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

Alternate Title

Epothilone D in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer That Has Not Responded to Platinum-Based Chemotherapy

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 18 and over NCI, Pharmaceutical / Industry MSKCC-03134 ROCHE-N017352, KOS-201, NCT00081107

Objectives

Primary

1. Determine the antitumor activity of epothilone D, in terms of confirmed objective response rate, in patients with stage IIIB or IV non-small cell lung cancer who failed prior initial platinum-containing chemotherapy.

Secondary

1. Determine the safety of this drug in these patients.
2. Determine the response duration in patients who achieve complete response or partial response, time to tumor progression, and survival in patients treated with this drug.
3. Compare the power associated with the estimated treatment effect of this drug in these patients vs standard treatment.
4. Correlate efficacy and safety with plasma concentrations of this drug and its major metabolites in these patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
  • Stage IIIB* or IV disease

   [Note: *Due to malignant pleural effusion or supraclavicular lymph node involvement only]




• Previously treated with maximally feasible surgical resection and/or radiotherapy for initial disease



• Failed 1 prior platinum-containing chemotherapy regimen for advanced or metastatic disease due to disease progression or treatment toxicity



• At least 1 site of unidimensionally measurable disease by physical exam or radiography



• No known CNS metastases or leptomeningeal metastases requiring corticosteroids

Prior/Concurrent Therapy:

Biologic therapy

• No concurrent granulocyte-macrophage colony-stimulating factor (sargramostim [GM-CSF])
• No concurrent routine prophylactic granulocyte colony-stimulating factor (filgrastim [G-CSF])

Chemotherapy

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy and recovered

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered

Surgery

• See Disease Characteristics
• At least 3 weeks since prior surgery and recovered

Other

• Prior adjuvant or neoadjuvant therapy allowed
• Prior radiosensitizers allowed
• At least 2 weeks since prior gefitinib
• More than 3 weeks since prior investigational agents (therapeutic or diagnostic)
• No other concurrent investigational agents
• No other concurrent anticancer treatment

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Hemoglobin ≥ 8 g/dL
• Platelet count ≥ 75,000/mm³

Hepatic

• AST ≤ 2.5 times upper limit of normal (ULN) (5 times ULN for patients with hepatic metastases)
• Alkaline phosphatase ≤ 5 times ULN
• Bilirubin ≤ 1.8 mg/dL

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• No New York Heart Association class III or IV congestive heart failure
• No personal or family history of congenital long QT syndrome
• No QTc interval > 450 msec (males) or > 470 msec (females) by ECG

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No preexisting neuropathy ≥ grade 2
• No other malignancy within the past 5 years except for the following:
  • Cured basal cell skin cancer
  • Carcinoma in situ of the cervix or urinary bladder
  • Stage T1 or T2 prostate cancer with prostate-specific antigen < 2 ng/mL
• No hypersensitivity reaction ≥ grade 3 to prior Cremophor-containing therapy
• No infection requiring parenteral or oral anti-infective therapy
• No weight loss of ≥ 10% within the past 3 months
• No altered mental status or psychiatric illness that would preclude giving informed consent
• No other medical condition that would preclude study participation

Expected Enrollment

A total of 33-85 patients will be accrued for this study.

Outline

This is a multicenter, open-label study.

Patients receive epothilone D IV over 90 minutes on days 1, 8, and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Naiyer Rizvi, MD, Principal investigator		Ph: 212-639-3204; 800-525-2225

Registry Information
Official Title		A Phase II Study of KOS-862, Administered Intravenously Weekly for 3 Weeks Every 4 Weeks, in Patients with Non-Small Cell Lung Cancer Who Have Progressed Following Initial Therapy for Advanced or Metastatic Disease
Trial Start Date		2003-12-30
Registered in ClinicalTrials.gov		NCT00081107
Date Submitted to PDQ		2004-02-23
Information Last Verified		2005-04-06
NCI Grant/Contract Number		P30-CA08748