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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: DNIB0600A
* Drug: PLD


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DNIB0600A<br>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<br>* DNIB0600A will be administered at a dose of 2.4 mg/kg IV every 3 weeks.<br>* Other names: RO5541081;|
| Active Comparator: PLD<br>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<br>* PLD will be administered at a dose of 40 mg/m^2 IV every 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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) |