Bevacizumab and Erlotinib in Treating Patients With Metastatic Pancreatic Cancer That Did Not Respond to Previous Treatment With Gemcitabine

University of California San Francisco (UCSF)

Status and phase

Completed

Phase 2

Conditions

Pancreatic Cancer

Treatments

Other: laboratory biomarker analysis

Biological: bevacizumab

Drug: erlotinib hydrochloride

Study type

Interventional

Funder types

Other

Identifiers

NCT00365144

UCSF-H12191-28233-01

054511

UCSF-054511

Details and patient eligibility

About

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of pancreatic cancer by blocking blood flow to the tumor. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving bevacizumab together with erlotinib may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with erlotinib works in treating patients with metastatic pancreatic cancer that did not respond to previous treatment with gemcitabine.

Full description

OBJECTIVES:

Primary

Evaluate the 6-month overall survival rate in patients with gemcitabine hydrochloride-refractory metastatic pancreatic cancer treated with bevacizumab and erlotinib hydrochloride.
Determine the safety and toxicity of this regimen in these patients.

Secondary

Evaluate the objective response rate in these patients.
Evaluate time to tumor progression in these patients.
Determine the efficacy of this regimen, in terms of the proportion of patients with ≥ 50% decline in carbohydrate antigen 19-9, also called cancer antigen 19-9 (CA19-9) biomarker, in these patients.
Obtain sequential measurements of circulating tumor cells (micrometastases) and endothelial cells in serum and correlate these variables with clinical outcomes (in patients enrolled in UCSF site only).

OUTLINE: This is an open-label, nonrandomized, multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral erlotinib hydrochloride once daily on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection at baseline and periodically during study for biomarker/laboratory analysis, including the CA19-9 biomarker. Circulating tumor micrometastases and endothelial cells are also measured in patients enrolled in University of California San Francisco (UCSF) site.

After completion of study treatment, patients are followed at 30 days and at 6 months.

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

Enrollment

36 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed adenocarcinoma of the pancreas
Documented extrapancreatic metastases
- Radiographically measurable disease not required
Gemcitabine hydrochloride-refractory disease
- Has undergone 1-3 prior therapies for locally advanced or metastatic disease with ≥ 1 regimen containing gemcitabine hydrochloride (alone or in combination with other agents)
  - Treatment given in the adjuvant setting (radiotherapy and/or chemotherapy, given either concurrently or systemically) does not count as prior therapy as long as progressive disease occurs > 6 months after completion of treatment
No central nervous system (CNS) or brain metastases

PATIENT CHARACTERISTICS:

Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
International Normalized Ratio (INR) ≤ 1.5 (except in patients receiving full-dose warfarin)
Bilirubin ≤ 2.0 mg/dL
Creatinine ≤ 2.0 mg/dL
AST or ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if documented liver metastases)
Hemoglobin ≥ 9 g/dL (transfusion or epoetin alfa allowed)
No contact lense use during and for 14 days after completion of study treatment
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
No history of other disease, metabolic dysfunction, or physical examination or clinical laboratory finding that contraindicates use of an investigational drug or precludes study compliance
No history of serious systemic disease, including any of the following:
- Myocardial infarction within the past 6 months
- Stroke within the past 6 months
- Uncontrolled hypertension (i.e., blood pressure > 150/100 mm Hg on medication)
- Unstable angina
- New York Heart Association class II-IV congestive heart failure
- Unstable symptomatic arrhythmia requiring medication
  - Chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) allowed
- Peripheral vascular disease ≥ grade 2
No significant traumatic injury within the past 28 days
No proteinuria (defined as urine protein:creatinine ratio ≥ 1.0 at screening)
No clinically significant impairment of renal function
No serious, nonhealing wound, ulcer, or bone fracture
No evidence of bleeding diathesis or coagulopathy
No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months

PRIOR CONCURRENT THERAPY:

More than 28 days since prior major surgery or open biopsy
More than 7 days since prior fine-needle aspiration or core biopsy
No prior antiangiogenesis agent (e.g., bevacizumab or an oral vascular endothelial growth factor receptor small molecule inhibitor) given together with an agent that disrupts epidermal growth factor receptor signaling (e.g., cetuximab or erlotinib hydrochloride) for locally advanced or metastatic pancreatic cancer
- Prior treatment with either one of the above alone allowed
More than 4 weeks since prior and no concurrent participation in another clinical trial
No other concurrent antineoplastic or antitumor agents, including chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy
No concurrent major surgery
No other concurrent investigational agents