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

NCT ID: NCT01846611

Last Updated: 2019-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 581 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-16
• Study Completion Date: 2018-11-16

Brief 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.

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.

Conditions

Ovarian Neoplasms; Peritoneal Neoplasms; Fallopian Tube Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: trabectedin + DOXIL

Participants 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.

Group Type: EXPERIMENTAL

Trabectedin

Intervention Type: DRUG

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

DOXIL

Intervention Type: DRUG

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

Dexamethasone

Intervention Type: DRUG

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

Arm B: DOXIL

Participants will receive DOXIL, 50 mg/m\^2 administered as an IV infusion over approximately 90 minutes every 4 weeks.

Group Type: ACTIVE_COMPARATOR

DOXIL

Intervention Type: DRUG

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

Interventions

Trabectedin

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

Intervention Type: DRUG

DOXIL

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

Intervention Type: DRUG

Dexamethasone

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

Intervention Type: DRUG

DOXIL

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

Intervention Type: DRUG

Eligibility Criteria

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)
• 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

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
• 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

PharmaMar

INDUSTRY

Sponsor Role: collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Birmingham, Alabama, United States

Phoenix, Arizona, United States

Scottsdale, Arizona, United States

Sedona, Arizona, United States

Tucson, Arizona, United States

Hot Springs, Arkansas, United States

Greenbrae, California, United States

La Jolla, California, United States

Los Angeles, California, United States

Orange, California, United States

Sacramento, California, United States

Englewood, Colorado, United States

New Britain, Connecticut, United States

New Haven, Connecticut, United States

Stamford, Connecticut, United States

Fort Myers, Florida, United States

Jacksonville, Florida, United States

Miami, Florida, United States

Sarasota, Florida, United States

St. Petersburg, Florida, United States

Tampa, Florida, United States

Atlanta, Georgia, United States

Savannah, Georgia, United States

Chicago, Illinois, United States

Park Ridge, Illinois, United States

Indianapolis, Indiana, United States

Louisville, Kentucky, United States

Covington, Louisiana, United States

New Orleans, Louisiana, United States

Scarborough, Maine, United States

Worcester, Massachusetts, United States

Detroit, Michigan, United States

Lansing, Michigan, United States

Duluth, Minnesota, United States

Edina, Minnesota, United States

Columbia, Missouri, United States

Kansas City, Missouri, United States

Hackensack, New Jersey, United States

Morristown, New Jersey, United States

New Brunswick, New Jersey, United States

Summit, New Jersey, United States

Brightwaters, New York, United States

Hawthorne, New York, United States

New York, New York, United States

Pinehurst, North Carolina, United States

Akron, Ohio, United States

Cincinnati, Ohio, United States

Cleveland, Ohio, United States

Columbus, Ohio, United States

Tulsa, Oklahoma, United States

Portland, Oregon, United States

Abington, Pennsylvania, United States

Pittsburgh, Pennsylvania, United States

Providence, Rhode Island, United States

Charleston, South Carolina, United States

Greenville, South Carolina, United States

Nashville, Tennessee, United States

Austin, Texas, United States

Bedford, Texas, United States

Dallas, Texas, United States

Fort Worth, Texas, United States

Houston, Texas, United States

San Antonio, Texas, United States

The Woodlands, Texas, United States

Webster, Texas, United States

Salt Lake City, Utah, United States

Annandale, Virginia, United States

Newport News, Virginia, United States

Roanoke, Virginia, United States

Spokane, Washington, United States

Vancouver, Washington, United States

Green Bay, Wisconsin, United States

Madison, Wisconsin, United States

Milwaukee, Wisconsin, United States

Wauwatosa, Wisconsin, United States

Adelaide, , Australia

Ballarat, , Australia

Brisbane, , Australia

Gosford, , Australia

Parkville, , Australia

Subiaco, , Australia

Toorak Gardens, , Australia

Townsville, , Australia

Wodonga, , Australia

Woodville, , Australia

Guangzhou, , China

Jinan, , China

Shanghai, , China

Shenyang, , China

Beersheba, , Israel

Haifa, , Israel

Holon, , Israel

Jerusalem, , Israel

Kfar Saba, , Israel

Petah Tikva, , Israel

Ramat Gan, , Israel

Rehovot, , Israel

Tel Aviv, , Israel

Ẕerifin, , Israel

Auckland, , New Zealand

Wellington, , New Zealand

Bydgoszcz, , Poland

Gdansk, , Poland

Lublin, , Poland

Poznan, , Poland

Warsaw, , Poland

Arkhangelsk, , Russia

Chelyabinsk, , Russia

Ivanovo, , Russia

Kirov, , Russia

Krasnodar, , Russia

Moscow, , Russia

Nal'chik, , Russia

Nizhny Novgorod, , Russia

Omsk, , Russia

Orenburg, , Russia

Pyatigorsk, , Russia

Ryazan, , Russia

Saint Petersburg, , Russia

Sochi, , Russia

Ufa, , Russia

Yaroslavl, , Russia

Cape Town, , South Africa

Durban, , South Africa

eManzimtoti, , South Africa

Johannesburg, , South Africa

Port Elizabeth, , South Africa

Pretoria, , South Africa

Bern, , Switzerland

Zurich, , Switzerland

Bebington, , United Kingdom

Glasgow, , United Kingdom

Guildford, , United Kingdom

London, , United Kingdom

Maidstone, , United Kingdom

Manchester, , United Kingdom

Plymouth, , United Kingdom

Swansea, , United Kingdom

Countries

United States; Australia; China; Israel; New Zealand; Poland; Russia; South Africa; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37407274 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33960681 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31924332 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ET743OVC3006

Identifier Type: OTHER

Identifier Source: secondary_id

2012-004808-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR100983

Identifier Type: -

Identifier Source: org_study_id