Clinical trial NCT00519831: Ph II of Vinflunine and Cetuximab in Second Line Treatment of NSCLC
Official title: Phase II Study of Vinflunine and Cetuximab in the Second Line Treatment of Stage IIIB/IV Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer
recurrent non-small cell lung cancer
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2007-08-23
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as vinflunine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and help kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Giving vinflunine together with cetuximab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving vinflunine together with cetuximab works as second-line therapy in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Detailed description: OBJECTIVES:

Primary

* Estimate the objective response rate in patients receiving vinflunine and cetuximab as second-line therapy for stage IIIB or IV non-small cell lung cancer.

Secondary

* Determine the progression-free survival of patients treated with this regimen.
* Determine the safety of this regimen in these patients.
* Determine the overall survival of patients treated with this regimen.
* Determine the duration of overall response in these patients.

OUTLINE: This is a multicenter study.

Patients receive vinflunine IV over 15-20 minutes on day 1 and cetuximab IV over 60-120 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease may receive additional courses beyond 4 courses at the discretion of the principal investigator.

After completion of study therapy, patients are followed periodically for 6 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) meeting 1 of the following criteria:

  * Unresectable stage IIIB disease with pleural effusion or pericardial effusion
  * Stage IIIB disease that was treated with chemotherapy alone as first-line therapy
  * Stage IV disease
* Must have documented progression of disease after receiving one cytotoxic chemotherapy regimen for metastatic disease
* At least one lesion that is bidimensionally measurable by CT scan or MRI

  * Must have evaluable disease outside the radiation field

    * New lesions that develop within the radiation field are allowed
* Measurable disease status as defined by RECIST criteria
* Brain metastases allowed provided they have been previously treated and are controlled

PATIENT CHARACTERISTICS:

Inclusion criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Absolute neutrophil count (ANC) \> 1,000/mm³
* Hemoglobin \> 8.0 g/dL
* Platelet count \> 75,000/mm³
* Creatinine \< 2.0 times upper limit of normal (ULN)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 5 times ULN
* Total bilirubin \< 2.5 times ULN
* Prior malignancy allowed provided the patient's life expectancy is best defined by the diagnosis of NSCLC
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for up to 4 weeks after completion of study therapy

Exclusion criteria:

* Peripheral neuropathy ≥ 2
* Severe allergic reaction to prior vinca alkaloid treatment
* Active or uncontrolled infection
* Significant history of uncontrolled cardiac disease, including any of the following:

  * Uncontrolled hypertension
  * Unstable angina
  * Myocardial infarction within the past 6 months
  * Uncontrolled congestive heart failure
  * Cardiomyopathy with decreased ejection fraction
* Severe reaction to prior monoclonal antibody therapy

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

* See Disease Characteristics
* Prior oral tyrosine kinase inhibitor therapy (e.g. gefitinib or erlotinib) allowed

  * Not considered cytotoxic therapy for study eligibility purposes if given alone as first-line therapy
* At least 1 week since prior radiotherapy
* At least 21 days since prior and no other concurrent chemotherapy
* Prior adjuvant therapy allowed provided patient received one cytotoxic chemotherapy regimen as treatment for metastatic disease
* Prior bevacizumab allowed

Exclusion criteria:

* Two or more cytotoxic chemotherapy regimens as treatment for metastatic disease
* Prior therapy with monoclonal antibody directed at the epidermal growth factor receptor (EGFR) pathway
* Prior therapy with a vinca alkaloid in the metastatic setting
* Concurrent bevacizumab
* Other concurrent investigational agent(s)
* Concurrent colony-stimulating factors as primary prophylaxis for the prevention of febrile neutropenia
* Concurrent CYP3A4 inhibitor(s)

Primary outcomes:
measure: Overall Tumor Response Rate as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Sum of Partial Responses (PR) and Complete Responses (CR).
timeFrame: Baseline, after cycle 2, within 2 weeks of completing cycle 4
Secondary outcomes:
measure: Duration of Response
timeFrame: After cycle 4
measure: Overall Survival
timeFrame: Every 30 days
measure: Progression-free Survival
timeFrame: after cycle 2, within 2 weeks of completing cycle 4
Other outcomes:
Locations:
city: Burlington
country: United States
facility: Alamance Oncology/Hematology Associates, LLP
state: North Carolina
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Thomas E. Stinchcombe, MD
role: PRINCIPAL_INVESTIGATOR
References: