A Phase 1 Trial of ABI-011 in Patients With Advanced Solid Tumors or Lymphomas
Primary Purpose
Advanced Solid Tumors
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ABI-011
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Solid Tumors
Eligibility Criteria
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)
Sites / Locations
- Karmanos Cancer Center Institute
- CTRC @ The Utah Health Science Center @ San Antonio
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ABI-011
Arm Description
Outcomes
Primary Outcome Measures
DLT's and MTD Safety and Toxicity profile
Evaluate PK and PD of ABI-011. Preliminary assessment of tumor response.
Secondary Outcome Measures
Safety and toxicity profile of repeated dosing of ABI-011
Number of subjects with Adverse Events; laboratory assessments, ECG assessments, opthalmologic assessments
Evaluate plasma PK of ABI-011 on this schedule
Assess biological activity and PD of ABI-011
Make preliminary assessment of tumor response
Assess biological activity/exploratory during treatment C1, C2, EOS
Full Information
NCT ID
NCT01163071
First Posted
June 15, 2010
Last Updated
November 13, 2019
Sponsor
Celgene
Collaborators
Celgene Corporation
1. Study Identification
Unique Protocol Identification Number
NCT01163071
Brief Title
A Phase 1 Trial of ABI-011 in Patients With Advanced Solid Tumors or Lymphomas
Official Title
A Phase I Trial of ABI-011 Administered Weekly in Patients With Advanced Solid Tumors or Lymphomas
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Terminated
Study Start Date
March 1, 2011 (Actual)
Primary Completion Date
September 23, 2011 (Actual)
Study Completion Date
September 23, 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
Collaborators
Celgene Corporation
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
Dose limiting toxicities (DLT), maximum tolerated dose (MTD)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ABI-011
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
ABI-011
Intervention Description
ABI-011
Primary Outcome Measure Information:
Title
DLT's and MTD Safety and Toxicity profile
Description
Evaluate PK and PD of ABI-011. Preliminary assessment of tumor response.
Time Frame
During Cycle 1, treatment period, End of Study and Follow-Up, approximately up to 2 years
Secondary Outcome Measure Information:
Title
Safety and toxicity profile of repeated dosing of ABI-011
Description
Number of subjects with Adverse Events; laboratory assessments, ECG assessments, opthalmologic assessments
Time Frame
End of study and follow up, approximately up to 2 years
Title
Evaluate plasma PK of ABI-011 on this schedule
Time Frame
End of Study and follow-up, Up to two years
Title
Assess biological activity and PD of ABI-011
Time Frame
End of study and follow-up, approximately 2 years
Title
Make preliminary assessment of tumor response
Time Frame
End of study and follow-up, approximately 2 years
Title
Assess biological activity/exploratory during treatment C1, C2, EOS
Time Frame
End of Study and follow-up, aproximately two years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patricia M LoRusso, DO
Organizational Affiliation
Karmanos Cancer Institute Hudson-Webber Cancer Research Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
John Sarantopoulos, MD
Organizational Affiliation
Cancer Therapy Research Center at the University Health Sciences Center at San Antonio
Official's Role
Principal Investigator
Facility Information:
Facility Name
Karmanos Cancer Center Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
CTRC @ The Utah Health Science Center @ San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Phase 1 Trial of ABI-011 in Patients With Advanced Solid Tumors or Lymphomas
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