Evaluation of Symptom Benefit Rate of Trabectedin/PLD in Patients With Recurrent Ovarian Cancer

NCT03690739 | Terminated Phase 3 DMC

• 1 other identifier: AGO-OVAR 2.32
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 29

Brief Summary

This is an open-label, prospective, randomized, controlled, parallel group, multi-center phase III trial to evaluate the Symptom Benefit Rate of trabectedin/PLD in patients with recurrent ovarian cancer who achieve a stabilization of disease after 3 cycles of platinum-based reinduction therapy and with no clinical benefit.

Conditions

Recurrent Ovarian Carcinoma

Keywords

Symptom Benefit

Outcome Measures

Primary Outcomes (1)

• Symptom Benefit Rate

  Proportion of patients achieving a symptom benefit defined as an at least 10-point improvement according to EORTC QLQ-OV28; EORTC QLQ-OV28 is a questionnaire regarding Quality of Life specialized for Ovarian Cancer with points from 1 till 4 for each of the 28 questions (1=not at all, 2=a little, 3=quite a bit, 4=very much). Points will be summarized.

  from Baseline to 8 or 9 weeks after randomization, assessed at each visit

Secondary Outcomes (6)

• Time until definitive deterioration (TUDD )

  from Baseline until 24 months after randomization, assessed up to 54 months at each visit

• Progression-free survival (PFS)

  PFS is defined as time from randomization to disease progression according to RECIST v1.1, to death from any cause or to start of a new treatment (whichever occurs first), assessed up to 54 months

• Progression-free survival (PFS) rate at 6 months

  PFS is defined as time from randomization to disease progression according to RECIST v1.1, to death from any cause or to start of a new treatment (whichever occurs first) after six months

• Response Rate (RR)

  from randomization until patients achieving complete response (CR) or partial response (PR) as best overall response, assessed up to 54 months

• Global Health Status

  from baseline to end of treatment, assessed up to 54 months at each visit

Study Arms (2)

platinum-based chemotherapy

ACTIVE COMPARATOR

According to the investigator's discretion

Drug: Carboplatin; Drug: Gemcitabine; Drug: Bevacizumab; Drug: PLD; Drug: Paclitaxel; Drug: Cisplatin

PLD + Trabectedin

ACTIVE COMPARATOR

PLD 30 mg/m² + Trabectedin 1.1 mg/m² q21

Drug: PLD; Drug: Trabectedin

Interventions

Carboplatin DRUG

Administration according to investigator's discretion

platinum-based chemotherapy

Gemcitabine DRUG

Administration according to investigator's discretion

platinum-based chemotherapy

Bevacizumab DRUG

Administration according to investigator's discretion

platinum-based chemotherapy

PLD DRUG

Administration according to investigator's discretion

platinum-based chemotherapy

Paclitaxel DRUG

Administration according to investigator's discretion

platinum-based chemotherapy

Trabectedin DRUG

Administration 1.1 mg/m² q21

PLD + Trabectedin

Cisplatin DRUG

Administration according to investigator's discretion

platinum-based chemotherapy

Eligibility Criteria

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

You may qualify if:

• Females aged ≥ 18 years at time of signing informed consent form.
• Histologically proven diagnosis of cancer of the ovary, the fallopian tube or primary peritoneal cancer.
• Measurable or non-measurable disease (according RECIST v1.1) or CA-125 assessable disease (according GCIG criteria) or histologically proven diagnosis of relapse.
• Platinum-treatment free interval (TFIp) \> 6 months prior to cycle 1 day 1 of reinduction therapy.
• Disease stabilization without remission or progression ac-cording to RECIST or GCIG criteria after three cycles of platinum-based chemotherapy for recurrent disease.
• Symptomatic disease at time of baseline abdominal/GI symptom scale score \>15 (EORTC QLQ-OV28)
• Completion of EORTC QLQ-OV28 at Baseline within 7 days prior to treatment start.
• Patients should have received previously a taxane derivative.
• ECOG performance status ≤ 2.
• Life expectancy of at least 12 weeks.
• Adequate bone marrow, renal and hepatic function defined as:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Platelet count ≥ 100 x 10\^9/L
• Hemoglobin ≥ 9.0 g/dL
• Serum creatinine ≤1.5 mg/dL (≤ 132.6 µmol/L) or creatinine clearance ≥ 60 mL/min

You may not qualify if:

• Ovarian tumors of low malignant potential (e.g. borderline tumors).
• Non-epithelial ovarian or mixed epithelial/non epithelial tumors (e.g. mixed Müllerian tumors).
• Patients with an objective response in terms of a partial or complete remission or alternatively progressive disease ac-cording to RECIST or GCIG criteria after three cycles of platinum-based reinduction chemotherapy.
• Patients who have received previous radiotherapy for ovarian cancer.
• History of congestive heart failure (NYHA classification \> 2, even if medically con-trolled).
• History of myocardial infarction within the last six months (documented or by electrocardiogram).
• History of atrial or ventricular arrhythmias.
• Impaired liver function, hyperbilirubinemia, Serum creatinine \>1.5 mg/dL or \> 132.6 μmol/L or creatinine clearance \< 60 mL/min, left ventricular ejection fraction \< 45 %.
• Severe active or uncontrolled infection.
• Concurrent severe medical problems unrelated to malignancy, which would significantly limit full compliance with the trial or expose the patient to extreme risk or decreased life expectancy.
• Patients with known hypersensitivity to the active substance or their compounds related to trabectedin or PLD and patients with known hypersensitivity to one of active substances or one of their compounds used in platinum-based chemotherapy as described in the Summaries of Medicinal Products.
• Patients with potential risks according to contraindication, warnings or interactions of the used chemotherapeutic agents as stated in the SmPCs are not eligible for participation in this trial.
• Patients with contraindication regarding CT or MRI (only in case of contrast allergy) are excluded.
• Women of childbearing potential (WOCBP) not using highly effective contraceptive methods.
• Pregnancy or breast-feeding.

Sponsors & Collaborators

• AGO Research GmbH: lead

Study Sites (29)

Klinikum Aschaffenburg-Alzenau

Aschaffenburg, Bavaria, 63739, Germany

Location

Hochtaunus-Kliniken

Bad Homburg, Germany

Location

Sozialstiftung Bamberg

Bamberg, Germany

Location

Evangelisches Krankenhaus Bergisch Gladbach

Bergisch Gladbach, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

Universitätsfrauenklinik Bonn

Bonn, Germany

Location

Schwerpunktpraxis für Onkologie / Hämatologie

Bottrop, Germany

Location

Frauenärzte Casparistraße

Braunschweig, Germany

Location

Universitätsklinikum Carl Gustav Carus

Dresden, Germany

Location

Evang. Kliniken Essen-Mitte

Essen, Germany

Location

Agaplesion Markus Krankenhaus

Frankfurt, Germany

Location

Universitätsmedizin Greifswald

Greifswald, Germany

Location

Mammazentrum Hamburg am Krankenhaus Jerusalem

Hamburg, Germany

Location

Klinikum Itzehoe

Itzehoe, Germany

Location

ViDia Christliche Kliniken Karlsruhe

Karlsruhe, Germany

Location

Klinikum Ludwigsburg

Ludwigsburg, Germany

Location

Klinikum Magdeburg

Magdeburg, Germany

Location

Katholisches Klinikum Mainz

Mainz, Germany

Location

Universitätsfrauenklinik Mannheim

Mannheim, Germany

Location

Klinikum Memmingen

Memmingen, Germany

Location

Klinikum rechts der Isar

München, Germany

Location

Kliniken des Landkreises Neumarkt

Neumarkt, Germany

Location

Universitätsklinik für Innere Medizin, Onkologie und Hämatologie

Oldenburg, Germany

Location

Klinikum Ernst von Bergmann

Potsdam, Germany

Location

Agaplesion Diakonieklinikum Rotenburg

Rotenburg (Wümme), Germany

Location

Thüringen Kliniken "Georgius Agricola"

Saalfeld, Germany

Location

g.Sund Gyn. Kompetenzzentrum

Stralsund, Germany

Location

Kreiskrankenhaus "Johann Kentmann"

Torgau, Germany

Location

Helios Dr. Horst Schmidt Kliniken

Wiesbaden, Germany

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Carboplatin; Gemcitabine; Bevacizumab; 1-dodecylpyridoxal; Paclitaxel; Trabectedin; Cisplatin

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

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Dioxoles; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Felix Hilpert, MD, PhD

  Mammazentrum am Krankenhaus Jerusalem, Hamburg

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2018
• First Posted: October 1, 2018
• Study Start: August 9, 2019
• Primary Completion: March 3, 2021
• Study Completion: March 3, 2021
• Last Updated: February 24, 2022

Record last verified: 2022-02

Locations

DE (29)