Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Epothilone D in Treating Patients With Advanced Solid Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over NCI, Pharmaceutical / Industry UCLA-0106021 KOS-101, NCI-G02-2054, NCT00033501

Objectives

1. Determine the maximum tolerated dose and recommended phase II dose of epothilone D in patients with advanced solid tumors.
2. Determine the safety and dose-limiting toxicity of this drug in these patients.
3. Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.
4. Determine, preliminarily, any antitumor activity of this drug in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed primary or metastatic solid tumor that is refractory to standard therapy or for which no standard curative therapy exists
  • Including but not limited to:
    • Breast cancer
    • Ovarian cancer
    • Head and neck cancer
    • Esophageal cancer
    • Lung cancer
    • Cancer of the gastrointestinal tract
    • Sarcomas



• Measurable or evaluable disease by radiography



• No known intracranial edema, intracranial metastasis, or epidural disease

Prior/Concurrent Therapy:

Biologic therapy:

• No concurrent antibody therapy, immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or matrix metalloprotease inhibitors
• No concurrent sargramostim (GM-CSF)

Chemotherapy:

• At least 21 days since prior antineoplastic therapy (except hormonal therapy) and recovered
• No other concurrent chemotherapy

Endocrine therapy:

• See Chemotherapy
• No concurrent anticancer hormonal therapy

Radiotherapy:

• No prior external beam radiotherapy to 25% or more of bone marrow-containing skeleton
• Recovered from prior radiotherapy
• No concurrent radiotherapy

Surgery:

• Recovered from prior surgery

Other:

• No concurrent alcohol intake
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer therapy

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 75,000/mm³
• Hemoglobin at least 8.0 g/dL

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• Alkaline phosphatase no greater than 5 times upper limit of normal (ULN)
• AST/ALT no greater than 2.5 times ULN (5 times ULN if tumor involvement of the liver present)

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No New York Heart Association class III or IV heart disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Lactic dehydrogenase no greater than 5 times ULN
• No pre-existing peripheral neuropathy grade 2 or greater
• No prior hypersensitivity reaction to paclitaxel or other therapy containing
• Cremophor EL
• No dementia or altered mental status that would preclude study
• No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation

Expected Enrollment

Approximately 15-40 patients will be accrued for this study within 6-8 months.

Outline

This is a dose-escalation study.

Patients receive epothilone D IV on day 1. Treatment repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of epothilone D until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, a total of 15 patients are treated at that dose level.

Patients are followed for 30 days, every 2 months for 1 year, and then every 3 months for 2 years.

Trial Contact Information

Trial Lead Organizations

Jonsson Comprehensive Cancer Center at UCLA

Lee Rosen, MD, Protocol chair(Contact information may not be current)		Ph: 310-825-5268; 888-798-0719

Registry Information
Official Title		A Phase I Dose Escalation Trial To Evaluate The Safety, Pharmacokinetics, And Pharmacodynamics Of Epothilone D In Patients With Advanced Solid Tumors
Trial Start Date		2002-09-26
Registered in ClinicalTrials.gov		NCT00033501
Date Submitted to PDQ		2002-02-20
Information Last Verified		2003-01-10
NCI Grant/Contract Number		P30-CA16042