A Study of DNIB0600A in Comparison With Pegylated Liposomal Doxorubicin (PLD) in Participants With Platinum-Resistant Ovarian Cancer (PROC)

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

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.

Study Overview

• Status: Terminated
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: DNIB0600A; Drug: PLD

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
  • Liège, Belgium, 4000
    • CHU Sart-Tilman
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Centre
    • Toronto, Ontario, Canada, M4X 1K9
      • Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Chum Hopital Notre Dame; Centre D'Oncologie
• France
  • Lyon, France, 69008
    • Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
  • Paris, France, 75970
    • HOPITAL TENON; Cancerologie Medicale
  • Paris, France, 75908
    • Hôpital Européen Georges Pompidou
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Poland
  • Bialystok, Poland, 15-027
    • Bialostockie Centrum Onkologi
  • Gdansk, Poland, 80-219
    • Wojewodzkie Centrum Onkologii
  • Warszawa, Poland, 04-141
    • Wojskowy Instytut Medyczny Centralny Szpital Kliniczny MON
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron; Servicio de Neumologia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28050
    • HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute
  • Manchester, United Kingdom, M20 3BG
    • Christie Hospital
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden Hospital
  • Sutton, Surrey, United Kingdom, SM2 5PT
    • Royal Marsden NHS Foundation Trust
  • Wirral, United Kingdom, L63 4JY
    • The Clatterbridge Cancer Centre NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital & Medical Center
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute - Pima Center
  • California
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center
  • Florida
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists.
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Hematology & Oncology Associates
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Uni; Oncology Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Inst.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Health Sciences Center
  • Oregon
    • Tualatin, Oregon, United States, 97062
      • Northwest Cancer Specialists, P.C.
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee Womens Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women & Infants Hospital
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Sarah Cannon Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DNIB0600A; DNIB0600A will be administered on Day 1 of each cycle (1 cycle = 21 days) until significant toxicity, disease progression, or withdrawal from the study (overall up to approximately 2.5 years).	Drug: DNIB0600A; DNIB0600A will be administered at a dose of 2.4 mg/kg IV every 3 weeks.; Other Names: RO5541081
Active Comparator: PLD; PLD will be administered on Day 1 of each cycle (1 cycle = 28 days) until significant toxicity, disease progression, or withdrawal from the study (overall up to approximately 2.5 years).	Drug: PLD; PLD will be administered at a dose of 40 mg/m^2 IV every 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free Survival According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	From baseline up to disease progression or death within 30 days of last study drug administration (overall up to approximately 2.5 years)

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Objective Response According to RECIST v1.1	From baseline up to 30 days of last study drug administration (overall up to approximately 2.5 years)
Duration of Objective Response	From occurrence of a documented objective response until relapse or death from any cause (overall up to approximately 2.5 years)
Overall Survival (OS)	From baseline up to death from any cause (overall up to approximately 2.5 years)
Percentage of Participants With Adverse Events (AEs)	From baseline up to 30 days of last study drug administration (overall up to approximately 2.5 years)
Area Under the Concentration-time Curve (AUC) of DNIB0600A	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
Maximum Concentration (Cmax) of DNIB0600A	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
Clearance (CL) of DNIB0600A	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
Elimination Half-life (t1/2) of DNIB0600A	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
Volume of Distribution at Steady State (Vss) of DNIB0600A	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
Percentage of Participants With Anti-therapeutic Antibodies (ATAs) Against DNIB0600A	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)

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2014
• Primary Completion (Actual): August 17, 2016
• Study Completion (Actual): August 17, 2016

Study Registration Dates

• First Submitted: November 15, 2013
• First Submitted That Met QC Criteria: November 21, 2013
• First Posted (Estimate): November 25, 2013

Study Record Updates

• Last Update Posted (Actual): August 21, 2017
• Last Update Submitted That Met QC Criteria: August 17, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: GO28609; 2012-005776-34 (EudraCT Number)