Clinical trial NCT01991210: A Study of DNIB0600A in Comparison With Pegylated Liposomal Doxorubicin (PLD) in Participants With Platinum-Resistant Ovarian Cancer (PROC)
Official title: A Randomized, Open-Label, Multicenter, Phase II Trial Evaluating the Safety and Activity of DNIB0600A Compared to Pegylated Liposomal Doxorubicin Administered Intravenously to Patients With Platinum-Resistant Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ovarian Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2013-11-25
Enrollment: 95
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: This randomized, multicenter, open-label study will evaluate the safety and efficacy of DNIB0600A (RO5541081) in comparison with PLD in participants with PROC, primary peritoneal cancer or fallopian tube cancer. Participants will be randomized to receive either DNIB0600A 2.4 milligrams per kilogram (mg/kg) intravenously (IV) every 3 weeks or PLD 40 milligrams per meter-squared (mg/m\^2) IV every 4 weeks.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically documented epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
* Advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer that has progressed or relapsed during or within 6 months after the most recent treatment with a platinum-containing chemotherapy regimen and for whom PLD is appropriate therapy
* No more than 1 prior cytotoxic chemotherapy regimens for the treatment of PROC and not more than 2 total regimens (defined as any therapy \[approved or investigational\] with intent to treat the ovarian cancer)
* Adequate hematologic, renal and liver function
* Willing and able to perform a patient-reported outcome (PRO) survey (including the possibility of using an electronic PRO device)
* For women of childbearing potential, agreement to use 1 highly effective form of contraception as defined by protocol through the course of study treatment and for 6 months after the last dose of study treatment

Exclusion Criteria:

* Primary platinum-refractory disease defined as disease progression during or within 2 months of a first-line, platinum-containing chemotherapy regimen
* Anti-tumor therapy, including chemotherapy, biologic, experimental, or hormonal therapy, within 4 weeks prior to Day 1
* Palliative radiation within 2 weeks prior to Day 1
* Prior anthracycline therapy, including prior treatment with PLD (for example, Doxil®, Caelyx®, or Lipodox®) in any setting (for example, in combination with carboplatin or as a single agent)
* Prior treatment with NaPi2b or SCL34A2 targeted therapy
* Major surgical procedure within 4 weeks prior to Day 1
* Current Grade greater than (\>) 1 toxicity (except alopecia and anorexia) from prior therapy or Grade \>1 neuropathy from any cause
* Left ventricular ejection fraction defined by multigated acquisition (MUGA)/echocardiogram below the institutional lower limit of normal
* Evidence of significant, uncontrolled, concomitant disease that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease or significant pulmonary disease
* Known active infection, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (within 4 weeks prior to Cycle 1, Day 1)
* Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
* Presence of positive test results for hepatitis B or hepatitis C as detailed in the protocol
* Known history of HIV seropositive status
* Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix, squamous carcinoma of the skin, adequately controlled limited basal cell skin cancer, or synchronous primary endometrial cancer or prior primary endometrial cancer
* Untreated or active central nervous system metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)
* Pregnancy or breastfeeding
* Known history of NaPi2b deficiency (for example, congenital alveolar microlithiasis or testicular microlithiasis)
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
* Metabolic dysfunction, physical examination finding, or clinical laboratory find giving reasonable suspicion of a disease or condition that contraindicated use of an investigational drug or may render the participant at high risk from treatment complications

Primary outcomes:
measure: Progression-free Survival According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: From baseline up to disease progression or death within 30 days of last study drug administration (overall up to approximately 2.5 years)
Secondary outcomes:
measure: Percentage of Participants With Objective Response According to RECIST v1.1
timeFrame: From baseline up to 30 days of last study drug administration (overall up to approximately 2.5 years)
measure: Duration of Objective Response
timeFrame: From occurrence of a documented objective response until relapse or death from any cause (overall up to approximately 2.5 years)
measure: Overall Survival (OS)
timeFrame: From baseline up to death from any cause (overall up to approximately 2.5 years)
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: From baseline up to 30 days of last study drug administration (overall up to approximately 2.5 years)
measure: Area Under the Concentration-time Curve (AUC) of DNIB0600A
timeFrame: Pre-DNIB0600A infusion, 30 minutes post infusion (infusion length=90 minutes) on Day 1 of each Cycle (1cycle=21 days) (overall up to approximately 2.5 years); Day 8 of Cycle 1; Day 15 of Cycles 1-4
measure: Maximum Concentration (Cmax) of DNIB0600A
timeFrame: Pre-DNIB0600A infusion, 30 minutes post infusion (infusion length=90 minutes) on Day 1 of each Cycle (1cycle=21 days) (overall up to approximately 2.5 years); Day 8 of Cycle 1; Day 15 of Cycles 1-4
measure: Clearance (CL) of DNIB0600A
timeFrame: Pre-DNIB0600A infusion, 30 minutes post infusion (infusion length=90 minutes) on Day 1 of each Cycle (1cycle=21 days) (overall up to approximately 2.5 years); Day 8 of Cycle 1; Day 15 of Cycles 1-4
measure: Elimination Half-life (t1/2) of DNIB0600A
timeFrame: Pre-DNIB0600A infusion, 30 minutes post infusion (infusion length=90 minutes) on Day 1 of each Cycle (1cycle=21 days) (overall up to approximately 2.5 years); Day 8 of Cycle 1; Day 15 of Cycles 1-4
measure: Volume of Distribution at Steady State (Vss) of DNIB0600A
timeFrame: Pre-DNIB0600A infusion, 30 minutes post infusion (infusion length=90 minutes) on Day 1 of each Cycle (1cycle=21 days) (overall up to approximately 2.5 years); Day 8 of Cycle 1; Day 15 of Cycles 1-4
measure: Percentage of Participants With Anti-therapeutic Antibodies (ATAs) Against DNIB0600A
timeFrame: Pre-DNIB0600A infusion on Day 1 of Cycles 1-4 (1cycle=21 days), at approximately 15-30 days after last infusion administration (overall up to approximately 2.5 years)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph'S Hospital & Medical Center
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth Research Institute - Pima Center
state: Arizona
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists.
state: Florida
city: Covington
country: United States
facility: Hematology & Oncology Associates
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Uni; Oncology Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Inst.
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Oklahoma City
country: United States
facility: Oklahoma University Health Sciences Center
state: Oklahoma
city: Tualatin
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Pittsburgh
country: United States
facility: Magee Womens Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Women & Infants Hospital
state: Rhode Island
city: Germantown
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Liège
country: Belgium
facility: CHU Sart-Tilman
city: London
country: Canada
facility: London Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Chum Hopital Notre Dame; Centre D'Oncologie
state: Quebec
city: Lyon
country: France
facility: Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: HOPITAL TENON; Cancerologie Medicale
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Bialystok
country: Poland
facility: Bialostockie Centrum Onkologi
city: Gdansk
country: Poland
facility: Wojewodzkie Centrum Onkologii
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny Centralny Szpital Kliniczny MON
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron; Servicio de Neumologia
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Sutton, Surrey
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
city: Wirral
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Banerjee S, Oza AM, Birrer MJ, Hamilton EP, Hasan J, Leary A, Moore KN, Mackowiak-Matejczyk B, Pikiel J, Ray-Coquard I, Trask P, Lin K, Schuth E, Vaze A, Choi Y, Marsters JC, Maslyar DJ, Lemahieu V, Wang Y, Humke EW, Liu JF. Anti-NaPi2b antibody-drug conjugate lifastuzumab vedotin (DNIB0600A) compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer in a randomized, open-label, phase II study. Ann Oncol. 2018 Apr 1;29(4):917-923. doi: 10.1093/annonc/mdy023.