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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 2

Conditions: Lung Cancer

Treatments: Drug: epothilone D

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00081107

ROCHE-N017352

03-134

CDR0000358910 (Registry Identifier)

KOS-201

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as epothilone D, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well epothilone D works in treating patients with stage IIIB or stage IV non-small cell lung cancer that has not responded to platinum-based chemotherapy.

Full description

OBJECTIVES:

Primary

• 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

• Determine the safety of this drug in these patients.
• 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.
• Compare the power associated with the estimated treatment effect of this drug in these patients vs standard treatment.
• Correlate efficacy and safety with plasma concentrations of this drug and its major metabolites in these patients.

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.

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

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Hemoglobin ≥ 8 g/dL
• Platelet count ≥ 75,000/mm^3

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

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