A Phase 1 Trial of ABI-011 in Patients With Advanced Solid Tumors or Lymphomas

Study Overview
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Brief Summary
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The purpose of this study is to determine the MTD and/or RP2D of ABI-011 when administered by IV on Day 1, Day 8 and Day 15 with one week of rest for patients with advanced solid tumor malignancies and lymphomas.

Detailed Description
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Dose limiting toxicities (DLT), maximum tolerated dose (MTD)

Official Title
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A Phase I Trial of ABI-011 Administered Weekly in Patients With Advanced Solid Tumors or Lymphomas

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: ABI-011


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be equal or greater 18 years of age ECOG performance status less than or equal to 2 (Appendix 2) Pts. must be willing and able to sign informed consent Cytologically or histologically confirmed solid tumor malignancy or lymphoma for which no standard approved therapy is available. Patients should have accessible tumor lesions amendable to 2 serial biopsies which would not put the patient or their treatment at risk Pt. agrees and is willing to provide 2 serial tumor biopsies(optional on first phase, mandatory on 2nd phase) During the dose escalation phase, measurable or non-measurable disease as defined by RECIST criteria. At 2nd phase, only patients with measurable disease Life expectancy of equal or greater than 12 weeks All AEs of any prior chemotherapy, surgery or radiotherapy, must have resolved to grade equal to or less than 1 The following laboratory results must be present within 14 days of initial ABI-011 administration Hemoglobin greater or equal to 9g/dL Absolute neutrophils count(ANC)greater or equal to 1.5 x 10^9/L Platelet count is greater or equal to 100 x 10^9/L Serum bilirubin less than or equal to 1.5 x upper limit of normal (ULN) Aspartate transaminase (AST) and alanine transaminase (ALT)is less than or equal to 2.5 ULN(except if liver metastases are present; then values must be less than or equal to 5 x ULN) Potassium, corrected calcium and magnesium WNL Serum Creatinine less than or equal to 1.5 x ULN Activated aPTT,PT,INR,WNL WNL levels : Troponin I and T, CK-MB,BNP At least one measurable lesion should be evaluable (DCE-MRI eligibility criteria)and meet at least one of the criteria below: At least one measurable lesions should be at least 3 cm in diameter and should not be near the diaphragm or mediastinum Lesions should be solid masses that enhance with contrast, without signs of calcification on the most recent computed tomography (CT) or magnetic resonance (MRI)scan Pts. must be willing to practice contraceptive methods for the duration of the study and for one month following study completion. Female patients must be postmenopausal, surgically sterile or they must agree to use acceptable methods of birth control. Male patients must be surgically sterile or agree to use an acceptable method of contraception. Women of childbearing potential must have a negative serum pregnancy test(B-hCG)within 72 hours prior to first study drug administration Exclusion Criteria: Inability to comply with study and follow-up procedures Women who are pregnant or lactating Treatment with chemotherapy, hormonal therapy(except leuprolide for prostate cancer), immunotherapy, biologic therapy, or radiation therapy as cancer therapy within 4 weeks before initiation of study treatment. Six weeks should have elapsed if prior chemotherapy treatment included nitrosoureas or mitomycin C Pts. who have received antibody-based therapies within 28 days or 5 half-lives of the agent, whichever time period is longer Major surgery within 6 weeks before first study drug administration Prior treatment with tumor vascular disruptive agents Any uncontrolled medical or psychiatric risk factors Central nervous system(CNS)metastases. History of diabetic retinopathy. All patients must be evaluated by an ophthalmologist prior to study treatment Any history of myopathy, either peripheral or cardiac Current use of medications that may have the potential of QTc prolongation History of allergy or hypersensitivity to any compound of the ABI-011 formulation Active uncontrolled bacterial, viral, or fungal infection, requiring systemic therapy Pt.has known infection with human immunodeficiency virus (HIV),or known chronic Hepatitis B or Hepatitis C Inability to be venipunctured and/or tolerate venous access History of other carcinoma within past 5 years Pts. requiring therapeutic anticoagulation with either coumadin or low molecular weight heparin or with history of any bleeding diathesis. Low dose aspirin and low dose coumadin for catheter maintenance are allowed Lung tumors in a central position. Cardiac exclusion criteria: Left ventricular ejection fraction (LVEF)< 50% by echocardiography; Previous history of MI or ischemic heart disease EKG findings suggestive of current or previous ischemic heart disease, including left bundle branch block Prior treatment with chemotherapy agents known to potentially cause cardiotoxicity Class III or IV heart failure as defined by the New York Heart(NYHA) functional classification Congenital or acquired long QT syndrome Uncontrolled hypertension Current or past history of clinically significant arrhythmias QTc prolongation HO Symptomatic PVD (Venous or arterial) Seizure disease requiring current anticonvulsant treatment HO previous CVA or TIA HO inflammatory bowel disease (active or past) or active PUD HO previous, whole abdomen radiation therapy or more than Grade 1 residual toxicity from previous radiation therapy. History of autoimmune disease or vascular disease (venous or arterial)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABI-011<br> | Drug: ABI-011<br>* ABI-011<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT's and MTD Safety and Toxicity profile | Evaluate PK and PD of ABI-011. Preliminary assessment of tumor response. | During Cycle 1, treatment period, End of Study and Follow-Up, approximately up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and toxicity profile of repeated dosing of ABI-011 | Number of subjects with Adverse Events; laboratory assessments, ECG assessments, opthalmologic assessments | End of study and follow up, approximately up to 2 years | 
| Evaluate plasma PK of ABI-011 on this schedule |  | End of Study and follow-up, Up to two years | 
| Assess biological activity and PD of ABI-011 |  | End of study and follow-up, approximately 2 years | 
| Make preliminary assessment of tumor response |  | End of study and follow-up, approximately 2 years | 
| Assess biological activity/exploratory during treatment C1, C2, EOS |  | End of Study and follow-up, aproximately two years |