Trabectedin/Caelyx vs Cisplatin Hypersensitivity in Relapsed Ovarian Cancer Patients Allergic to Platinum
Condition: Ovarian Neoplasm; Chemotherapeutic Toxicity; Chemotherapy Effect; Chemotherapy-induced Neutropenia; Chemotherapy-induced Nausea and Vomiting
MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Neutropenia; Hypersensitivity; Vomiting
Study type: Observational

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      patients Carboplatin has been replaced by Cisplatin hypersensitivity regimen (CH).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.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        -  Inclusion of 20 patients treated with trabectedin and pegylated liposomal doxorubicin
             after at least one line of previous chemotherapy.

          -  Inclusion of 20 patients treated with cisplatin hypersensitivity and paclitaxel after
             at least one line of previous chemotherapy

          -  All patients treated at Oslo University Hospital, Dept. Gyn. Oncology.
      
Keywords: Ovarian cancer; Pegylated Liposomal Doxorubicin; Trabectedin; Cisplatin hypersensitivity; Paclitaxel