Study Evaluating the Safety and Tolerability of L-377202

NCT00987753 | Completed Phase 1 DMC

• 2 other identifiers: F990224004UAB 9902
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hormone Refractory Prostate Cancer; Prostate Cancer

Keywords

L-377202, prostate cancer, PSA

Outcome Measures

Primary Outcomes (1)

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

  Every 3 weeks until disease progression or unacceptable toxicity

Secondary Outcomes (1)

• Evaluation of the radiologic and/or PSA responses to L-377202 treatment

  Every 3 weeks until disease progression or unacceptable toxicity

Study Arms (1)

infusion of L-377202

EXPERIMENTAL

Drug: L-377202

Interventions

L-377202 DRUG

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.

infusion of L-377202

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Salivary Gland Adenoma, Pleomorphic

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• 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)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Proffessor

Study Record Dates

• First Submitted: September 30, 2009
• First Posted: October 1, 2009
• Study Start: March 1, 1999
• Primary Completion: September 1, 2000
• Study Completion: November 1, 2001
• Last Updated: May 25, 2023

Record last verified: 2023-05

Locations

US (1)