Clinical trial NCT01846611: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ovarian Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
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
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: PharmaMar
First posted: 2013-05-03
Enrollment: 581
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 4.3 years
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Up to 4.3 years
measure: Objective Response Rate (ORR)
timeFrame: Up to 4.3 years
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Sedona
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Hot Springs
country: United States
state: Arkansas
city: Greenbrae
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Orange
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Englewood
country: United States
state: Colorado
city: New Britain
country: United States
state: Connecticut
city: New Haven
country: United States
state: Connecticut
city: Stamford
country: United States
state: Connecticut
city: Fort Myers
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Saint Petersburg
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Savannah
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Park Ridge
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Louisville
country: United States
state: Kentucky
city: Covington
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: Scarborough
country: United States
state: Maine
city: Worcester
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Lansing
country: United States
state: Michigan
city: Duluth
country: United States
state: Minnesota
city: Edina
country: United States
state: Minnesota
city: Columbia
country: United States
state: Missouri
city: Kansas City
country: United States
state: Missouri
city: Hackensack
country: United States
state: New Jersey
city: Morristown
country: United States
state: New Jersey
city: New Brunswick
country: United States
state: New Jersey
city: Summit
country: United States
state: New Jersey
city: Brightwaters
country: United States
state: New York
city: Hawthorne
country: United States
state: New York
city: New York
country: United States
state: New York
city: Pinehurst
country: United States
state: North Carolina
city: Akron
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Tulsa
country: United States
state: Oklahoma
city: Portland
country: United States
state: Oregon
city: Abington
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Providence
country: United States
state: Rhode Island
city: Charleston
country: United States
state: South Carolina
city: Greenville
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Bedford
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: The Woodlands
country: United States
state: Texas
city: Webster
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Annandale
country: United States
state: Virginia
city: Newport News
country: United States
state: Virginia
city: Roanoke
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Vancouver
country: United States
state: Washington
city: Green Bay
country: United States
state: Wisconsin
city: Madison
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
city: Wauwatosa
country: United States
state: Wisconsin
city: Adelaide
country: Australia
city: Ballarat
country: Australia
city: Brisbane
country: Australia
city: Gosford
country: Australia
city: Parkville
country: Australia
city: Subiaco
country: Australia
city: Toorak Gardens
country: Australia
city: Townsville
country: Australia
city: Wodonga
country: Australia
city: Woodville
country: Australia
city: Guangzhou
country: China
city: Jinan
country: China
city: Shanghai
country: China
city: Shenyang
country: China
city: Beer Sheva
country: Israel
city: Haifa
country: Israel
city: Holon
country: Israel
city: Jerusalem
country: Israel
city: Kfar Saba
country: Israel
city: Petah Tikva
country: Israel
city: Ramat-Gan
country: Israel
city: Rehovot
country: Israel
city: Tel Aviv
country: Israel
city: Zerifin
country: Israel
city: Auckland
country: New Zealand
city: Wellington
country: New Zealand
city: Bydgoszcz
country: Poland
city: Gdańsk
country: Poland
city: Lublin
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Arkhangelsk
country: Russian Federation
city: Chelyabinsk
country: Russian Federation
city: Ivanovo
country: Russian Federation
city: Kirov
country: Russian Federation
city: Krasnodar
country: Russian Federation
city: Moscow N/a
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nalchik
country: Russian Federation
city: Nizhniy Novgorod
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: Omsk
country: Russian Federation
city: Orenburg
country: Russian Federation
city: Pyatigorsk
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Saint-Petersburg,
country: Russian Federation
city: Sochi
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Ufa
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Amanzimtoti
country: South Africa
city: Cape Town
country: South Africa
city: Durban
country: South Africa
city: Johannesburg
country: South Africa
city: Port Elizabeth
country: South Africa
city: Pretoria
country: South Africa
city: Bern
country: Switzerland
city: Zurich
country: Switzerland
city: Bebington
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Guilford
country: United Kingdom
city: London
country: United Kingdom
city: Maidstone
country: United Kingdom
city: Manchester
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Swansea
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.