- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00987753
Study Evaluating the Safety and Tolerability of L-377202
May 24, 2023 updated by: Michael James Bertram, University of Alabama at Birmingham
A PhaseI/II Study Evaluating the Safety, Tolerability, and Maximally Tolerated Dose of L-377202 Administered Once Every 3 Weeks
The primary purpose of this study is to (1) determine the maximally tolerated dose (MTD) of L-377202 administered once every 3 weeks, (2) evaluate the safety and tolerability of L-377202 including the dose-limiting adverse effects of treatment with L-377202, and (3) assess the pharmacokinetics of various doses of L-377202 and the plasma profile of liberated doxorubicin and leu-doxorubicin.
Study Overview
Status
Completed
Intervention / Treatment
Detailed Description
This is an open, nonrandomized, rising-dose study in patients with hormone refractory prostate cancer.
Patients will be treated with L-377202 once every three weeks.
Plasma concentrations of L-377202, liberated doxorubicin, and leu-doxorubicin will be obtained at defined time intervals throughout the study.
At least 1 patient will be treated at each dose level until there is evidence of greater than or equal to Grade 2 drug-related toxicity.
Each patient will be treated at only 1 dose level, although multiple cycles may be administered until signs of disease progression or unacceptable toxicity are evident.
Doses will be doubled for each subsequent cohort of patients until evidence of greater than or equal to Grade 2 drug-related toxicity.
Upon documentation of greater than or equal to Grade 2 drug-related toxicity, subsequent dose escalations will proceed along the modified Fibonacci scale and enroll at least 3 patients per dose level until 1 patient experiences dose-limiting toxicity (DLT).
Study Type
Interventional
Enrollment (Actual)
13
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Alabama
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Birmingham, Alabama, United States, 35294
- University of Alabama at Birmingham
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Patient is at least an 18-year-old male and has histologically documented, progressive carcinoma of the prostate which is refractory to hormonal manipulation. Progressive disease may be documented by new lesions on bone scan, increase in radiologically measurable disease, or an increase in PSA (at least 50% increase from nadir confirmed twice and measured at least 2 weeks apart.)
- An appropriate interval of time has passed since alteration of any hormonal therapy (e.g., 4 weeks for steroids, LHRH agonists, flutamide or megestrol acetate and 6 weeks for nilutamide and bicalutamide).
- Patient has a serum PSA of 20 ng/mL or higher.
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Patients has a life expectancy of >3 months.
- Patient understands and agrees to participate in the study by providing written informed consent.
Exclusion Criteria:
- Patient is mentally or legally incapacitated at the time of the study or has a history (less than 5 years prior to entry) of drug or alcohol abuse or is currently a user (including "recreational use") of any illicit drugs.
- Patient has known HIV or a known HIV-related malignancy.
- Patient has participated in another study (including FDA approved drugs for a non-FDA approved indication) of an investigational agent within the last 4 weeks.
- Patient requires treatment or is anticipated to require treatment with Cyclosporine, Phenobarbital, phenytoin, or streptozocin.
- Patient has received tumor directed immunologic therapy, radiation therapy, surgery, or chemotherapy within 4 weeks of the study. However, patients who are receiving thyroid replacement therapy may be included. For mitomycin or nitrosourea, there must be a 6-week treatment free interval.
- Patient has received strontium treatment within 12 weeks prior to treatment.
- Patient is anticipated to require immunologic therapy, radiation therapy, surgery, or chemotherapy during the study.
- Patient has received high-dose chemotherapy with stem cell rescue.
- Patient has a history of significant cardiac dysrhythmias (Grade 3 or higher excluding atrial fibrillation).
- Patient has recently had (within 6 months) a myocardial infarction, unstable angina, or congestive heart failure.
- Patient has an abnormal PT (INR) or a PTT (>1.2 times normal). Low-dose warfarin (1 to 2 mg P.O. q.d.) or heparin (the equivalent of 5000 IU SQ b.i.d.) administered to maintain catheter patency is acceptable. Patients administered higher doses of anticoagulants may be considered on an individual basis pending discussion between the clinical monitor and investigator. Such patients will require more intensive monitoring of PT (INR) and aPTT (at least every other day).
- Patient has an absolute neutrophil count <1500/mm3 or platelet count <100,000/mm3 or hemoglobin <9 gm/dL, bilirubin >1.5 times normal or ALT or AST >2.5 times normal or creatinine >1.5 times normal.
- Patient has an active infection.
- Patient has an active (edema, progressive disease, or clinical neurologic symptoms) metastatic CNS lesion.
- Patient has received the equivalent of >180 mg/m2 of doxorubicin or >40 mg/m2 mitoxantrone.
- Patient has left ventricular ejection fraction (LVEF) <45%.
- Patient has received radiation to >25% of his total bone marrow.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: infusion of L-377202
|
For each cycle, L-377202 will be administered as a 30-minute infusion every 3 weeks.
The starting dose will be 20 mg/m2/week.
Doses will be doubled until a patient experiences a greater than or equal to Grade 2 toxicity.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Evaluation of the administration of L-377202 every three weeks in patients with hormone refractory prostate cancer
Time Frame: Every 3 weeks until disease progression or unacceptable toxicity
|
Every 3 weeks until disease progression or unacceptable toxicity
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Evaluation of the radiologic and/or PSA responses to L-377202 treatment
Time Frame: Every 3 weeks until disease progression or unacceptable toxicity
|
Every 3 weeks until disease progression or unacceptable toxicity
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: John Rinehart, M.D., University of Alabama at Birmingham (no longer employee)
- Principal Investigator: Scot Ebbinghaus, M.D., University of Alabama at Birmingham (no longer employee)
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 1999
Primary Completion (Actual)
September 1, 2000
Study Completion (Actual)
November 1, 2001
Study Registration Dates
First Submitted
September 30, 2009
First Submitted That Met QC Criteria
September 30, 2009
First Posted (Estimated)
October 1, 2009
Study Record Updates
Last Update Posted (Actual)
May 25, 2023
Last Update Submitted That Met QC Criteria
May 24, 2023
Last Verified
May 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- F990224004
- UAB 9902
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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