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

Alternate Title

Volociximab and Erlotinib in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over NCI, Pharmaceutical / Industry UCLA-0504066-01 PDL-M200-1206, NCT00278187

Objectives

Primary

1. Evaluate the response rate in patients with locally advanced (stage IIIB) or metastatic (stage IV) non-small cell lung cancer treated with volociximab and erlotinib hydrochloride.

Secondary

1. Evaluate the time to disease progression and duration of response in patients treated with this regimen.
2. Evaluate the safety of this drug regimen in these patients.
3. Evaluate the pharmacokinetics this regimen in these patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed locally advanced (stage IIIB) or metastatic (stage IV) non-small cell lung cancer (NSCLC)



• Failed ≥ 1 prior chemotherapy regimen OR refused first-line therapy



• Measurable disease



• No active and untreated CNS tumor or metastasis
  • Previously treated CNS tumor(s) allowed if CT scan or MRI shows clear-cut response or resolution of the original lesion(s)

Prior/Concurrent Therapy:

• See Disease Characteristics
• Prior immunotherapy, including monoclonal antibodies, or vaccine therapy allowed
• No systemic biologic, immunotherapy, or radiation therapy within the past 4 weeks
  • Local radiotherapy to a single site of bone metastasis within the past 2 weeks allowed provided patient has recovered from any side effects
• No prior volociximab, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, or inhibitors of α5β1 integrin (antibodies or small molecules)
• No known hypersensitivity to murine proteins or chimeric antibodies or other components of study drugs
• No other investigational drug within the past 4 weeks or 5 half-lives (whichever is longer)
• No monoclonal antibody therapy within the past 4 weeks or 5 half-lives (whichever is longer)
• No major surgery (e.g., thoracotomy) within 4 weeks prior to study entry
• No minor surgery (e.g., central venous line placement) within 1 week prior to study entry
• No sargramostim (GM-CSF) or filgrastim (G-CSF) within the past 7 days
• No prior bone marrow or stem cell transplantation
• No concurrent chronic medications that would interfere with study drug assessment including, but not limited to:
  • High-dose glucocorticoids (prednisone ≥ 20 mg/day or equivalent)
  • Chronic nonsteroidal anti-inflammatory drugs (NSAIDs)
    • Infrequent or as occasion requires use of NSAIDs allowed
• No concurrent high-dose aspirin (> 81 mg/day), high-dose warfarin, or heparin
  • Aspirin ≤ 81 mg/day, low-dose warfarin (1 mg/day), or low-dose heparin for IV-catheter patency allowed
• No concurrent chemotherapy, therapeutic radiation, or anticancer hormonal therapy
• No other concurrent immunotherapy
• No other concurrent potentially antiangiogenic therapy (e.g., cyclo-oxygenase-2 inhibitors, thalidomide, or tretinoin)

Patient Characteristics:

• ECOG performance status 0-1
• Hemoglobin ≥ 9.0 g/dL
• WBC ≥ 2,500/mm³
• Absolute neutrophil count ≥ 1,000/mm³ (growth factor independent)
• Platelet count ≥ 100,000/mm³
• Total bilirubin ≤ 1.5 mg/dL
• AST and ALT ≤ 3 times upper limit of normal (ULN) (5 times ULN if patient has liver metastases)
• Alkaline phosphatase ≤ 5 times ULN
• Serum creatinine ≤ 2.0 mg/dL
• PT/PTT normal
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective (double barrier or abstinence) contraception
• No uncontrolled seizure disorder or active neurological disease
• No thromboembolic events (i.e., stroke or deep vein thrombosis) within the past year
• No clinically significant medical condition that would complicate compliance with study treatment or be exacerbated by bleeding, including but not limited to:
  • Known bleeding disorders, such as coagulation defects and thrombasthenias
  • Active gastric or duodenal ulcer
  • History of gastrointestinal (GI) bleeding requiring transfusion within the past year
  • History of tumor bleeding
  • History of significant hemoptysis requiring intervention (i.e., transfusion, laser therapy, surgical treatment, or radiation) within the past year
• No known active infections requiring IV antibiotics, antivirals, or antifungals (e.g., HIV, hepatitis B, or hepatitis C infection)
• No unstable cardiac disease, including any of the following:
  • Poorly controlled angina
  • Congestive heart failure
  • Arrhythmias
  • Myocardial infarction within the past year
  • Acute ischemia by ECG
  • Untreated significant conduction abnormality
    • Bifascicular block (defined as left anterior hemiblock in the presence of right bundle branch block)
    • Second- or third-degree atrioventricular block
• No asthma or oxygen-dependent chronic pulmonary disease
• No cerebrovascular event (e.g., stroke or transient ischemic attack) within the past year
• No peripheral vascular disease requiring surgery within the past year
• No clinically significant or unstable medical condition, including, but not limited to, any of the following:
  • Diabetes mellitus requiring insulin
  • Uncontrolled hypertension
  • Uncontrolled or symptomatic orthostatic hypertension
• No serious psychiatric illness, active alcoholism, or drug addiction that may preclude study treatment
• No condition that, in the investigator's opinion, would make the patient unsuitable for study treatment

Expected Enrollment

A total of 40 patients will be accrued for this study.

Outcomes

Proportion of patients with confirmed tumor response

Time to disease progression
Duration of response
Adverse events and serious adverse events
Pharmacokinetics
Immunogenicity

Outline

This is an open-label, multicenter study.

Patients receive volociximab IV over 30 minutes once every 2 weeks and oral erlotinib hydrochloride daily for 52 weeks in the absence of unacceptable toxicity or disease progression.

After completion of study treatment, patients are followed at 3 and 6 months.

Trial Contact Information

Trial Lead Organizations

Jonsson Comprehensive Cancer Center at UCLA

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

Registry Information
Official Title		Phase II Open-Label Study of Volociximab (M200) in Combination With Erlotinib (Tarceva™) in Previously Treated Patients With Locally Advanced (Stage IIIb) or Metastatic (Stage IV) Non-Small Cell Lung Cancer
Trial Start Date		2005-07-19
Registered in ClinicalTrials.gov		NCT00278187
Date Submitted to PDQ		2005-09-14
Information Last Verified		2006-02-07
NCI Grant/Contract Number		CA16042