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

Recurrent Ovarian Carcinoma Clinical Trial

Official title:

Trabectedin/PLD Versus Continuation of Platinum-based Chemo-therapy in Patients With Disease Stabilization and no Symptom Benefit Under Platinum-based Chemotherapy for Recurrent Ovarian Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03690739
• Other study ID #: AGO-OVAR 2.32
• Status: Terminated
• Phase: Phase 3
• Start date: August 9, 2019
• Est. completion date: March 3, 2021

Study information

• Verified date: February 2022
• Source: AGO Research GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Approximately 330 patients will be randomized in a 1:1 ration to the treatments specified below: Arm A - Platinum-based chemotherapy according to investigator's discretion Arm B - Pegylated liposomal doxorubicin 30 mg/m² + Trabectedin 1.1 mg/m² (q3w)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: March 3, 2021
• Est. primary completion date: March 3, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Females aged = 18 years at time of signing informed consent form.

2. Histologically proven diagnosis of cancer of the ovary, the fallopian tube or primary peritoneal cancer.

3. Measurable or non-measurable disease (according RECIST v1.1) or CA-125 assessable disease (according GCIG criteria) or histologically proven diagnosis of relapse.

4. Platinum-treatment free interval (TFIp) > 6 months prior to cycle 1 day 1 of reinduction therapy.

5. Disease stabilization without remission or progression ac-cording to RECIST or GCIG criteria after three cycles of platinum-based chemotherapy for recurrent disease.

6. Symptomatic disease at time of baseline abdominal/GI symptom scale score >15 (EORTC QLQ-OV28)

7. Completion of EORTC QLQ-OV28 at Baseline within 7 days prior to treatment start.

8. Patients should have received previously a taxane derivative.

9. ECOG performance status = 2.

10. Life expectancy of at least 12 weeks.

11. 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
• Creatine phosphokinase (CPK) = 2.5 x ULN
• Serum aspartate aminotransferase (AST, SGOT) or alanine aminotransferase (ALT, SGPT) = 2.5 x ULN (= 5 x ULN in the presence of liver metastases)
• Alkaline phosphatase (ALP) = 2.5 ULN
• Serum bilirubin = ULN
• Albumin = 25 g/l

12. Participation in an informed consent discussion with the appropriate trial-related health care representative, full understanding of the implications and constraints of the protocol, and provision of written informed consent prior to the commencement of the trial-related procedures.

13. Geographically accessibility for treatment and follow-up.

14. For women of childbearing potential (WOCBP): agreement to remain abstinent (refrain from heterosexual inter-course) or use a contraceptive method with a failure rate of < 1 per-centage per year during the treatment period and for at least six months after administration of the last dose of chemo-therapy. A woman is considered to be of childbearing po-tential if she is postmenarcheal, has not reached a post-menopausal state (= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries, fal-lopian tubes, and/or uterus). Examples of contraceptive methods with a failure rate of < 1 percentage per year in-clude but are not limited to bilateral tubal ligation and/or oc-clusion, male sterilization, and intrauterine devices, and nor-mal and low dose combined oral pill plus male condom or Cerazette (desogestrel) plus male condom. Cerazette is currently the only highly efficacious progesterone based pill. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation meth-ods) and withdrawal are not acceptable methods of contra-ception.

Exclusion Criteria:

1. Ovarian tumors of low malignant potential (e.g. borderline tumors).

2. Non-epithelial ovarian or mixed epithelial/non epithelial tumors (e.g. mixed Müllerian tumors).

3. 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.

4. Patients who have received previous radiotherapy for ovarian cancer.

5. History of congestive heart failure (NYHA classification > 2, even if medically con-trolled).

6. History of myocardial infarction within the last six months (documented or by electrocardiogram).

7. History of atrial or ventricular arrhythmias.

8. 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 %.

9. Severe active or uncontrolled infection.

10. 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.

11. 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.

12. 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.

13. Patients with contraindication regarding CT or MRI (only in case of contrast allergy) are excluded.

14. Women of childbearing potential (WOCBP) not using highly effective contraceptive methods.

15. Pregnancy or breast-feeding.

Related Conditions & MeSH terms

• Recurrent Ovarian Carcinoma

Intervention

Drug:
• Carboplatin
Administration according to investigator's discretion
• Gemcitabine
Administration according to investigator's discretion
• Bevacizumab
Administration according to investigator's discretion
• PLD
Administration according to investigator's discretion
• Paclitaxel
Administration according to investigator's discretion
• PLD
Administration 30 mg/m² q21
• Trabectedin
Administration 1.1 mg/m² q21
• Cisplatin
Administration according to investigator's discretion

Locations

Country	Name	City	State
Germany	Klinikum Aschaffenburg-Alzenau	Aschaffenburg	Bayern
Germany	Hochtaunus-Kliniken	Bad Homburg
Germany	Sozialstiftung Bamberg	Bamberg
Germany	Evangelisches Krankenhaus Bergisch Gladbach	Bergisch Gladbach
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsfrauenklinik Bonn	Bonn
Germany	Schwerpunktpraxis für Onkologie / Hämatologie	Bottrop
Germany	Frauenärzte Casparistraße	Braunschweig
Germany	Universitätsklinikum Carl Gustav Carus	Dresden
Germany	Evang. Kliniken Essen-Mitte	Essen
Germany	Agaplesion Markus Krankenhaus	Frankfurt
Germany	Universitätsmedizin Greifswald	Greifswald
Germany	Mammazentrum Hamburg am Krankenhaus Jerusalem	Hamburg
Germany	Klinikum Itzehoe	Itzehoe
Germany	ViDia Christliche Kliniken Karlsruhe	Karlsruhe
Germany	Klinikum Ludwigsburg	Ludwigsburg
Germany	Klinikum Magdeburg	Magdeburg
Germany	Katholisches Klinikum Mainz	Mainz
Germany	Universitätsfrauenklinik Mannheim	Mannheim
Germany	Klinikum Memmingen	Memmingen
Germany	Klinikum rechts der Isar	München
Germany	Kliniken des Landkreises Neumarkt	Neumarkt
Germany	Universitätsklinik für Innere Medizin, Onkologie und Hämatologie	Oldenburg
Germany	Klinikum Ernst von Bergmann	Potsdam
Germany	Agaplesion Diakonieklinikum Rotenburg	Rotenburg
Germany	Thüringen Kliniken "Georgius Agricola"	Saalfeld
Germany	g.Sund Gyn. Kompetenzzentrum	Stralsund
Germany	Kreiskrankenhaus "Johann Kentmann"	Torgau
Germany	Helios Dr. Horst Schmidt Kliniken	Wiesbaden

Sponsors (1)

Lead Sponsor	Collaborator
AGO Research GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time until definitive deterioration (TUDD )	TUDD is defined as time from baseline until the first decrease in EORTC QLQ-C30 score = 10 points (or 20 points) as compared at baseline; EORTC QLQ-C30 is a questionnaire regarding Quality of Life specialized for Cancer with points for each of the 30 questions (1=not at all, 2=a little, 3=quite a bit, 4=very much). Points will be summarized.	from Baseline until 24 months after randomization, assessed up to 54 months at each visit
Secondary	Progression-free survival (PFS)	Progressive disease is based on investigator assessment using RECIST v1.1	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
Secondary	Progression-free survival (PFS) rate at 6 months	Progressive disease is based on investigator assessment using RECIST v1.1	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
Secondary	Response Rate (RR)	RR is based on investigator assessment using RECIST v1.1	from randomization until patients achieving complete response (CR) or partial response (PR) as best overall response, assessed up to 54 months
Secondary	Global Health Status	based on Quality of Life; EORTC QLQ-C30 and EORTC QLQ-OV 28 are questionnaires for Quality of Life with points for each of the 30 or 28 questions (1=not at all, 2=a little, 3=quite a bit, 4=very much). Points will be summarized.	from baseline to end of treatment, assessed up to 54 months at each visit
Secondary	Overall Survival (OS)	regular patient contact during the trila regarding life status	OS is defined as the time from randomization to death from any cause, assessed up to 54 months