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| Name | Class |
|---|---|
| Swedish Orphan Biovitrum | INDUSTRY |
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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.
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 In many of these patients Carboplatin has been replaced by Cisplatin hypersensitivity regimen (CH).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:
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.
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| Measure | Description | Time Frame |
|---|---|---|
| PFS | Progression Free Survival | From date of end of recurrent treatment (date of last cycle) with trabectedin/PLD or cisplatin hypersensitivity/paclitaxel until the date of first documented progression or date of death from any cause whichever came first, assessed up to 130 months. |
| Side effects | Side effects of recurrent treatment from trabectedin/PLD and cisplatin hypersensitivity/paclitaxel. | The side effects are assessed until 28 days after each cycle, up to 8 weeks after last cycle with trabectedin or cisplatin hypersensitivity. Each cycle is 28 days until 6 cycles.. |
| Measure | Description | Time Frame |
|---|---|---|
| Cancer Specific survival (CSS) | Cancer Specific survival | From date of primary diagnosis until date of last observation or death of ovarian cancer, whichever came first, assessed up to 36 years. |
| Drug Interactions |
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Inclusion Criteria:
Exclusion Criteria:
- Patients not treated with carboplatin previously
Only women included
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| Name | Affiliation | Role |
|---|---|---|
| Erik Rokkones, PhD | Head of Gyn. Onc. Department, Oslo University Hospital | Study Director |
| Torbjørn Paulsen, PhD | Oslo University hospital, Dept. Gyn. Oncology, Norway | Principal Investigator |
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The data are saved in individual Case Report Forms in pdf format. All data are encoded in SPSS. An anonymous SPSS File may be distributed on request.
End of 2023
A description of the purpose of data sharing.
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Interactions between trabectedin/PLD or cisplatin hypersensitivity/paclitaxel and other drugs the patients use during recurrent treatment (Examples: antihypertensive drugs, drugs inhibition of CYP450 2C8/3A4). The drugs are defined as mild increase-moderate increase -severe increase, mild decrease, modereate decrease, and severe decrease (6 categories) of trabectedin, PLD, cisplatin hypersensitivity or paclitaxel effect. The categories are obtained from the Drug Interactions Checker at www.drugs.com.
| From date of start recurrent treatment with trabectedin/PLD or cisplatin hypersensitivity/paclitaxel until date of last cycle with trabectedin/PLD or cisplatin hypersens/paclitaxel. The data are assessed at each cycle, 2 weeks after each cycle until 6. |
| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| D014839 | Vomiting |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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