganetespib DRUG

Ganetespib dose during chemotherapy will be 150mg/m² (q3w) Ganetespib dose during maintenance treatment will be 100mg/m² (q1w)

First experimental arm (arm B); Second experimental arm (arm C)

Niraparib DRUG

Niraparib starting dose during maintenance treatment will be 200mg or 300mg depending on subject's body weight and subject neutrophil count (QD)

First experimental arm (arm B); Second experimental arm (arm C); Standard arm (arm A)

Carboplatin DRUG

In combination with Gemcitabine: Carboplatin dose will be AUC4 (q3w) In combination with Paclitaxel: Carboplatin dose will be AUC5 (q3w)

First experimental arm (arm B); Second experimental arm (arm C); Standard arm (arm A)

Paclitaxel DRUG

Paclitaxel dose will be 175mg/m² (q3w)

Standard arm (arm A)

Gemcitabine DRUG

Gemcitabine dose will be 1000mg/m² (q3w, d1 \& d8)

Standard arm (arm A)

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• European Commission: collaborator

Study Sites (13)

Medical University of Innsbruck

Innsbruck, 6020, Austria

Location

UZLeuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Centre de lutte contre le cancer Francois Baclesse

Caen, 14076, France

Location

Centre anticancereux Leon Berard

Lyon, 69008, France

Location

Assistance Publique Hôpitaux de Paris

Paris, 75004, France

Location

Universitätsmedizin Berlin Charité

Berlin, 10117, Germany

Location

Universitätsklinikum Bonn

Bonn, 53127, Germany

Location

Universitätsklinikum Dresden

Dresden, 01069, Germany

Location

Kliniken Essen Mitte, Evang. Huyssens- Stiftung/Knappschaft GmbH

Essen, 45136, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Azienda Ospedaliero Bologna

Bologna, 40138, Italy

Location

Fondazione IRCCS Istituto Nazionale dei tumori Milano

Milan, 20133, Italy

Location

Università Cattolica del Sacro Cuore

Rome, 00168, Italy

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

STA 9090; niraparib; Carboplatin; Paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Ellen Reynders, SC
• Organization: UZLeuven

ellen.reynders@uzleuven.be

+3216342996

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: December 14, 2018
• First Posted: December 21, 2018
• Study Start: November 30, 2018
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: June 11, 2025
• Results First Posted: June 11, 2025

Record last verified: 2025-06

Locations

AU (1); BE (1); FR (3); DE (5); IT (3)