Trabectedin/Caelyx vs Cisplatin Hypersensitivity in Relapsed Ovarian Cancer Patients Allergic to Platinum

NCT ID: NCT05512676

Last Updated: 2022-08-23

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-03-07
• Study Completion Date: 2022-08-01

Brief Summary

Observational, clinical study. Intention to include 40 patients (20 patients treated with trabectedin and 20 with cisplatin hypersensitivity) The investigators investigate the role of trabectedin in combination with PLD and cisplatin in treating platinum sensitive ROC being allergic to carboplatin. The investigators focus on adverse events and evaluate if these are tolerable for the patients and further evaluate the measurable treatment effect on the tumor burden.

Detailed Description

INTRODUCTION Trabectedin (Yondelis®) is a tetrahydroisoquinoline alkaloid that is produced synthetically. It acts by interfering with DNA transcription factors, DNA binding proteins, and DNA repair pathways. This results in cell cycle arrest and apoptosis. Trabectedin (T) probably causes DNA double-strand breaks. Trabectedin decreases the level of proangiogenic VEGF, CCL2, and interleucin-6 (IL-6) which indicate that trabectedin is cytotoxic with immune regulatory effects (1).

Since 2007 trabectedin mainly has been used in the treatment of soft tissue sarcomas (1). In meningioma trabectedin has been used in a murine model of ovarian cancer (2). A combined treatment of trabectedin and anti-PD1 antibody produces a synergic antitumor effect (3).

In a phase III international multicentre study the addition of trabectedin to pegylated liposomal doxyrubicin (PLD) (Caelyx) has shown to improve progression free survival and overall response rate compared to PLD alone in second-line treatment of recurrent ovarian cancer (ROC) (4). Trabectedin can replace platinum in clinical settings where there has been serious allergic reaction adverse effect from platinum (Carboplatin) (4). In many of these patients Carboplatin has been replaced by Cisplatin hypersensitivity regimen (CH). In patients with serious side effects to Cisplatin or other factors that impair the treatment of Cisplatin, trabectedin is a good alternative (4).

Trabectedin may also have a therapeutic role in patients with recurrent BRCA mutated ovarian cancer patients (5,6). When combined with PLD, trabectedin improves progression free survival (PFS) and objective response rate (ORR) in the second line-treatment of ROC. The combination led to manageable and non-cumulative overall toxicity with a fewer PLD-associated adverse events (7,8,9).

The majority of patients treated with trabectedin are given the combination with PDL and patients treated with cisplatin have the combination with paclitaxel.

In the present study the investigators will examine the role of trabectedin in combination with PLD and cisplatin in treating platinum sensitive ROC being allergic to carboplatin. The investigators will focus on adverse events and evaluate if these are tolerable for the patients and further evaluate the measurable treatment effect on the tumor burden.

Primary aims:

To investigate if trabectedin in combination with pegylated liposomal doxyrubicin (PLD) is applicable to replace desensitising cisplatin ROC treatment.

Secondary aims:

• Effect on tumor burden (CT by RISK criteria, vaginal ultrasound, CA125).
• Level of adverse effects.
• To calculate the PFS of the two cohorts (trabectedin and cisplatin).
• To calculate cancer specific survival (CSS) of the two cohorts (trabectedin and cisplatin) MATERIAL AND METHODS A description of the indication of treatment and follow-up after treatment with trabectedin in combination with PLD or cisplatin at the Oslo University Hospital (OUS), Department of gynecologic cancer. This study is retrospective and prospective in design. Totally 20 patients treated with trabectedin in combination with PLD and 20 patients with cisplatin will be included in the study.

Platinum sensitive tumors are defined as tumors recurring 6 months or more after previouis platinum treatment. In the study the investigators will mainly include patients having allergic reactions to carboplatin.

Conditions

Ovarian Neoplasm; Chemotherapeutic Toxicity; Chemotherapy Effect; Chemotherapy-induced Neutropenia; Chemotherapy-induced Nausea and Vomiting

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Women with recurrent ovarian cancer and
• allergic reaction to carboplatin or
• other serious side effects to carboplatin

Exclusion Criteria

• Patients not treated with carboplatin previously

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Swedish Orphan Biovitrum

INDUSTRY

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Torbjørn Paulsen

Senior Consultant

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Erik Rokkones, PhD

Role: STUDY_DIRECTOR

Head of Gyn. Onc. Department, Oslo University Hospital

Torbjørn Paulsen, PhD

Role: PRINCIPAL_INVESTIGATOR

Oslo University hospital, Dept. Gyn. Oncology, Norway

Other Identifiers

2015/2167 REK sør-øst B

Identifier Type: -

Identifier Source: org_study_id