A Study Comparing the Combination of Trabectedin (YONDELIS) and DOXIL/CAELYX With DOXIL/CAELYX for the Treatment of Advanced-Relapsed Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Study ID

Cancer Related

Healthy Volunteers

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • Zale Lipshy University Hospital
  • Parkland Health & Hospital System

Isabel Villalobos

Principal Investigator
David Miller

Official Title

A Randomized, Open-Label Study Comparing the Combination of YONDELIS and DOXIL/CAELYX With DOXIL/CAELYX Monotherapy for the Treatment of Advanced-Relapsed Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Brief Overview

The purpose of this study is to assess the efficacy and safety of trabectedin+DOXIL as a
third-line chemotherapy regimen (treatment) in patients with platinum-sensitive
advanced-relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer who
received 2 previous lines of platinum-based chemotherapy.


This is a randomized (individuals assigned to study treatment by chance), open - label
(identity of assigned study drug will be known), active - controlled study in adult female
patients with platinum-sensitive advanced - relapsed epithelial ovarian, primary peritoneal,
or fallopian tube cancer who received 2 previous lines of platinum - based chemotherapy.
Approximately 670 participants will be enrolled. Patients will be stratified by 4 criteria
defined in the protocol and randomly assigned in a 1:1 ratio to the trabectedin+DOXIL
combination therapy group (Arm A) or to the DOXIL (pegylated liposomal doxorubicin)
monotherapy group (Arm B). During the treatment phase, patients will receive study drug
infusions according to 21 - day cycles in Arm A and 28 - day cycles in Arm B. Treatment will
continue until the occurrence of disease progression or unacceptable treatment toxicity, or
until 2 cycles after assessment of a complete response (CR). Efficacy assessments will be
evaluated using Response Evaluation Criteria in Solid Tumors. Disease assessments, including
assessments for patients who discontinue treatment for reasons other than disease
progression, will be performed until disease progression, the start of subsequent anticancer
therapy, withdrawal of consent, or the clinical cutoff date. Collection of survival status
will continue until at least 514 deaths have been observed. Serial pharmacokinetic (PK)
samples will be collected in a subset of patients who voluntarily consent to the PK portion
of the study. Safety will be monitored throughout the study. An interim analysis of overall
survival (OS) will be performed after approximately 308 participants have died. The final
analysis of OS will occur when approximately 514 deaths have been observed.

Participant Eligibility

Inclusion Criteria:

- Histologically proven advanced-relapsed epithelial ovarian, primary peritoneal, or
fallopian tube cancer

- Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1

- Received first-line treatment with a platinum-based regimen and had no evidence of
disease progression for >= 6 months after the last dose

- Received second-line treatment with a platinum-based regimen, with progression of
disease after attaining a response

- Progression of disease based on imaging after the second-line platinum-based regimen
(individuals treated with a pegylated liposomal doxorubicin-containing regimen as a
second-line therapy are eligible if subsequent disease progression occurs >=9 months
from the first dose)

- Evidence of measurable disease at screening as evaluated by Response Evaluation
Criteria in Solid Tumors (RECIST) (Version 1.1)

- Able to receive intravenous (IV) dexamethasone or an equivalent IV corticosteroid

- Have a known BRCA 1/2 mutation status (for participants who do not have a known BRCA
1/2 status at screening, a blood sample will be collected to determine the status
with the results available prior to randomization

- Laboratory values within protocol -defined parameters

- Have left ventricular ejection fraction by multigated acquisition scan (MUGA) scan or
2D-ECHO within normal limits for the institution

- Have side effects (except alopecia) of prior treatment resolved to at least Grade 1
according to the National Cancer Institute - Common Terminology Criteria of Adverse
Events (NCICTCAE) (Version 4.0)

- Have a negative urine or serum pregnancy test at screening

- Agrees to protocol-defined use of effective contraception

Exclusion Criteria:

- Diagnosis of ovarian carcinoma with mucinous histology

- Had more than 2 prior lines of systemic therapy. Maintenance therapies and hormonal
therapies are not considered additional lines of therapy

- Prior exposure to trabectedin or hypersensitivity to any of the excipients

- Prior treatment with doxorubicin or other anthracycline at cumulative doses greater
than 300 mg/m2 (calculated using doxorubicin equivalent doses: 1 mg doxorubicin = 1
mg Doxil/Caelyx = 1.8 mg epirubicin = 0.3 mg mitoxantrone = 0.25 mg idarubicin)

- Unwilling or unable to have a central venous catheter placed

- Pregnant or breast-feeding

- Would receive study treatment within 3 weeks from radiation therapy, experimental
therapy, hormonal therapy, prior chemotherapy, or biological therapy; use an invasive
investigational device; or is currently enrolled in an investigational study

- History of another invasive malignancy (except non-metastatic basal cell carcinoma or
squamous cell carcinoma of the skin or cervical carcinoma in situ adequately treated)
unless in remission for >=5 years, or a non - invasive malignancy requiring ongoing

- Known allergies, hypersensitivity, or intolerance to Doxil, dexamethasone, or their

- Known history of central nervous system metastasis

- Known significant chronic liver disease, such as cirrhosis or active hepatitis
(potential participants who test positive for hepatitis B surface antigen or
hepatitis C antibodies are allowed provided they do not have active disease requiring
antiviral therapy)

- Had a myocardial infarct within 6 months before enrollment, New York Heart
Association (NYHA) Class II or greater heart failure, uncontrolled angina, severe
uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or
electrocardiographic evidence of acute ischemic or active conduction system

- Has any of the following medical conditions: uncontrolled diabetes, psychiatric
disorder (including dementia) that prevents compliance with protocol, uncontrolled
seizures, newly diagnosed deep vein thrombosis, active systemic infection that is
likely to interfere with study procedure or results

- Has any condition that, in the opinion of the investigator, would compromise the
well-being of the participant or the study or prevent the participant from meeting or
performing study requirements