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Ovarian NeoplasmsPhase 3NCT01846611

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

A Phase 3 study testing Trabectedin, DOXIL and Dexamethasone in people with Ovarian Neoplasms and Peritoneal Neoplasms, run by Janssen Research & Development, LLC at 138 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Trabectedin, DOXIL and Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
581 participants
Where
138 sitesin 10 countries
Study dates
16 Oct 2013to 16 Nov 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 13Show fewer
  • Participants no longer need to be 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

Who cannot join

  • 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
  • Participants who had a prior exposure to trabectedin or hypersensitivity to any of the excipients will not be excluded from receiving single-agent Doxil
  • 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)
  • Participants unwilling or unable to have a central venous catheter placed will not be excluded from receiving single-agent Doxil
  • Pregnant or breast-feeding
Show all 14Show fewer
  • 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 therapy
  • Known allergies, hypersensitivity, or intolerance to Doxil, dexamethasone, or their excipients
  • 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 abnormalities
  • 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

Trial locations and contacts

138 sites in 10 countries.

138 sites in 10 countries

United States75 sites

  • Study site

    Abington, Pennsylvania

  • Study site

    Akron, Ohio

  • Study site

    Annandale, Virginia

  • Study site

    Atlanta, Georgia

  • Study site

    Austin, Texas

  • Study site

    Bedford, Texas

  • Study site

    Birmingham, Alabama

  • Study site

    Brightwaters, New York

  • Study site

    Charleston, South Carolina

  • Study site

    Chicago, Illinois

  • Study site

    Cincinnati, Ohio

  • Study site

    Cleveland, Ohio

  • Study site

    Columbia, Missouri

  • Study site

    Columbus, Ohio

  • Study site

    Covington, Louisiana

  • Study site

    Dallas, Texas

  • Study site

    Detroit, Michigan

  • Study site

    Duluth, Minnesota

  • Study site

    Edina, Minnesota

  • Study site

    Englewood, Colorado

  • Study site

    Fort Myers, Florida

  • Study site

    Fort Worth, Texas

  • Study site

    Green Bay, Wisconsin

  • Study site

    Greenbrae, California

  • Study site

    Greenville, South Carolina

  • Study site

    Hackensack, New Jersey

  • Study site

    Hawthorne, New York

  • Study site

    Hot Springs, Arkansas

  • Study site

    Houston, Texas

  • Study site

    Indianapolis, Indiana

  • Study site

    Jacksonville, Florida

  • Study site

    Kansas City, Missouri

  • Study site

    La Jolla, California

  • Study site

    Lansing, Michigan

  • Study site

    Los Angeles, California

  • Study site

    Louisville, Kentucky

  • Study site

    Madison, Wisconsin

  • Study site

    Miami, Florida

  • Study site

    Milwaukee, Wisconsin

  • Study site

    Morristown, New Jersey

  • Study site

    Nashville, Tennessee

  • Study site

    New Britain, Connecticut

  • Study site

    New Brunswick, New Jersey

  • Study site

    New Haven, Connecticut

  • Study site

    New Orleans, Louisiana

  • Study site

    New York, New York

  • Study site

    Newport News, Virginia

  • Study site

    Orange, California

  • Study site

    Park Ridge, Illinois

  • Study site

    Phoenix, Arizona

  • Study site

    Pinehurst, North Carolina

  • Study site

    Pittsburgh, Pennsylvania

  • Study site

    Portland, Oregon

  • Study site

    Providence, Rhode Island

  • Study site

    Roanoke, Virginia

  • Study site

    Sacramento, California

  • Study site

    Salt Lake City, Utah

  • Study site

    San Antonio, Texas

  • Study site

    Sarasota, Florida

  • Study site

    Savannah, Georgia

  • Study site

    Scarborough, Maine

  • Study site

    Scottsdale, Arizona

  • Study site

    Sedona, Arizona

  • Study site

    Spokane, Washington

  • Study site

    St. Petersburg, Florida

  • Study site

    Stamford, Connecticut

  • Study site

    Summit, New Jersey

  • Study site

    Tampa, Florida

  • Study site

    The Woodlands, Texas

  • Study site

    Tucson, Arizona

  • Study site

    Tulsa, Oklahoma

  • Study site

    Vancouver, Washington

  • Study site

    Wauwatosa, Wisconsin

  • Study site

    Webster, Texas

  • Study site

    Worcester, Massachusetts

Other trials in United States

Russia16 sites

  • Study site

    Arkhangelsk

  • Study site

    Chelyabinsk

  • Study site

    Ivanovo

  • Study site

    Kirov

  • Study site

    Krasnodar

  • Study site

    Moscow

  • Study site

    Nal'chik

  • Study site

    Nizhny Novgorod

  • Study site

    Omsk

  • Study site

    Orenburg

  • Study site

    Pyatigorsk

  • Study site

    Ryazan

  • Study site

    Saint Petersburg

  • Study site

    Sochi

  • Study site

    Ufa

  • Study site

    Yaroslavl

Other trials in Russia

Australia10 sites

  • Study site

    Adelaide

  • Study site

    Ballarat

  • Study site

    Brisbane

  • Study site

    Gosford

  • Study site

    Parkville

  • Study site

    Subiaco

  • Study site

    Toorak Gardens

  • Study site

    Townsville

  • Study site

    Wodonga

  • Study site

    Woodville

Other trials in Australia

Israel10 sites

  • Study site

    Beersheba

  • Study site

    Haifa

  • Study site

    Holon

  • Study site

    Jerusalem

  • Study site

    Kfar Saba

  • Study site

    Petah Tikva

  • Study site

    Ramat Gan

  • Study site

    Rehovot

  • Study site

    Tel Aviv

  • Study site

    Tsrifin

Other trials in Israel

United Kingdom8 sites

  • Study site

    Bebington

  • Study site

    Glasgow

  • Study site

    Guildford

  • Study site

    London

  • Study site

    Maidstone

  • Study site

    Manchester

  • Study site

    Plymouth

  • Study site

    Swansea

Other trials in United Kingdom

South Africa6 sites

  • Study site

    Cape Town

  • Study site

    Durban

  • Study site

    eManzimtoti

  • Study site

    Johannesburg

  • Study site

    Port Elizabeth

  • Study site

    Pretoria

Other trials in South Africa

Poland5 sites

  • Study site

    Bydgoszcz

  • Study site

    Gdansk

  • Study site

    Lublin

  • Study site

    Poznan

  • Study site

    Warsaw

Other trials in Poland

China4 sites

  • Study site

    Guangzhou

  • Study site

    Jinan

  • Study site

    Shanghai

  • Study site

    Shenyang

Other trials in China

New Zealand2 sites

  • Study site

    Auckland

  • Study site

    Wellington

Other trials in New Zealand

Switzerland2 sites

  • Study site

    Bern

  • Study site

    Zurich

Other trials in Switzerland

About this study

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

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.

Read the detailed description

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 or until the clinical data cutoff date. 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 or until the clinical cutoff date. As of Amendment 6, no new participants will be randomized to study treatment, and treatment with trabectedin should be immediately discontinued for participants assigned to Arm A (trabectedin+DOXIL). All study participants (Arm A or Arm B) currently on study who, in the opinion of the investigator, are deriving clinical benefit may continue treatment with single-agent DOXIL as per the local standard of care.

Being tested
Trabectedin, DOXIL, Dexamethasone
Keywords
Ovarian neoplasms, Peritoneal neoplasms, Fallopian tube neoplasms, Advanced-relapsed epithelial ovarian cancer, Advanced-relapsed primary peritoneal cancer, Advanced-relapsed fallopian tube cancer, Trabectedin, Yondelis, Doxil, Caelyx, Platinum sensitive, Tthird-line, BRCA, Patient related outcome
Medical subject headings
Ovarian Neoplasms, Peritoneal Neoplasms, Fallopian Tube Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TrabectedinDrug

    1.1 mg/m^2 administered intravenously over approximately 3 hours on Day 1 of each 21-day treatment cycle.

  • DOXILDrug

    30 mg/m^2 administered intravenously over approximately 90 minutes on Day 1 of each 21-day treatment cycle.

  • DexamethasoneDrug

    20 mg administered intravenously on Day 1 of each 21-day treatment cycle approximately 30 minutes prior to study drug infusion.

  • DOXILDrug

    50 mg/m^2 administered intravenously over approximately 90 minutes on Day 1 of each 28-day treatment cycle.

Study groups in NCT01846611
Study groupRoleWhat they receive
Arm A: trabectedin + DOXILExperimentalParticipants will receive DOXIL 30 millgram per meter square (mg/m^2) administered as an intravenous (IV) infusion over approximately 90 minutes followed by trabectedin 1.1 mg/m^2 administered as an IV infusion over approximately 3hours, every 3 weeks. Participants will be pretreated with 20 mg dexamethasone IV (or the IV equivalent) approximately 30 minutes before DOXIL study drug. As of Amendment 6, treatment with trabectedin will be discontinued for participants on treatment with trabectedin and no new participants will receive trabectedin. Participants who, in the opinion of the investigator, are deriving clinical benefit may continue treatment with single-agent DOXIL as per the local standard of care.
Receives: Drug: Trabectedin; Drug: DOXIL; Drug: Dexamethasone
Arm B: DOXILActive comparatorParticipants will receive DOXIL, 50 mg/m^2 administered as an IV infusion over approximately 90 minutes every 4 weeks.
Receives: Drug: DOXIL

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (OS)

    OS is defined as the time between the date of randomization and the date of death. Participants who died, regardless of the cause of death, were considered to have had an event.

    Measured: Up to 4.3 years

Secondary outcomes (2)

  1. Progression-Free Survival (PFS)

    PFS is defined as the time between the date of randomization and the date of disease progression or death. PFS was assessed using the response evaluation criteria in solid tumors (RECIST) Version 1.1. As per criteria progressive disease in case of target lesions means at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). Progressive disease in case of non-target lesions means unequivocal progression of existing non-target lesions. In both cases the appearance of one or more new lesions is also considered progression.

    Measured: Up to 4.3 years

  2. Objective Response Rate (ORR)

    ORR is defined as the percentage of participants with measurable disease achieving a best overall response of either complete response (CR) or partial response (PR) based on RECIST. CR: disappearance of all target and non-target lesions and normalization of tumor marker levels in non-target lesions. PR: at least a 30 percent (%) decrease in the sum of longest diameter (LD) of target lesions or persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.

    Measured: Up to 4.3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 May 2013 (estimated)
  2. Study start16 Oct 2013
  3. Primary completion18 Jan 2018
  4. Study completion16 Nov 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
581 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01846611
Sponsor's protocol ID
CR100983
Other IDs
ET743OVC3006, 2012-004808-34
Status last verified
Mar 2019
First submitted
1 May 2013
Last updated
1 Apr 2019
Data monitoring committee
Yes

Publications

  • Newhouse R, Nelissen E, El-Shakankery KH, Rogozinska E, Bain E, Veiga S, Morrison J. Pegylated liposomal doxorubicin for relapsed epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Jul 5;7(7):CD006910. doi: 10.1002/14651858.CD006910.pub3.

    PubMed 37407274

  • Jones RL, Herzog TJ, Patel SR, von Mehren M, Schuetze SM, Van Tine BA, Coleman RL, Knoblauch R, Triantos S, Hu P, Shalaby W, McGowan T, Monk BJ, Demetri GD. Cardiac safety of trabectedin monotherapy or in combination with pegylated liposomal doxorubicin in patients with sarcomas and ovarian cancer. Cancer Med. 2021 Jun;10(11):3565-3574. doi: 10.1002/cam4.3903. Epub 2021 May 7.

    PubMed 33960681

  • Monk BJ, Herzog TJ, Wang G, Triantos S, Maul S, Knoblauch R, McGowan T, Shalaby WSW, Coleman RL. A phase 3 randomized, open-label, multicenter trial for safety and efficacy of combined trabectedin and pegylated liposomal doxorubicin therapy for recurrent ovarian cancer. Gynecol Oncol. 2020 Mar;156(3):535-544. doi: 10.1016/j.ygyno.2019.12.043. Epub 2020 Jan 8.

    PubMed 31924332

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Trabectedin, DOXIL and Dexamethasone in people with Ovarian Neoplasms and Peritoneal Neoplasms, run by Janssen Research & Development, LLC at 138 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 138 sites in United States, Russia, Australia, Israel, United Kingdom and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: Up to 4.3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01846611, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2019.

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