A Crossover Bioequivalence Study of Intravenously Administered ATI0918 and DOXIL/CAELYX in Patients With Ovarian Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to find the answers to the following research question(s): 1. Is the study drug equivalent to the approved drug, Doxil/Caelyx, and does it act the same way in the body as the approved drug? ATI-0918 is believed to be a generic of Doxil/Caelyx and this is what the study is trying to prove. All people who participate in this study will receive the research study medication (ATI-0918) and Doxil/Caelyx in addition to best supportive care (treatment for symptoms). The study drug being tested in this study works the same as the FDA (government) approved drug doxorubicin HCl. ATI-0918 is a generic (the same) formulation of doxorubicin HCl being delivered (given to the patient).

Official Title
-----------------
A Phase 1, Single-blind, Randomized, Two-way, Crossover Bioequivalence Study of Intravenously Administered ATI 0918 in Patients With Ovarian Cancer That Has Progressed or Recurred After Platinum-based Chemotherapy

Conditions
-----------------
Ovarian Cancer, Malignant Female Reproductive System Neoplasm, Cancer, Ovarian Tumor, Ovarian Epithelial Cancer Recurrent

Intervention / Treatment
-----------------
* Drug: DOXIL/CAELYX
* Drug: ATI-0918


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have histologically confirmed ovarian cancer that is potentially sensitive to DOXIL/CAELYX Have disease progression or recurrence after a maximum of 2 prior chemotherapies, one of which was platinum based. Be DOXIL/CAELYX treatment naïve Have a normal left ventricular ejection fraction (LVEF) based on institutional ranges. Have an Eastern Cooperative Oncology Group (ECOG) performance status of </= 2 Have an estimated life expectancy of ≥ 3 months Be >/= 18 and </= 70 years of age Sign a written Institutional Review Board (IRB)-approved informed consent form Have a negative pregnancy test, if patient is of child-bearing potential Have acceptable liver function: Bilirubin </= upper limit of normal (ULN) AST (SGOT), ALT (SGPT) and Alkaline phosphatase </= 1.5 times upper limit of normal Have acceptable renal function: Serum creatinine within normal limits, OR calculated creatinine clearance >/= 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. Have acceptable hematologic status: Neutrophils >/= 1500 cells/mm3 Platelet count >/= 100,000 (plt/mm3) Hemoglobin >/= 9 g/dL Have acceptable coagulation status: Prothrombin time (PT) or International Normalized Ratio (INR) within 1.5 × ULN Partial thromboplastin time (PTT) within 1.5 × ULN Agree to use effective contraceptive methods during the study (nonsterile patients of childbearing potential) Exclusion Criteria: Have New York Heart Association (NYHA) Class III or IV cardiac disease, myocardial infarction within the past 6 months prior to Day 1, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG) or during Cardiac Stress Testing within 14 days prior to Day 1 Have received > 250 mg/m2 of doxorubicin or equivalent as other anthracyclines or similar compounds Have received prior treatment with DOXIL/CAELYX Have received radiotherapy to the mediastinal area or concomitant therapy with other potentially cardiotoxic agents Have seizure disorders requiring anticonvulsant therapy Have known brain metastases (unless previously treated and well controlled for a period of >/= 3 months) Have severe chronic obstructive pulmonary disease with hypoxemia Have had major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1 Have an active, uncontrolled bacterial, viral, fungal, or other opportunistic infections requiring systemic therapy Are pregnant or nursing. NOTE: Nonsterile women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Have received treatment with radiation therapy, surgery, chemotherapy, or investigational therapy within one month prior to study entry (6 weeks for nitrosoureas or Mitomycin C). Have received radiation therapy to >25% of her total bone marrow during her lifetime Are unwilling or unable to comply with procedures required in this protocol Have known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C Have a serious nonmalignant disease (e.g., hydronephrosis, liver failure, significantly impaired hepatic function, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor Are currently receiving any other investigational agent Have exhibited allergic reactions to doxorubicin or a similar structural compound

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DOXIL/CAELYX or Doxorubicin Hydrochloride (Lipspome)<br>Current Standard of care and/or reference product in Europe (Caelyx) and US (Doxorubicin Hydrochloride (Liposome) and Doxil) | Drug: DOXIL/CAELYX<br> <br> * Other names: Liposomal doxorubicin hydrochloride;|
| Experimental: ATI-0918<br>Investigational drug arm which will be compared to Doxil/Caelyx and Hydrochloride Doxorubicin (Liposome) arms for bioequivalence analysis | Drug: ATI-0918<br> <br> * Other names: liposomal doxorubicin hydrochloride;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of AUC in a single dose of ATI0918 vs single dose of Doxil/Caelyx | The primary objective of this study is to determine the pharmacokinetic equivalence of ATI-0918 and DOXIL/CAELYX as a single dose in patients with ovarian cancer. The outcome measure will be determined by analyzing PK data from drawn from each patient at pre-specified time points and calculating Area under the curve (AUC) and Peak Plasma Concentration (Cmax)to determine % variability between ATI0918 and Doxil/Caelyx within each patient. | pre, 30 min + pre, 0, .50, 1, 2, 4, 6, 24, 48, 72, 120, 168, 216 hour post infusion for 2 Cycles (Cycle is defined as 28 days) | 
| Comparison of Cmax in a single dose of ATI0918 vs single dose of Doxil/Caelyx | The primary objective of this study is to determine the pharmacokinetic equivalence of ATI-0918 and DOXIL/CAELYX as a single dose in patients with ovarian cancer. The outcome measure will be determined by analyzing PK data from drawn from each patient at pre-specified time points and calculating Area under the curve (AUC) and Peak Plasma Concentration (Cmax)to determine % variability between ATI0918 and Doxil/Caelyx within each patient. | pre, 30 min + pre, 0, .50, 1, 2, 4, 6, 24, 48, 72, 120, 168, 216 hour post infusion for 2 Cycles (Cycle is defined as 28 days) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Doxil generic, Caelyx generic, generic treatment, ovarian cancer, ovary, progressed, recurred cancer, platinum based therapy