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A PhaseI/II Study Evaluating the Safety, Tolerability, and Maximally Tolerated Dose of L-377202 Administered Once Every 3 Weeks


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Male
Hormone Refractory Prostate Cancer, Prostate Cancer

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Trial Information

A PhaseI/II Study Evaluating the Safety, Tolerability, and Maximally Tolerated Dose of L-377202 Administered Once Every 3 Weeks


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).


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.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Evaluation of the administration of L-377202 every three weeks in patients with hormone refractory prostate cancer

Outcome Time Frame:

Every 3 weeks until disease progression or unacceptable toxicity

Safety Issue:

Yes

Principal Investigator

John Rinehart, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Alabama at Birmingham (no longer employee)

Authority:

United States: Food and Drug Administration

Study ID:

F990224004

NCT ID:

NCT00987753

Start Date:

March 1999

Completion Date:

November 2001

Related Keywords:

  • Hormone Refractory Prostate Cancer
  • Prostate Cancer
  • L-377202, prostate cancer, PSA
  • Prostatic Neoplasms

Name

Location

University of Alabama at BirminghamBirmingham, Alabama  35294-3300