QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer

Comparison of Quality of Life (QoL) Between Trabectedin/PLD and Standard Platinum-based Therapy in Patients With Platinum Sensitive Recurrent Ovarian, Fallopian Tube and Peritoneal Cancer

This is a multicenter, randomized, controlled, open-label study including patients with recurrent, platinum-sensitive, ovarian, peritoneal or fallopian tube cancer.

The main scope of the trial is to evaluate QoL during chemotherapy comparing trabectedin/PLD with other standard platinum-based chemotherapy in platinum-sensitive disease.

This is a multicenter, randomized, controlled, open-label study including patients with recurrent, platinum-sensitive, ovarian, peritoneal or fallopian tube cancer.

The main scope of the trial is to evaluate QoL during chemotherapy comparing trabectedin/PLD with other standard platinum-based chemotherapy in platinum-sensitive disease.

Patients with recurrent, platinum-sensitive, ovarian, fallopian tube and peritoneal cancer will be stratified according to surgery for relapse (R0 vs. R1/2 resection) vs. no surgery in the same setting and age (< 75 years vs. ≥ 75 years), and randomized 1:1 to receive either trabectedin/PLD (Arm A) or one of 3 platinum-based standard therapies without bevacizumab (Arm B, "other standard therapy"). In case of randomization to "other standard therapy", the investigator has the choice between carboplatin/PLD, carboplatin/gemcitabine and carboplatin/paclitaxel. Patients in both treatment arms will receive chemotherapy up for 6 cycles or until disease progression (PD), unacceptable toxicities or patient's wish to stop therapy, whichever occurs first.

Inclusion criteria

1. Women aged ≥ 18 years

2. Patients with histologically confirmed diagnosis of epithelial ovarian cancer, primary peritoneal carcinoma or fallopian tube cancer who received ≥1 prior chemotherapy

3. Patients must be eligible for platin-containing therapy; Patient is defined as platin-sensitive when considered for platin-containing therapy by the investigator. The time frame from end of prior therapy until disease progression alone is not pivotal for study participation. Patients without a platin-containing regimen in the previous line who are also eligible for platin-containing regime are also appropriate for participation

4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

5. Adequate baseline organ function as defined as

   • Leucocytes > 3.0 x 109/l
   • Platelet count > 100 x 109/l
   • Absolute neutrophil count (ANC) ≥1500/mm3
   • Haemoglobin ≥ 9 g/dl
   • Alkaline Phosphatase (AP) ≤ 2.5 × ULN (consider hepatic isoenzymes 5 nucleotidase or gamma glutamyl transpeptidase (GGT), if the elevation could be osseous in origin)
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
   • Creatinine-Clearance ≥ 60 ml/min (MDRD formula or Cockroft & Gault formula)
   • Serum creatinine ≤ 1.5 mg/dl
   • Creatine phosphokinase (CPK) ≤ 2.5 × ULN
   • Total bilirubin < ULN

6. Women of childbearing potential should use contraceptives or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication or be surgically sterile.

7. Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 50% as determined by echocardiogram

8. Patients must provide written informed consent prior to performance of study specific procedures or assessments, and must be willing to comply with treatment and follow up assessments and procedures.

Exclusion criteria

1. Only malignancies, which influence the prognosis
2. Any unstable or serious concurrent condition (e.g. active infection requiring systemic therapy).
3. Chemotherapy or radiation therapy or tumor embolization within 2 weeks prior to the first dose of study drug or planned during study participation.
4. Patients who have refractory disease. Refractory disease is defined if relapse occurs <4 months after beginning of platin-containing therapy.
5. Hypersensitivity to the active substance or to any of the excipients of study drug
6. Findings from ECG and/or assessment of LVEF which indicate an anthracycline-related cardiotoxic process which contradicts administration of liposomal doxorubicin in accordance with the requirements of the SmPC of PLD.
7. Biological therapy, immunotherapy, hormonal therapy or treatment with an investigational agent within 14 days (for bevacizumab, 30 days) prior to the first dose of study drug.
8. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
9. Participation in another clinical study with experimental therapy within the 30 days before start of and during treatment. Participation in a non-interventional study should be discussed with sponsor and NC beforehand.
10. Patients in a closed institution according to an authority or court decision (AMG § 40, Abs. 1 No. 4)
11. Patients who are depending on the sponsor/CRO or investigational site as well as on the investigator.
12. Pregnancy or lactation period, or planning to become pregnant within 7 months after the end of treatment.