Bevacizumab And Erlotinib In Treating Patients With Metastatic Pancreatic Cancer That Did Not Respond To Previous Treatment With Gemcitabine

Study Overview

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

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.

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.

Pancreatic Cancer

BIOLOGICAL: bevacizumab
DRUG: erlotinib hydrochloride
OTHER: laboratory biomarker analysis

054511
UCSF-054511
UCSF-H12191-28233-01

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2006-08-16	Results First Submitted 2013-09-18	Last Update Submitted that met QC Criteria 2017-12-19
First Submitted that Met QC Criteria 2006-08-16	Results First Submitted that Met QC Criteria 2013-09-18	Last Update Posted (ACTUAL) 2018-01-19
First Posted (ACTUAL) 2006-08-17	Results First Posted 2013-11-25	Last Verified 2017-12

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Bevacizumab Plus Erlotinib Hydrochloride A treatment cycle is 21 days: bevacizumab 15 mg/kg as a 60-90 min infusion once every 21 days, with erlotinib hydrochloride 150 mg by mouth daily	BIOLOGICAL: bevacizumab DRUG: erlotinib hydrochloride OTHER: laboratory biomarker analysis

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Bevacizumab Plus Erlotinib Hydrochloride

A treatment cycle is 21 days: bevacizumab 15 mg/kg as a 60-90 min infusion once every 21 days, with erlotinib hydrochloride 150 mg by mouth daily

BIOLOGICAL: bevacizumab

DRUG: erlotinib hydrochloride

OTHER: laboratory biomarker analysis

Primary Outcome Measures	Measure Description	Time Frame
Overall Survival Rate at 6 Months	Number of participants alive at 6 months	6 months
Safety and Toxicity	Treatment associated toxicities. Adverse event assessments were performed on day 1 of each treatment cycle and at the end of treatment; the longest duration of treatment was 7 cycles (x 3 weeks)	21 weeks

Secondary Outcome Measures	Measure Description	Time Frame
Objective Response as Measured by RECIST Criteria	Participants experiencing objecting response, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	21 weeks
Time to Tumor Progression	Time to tumor progression (TTP) was defined as the time from initial therapy to the first objective documentation of tumor progression (for patients with measurable disease) or to the data of death, if death was ascribed to progression of disease.	from initial therapy to the first objective documentation of tumor progression
Proportion of Patients With ≥ 25% Decline in Serum CA19-9 Biomarker		21 weeks

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_CHAIR: Andrew Ko, MD, University of California, San Francisco

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Ko AH, Venook AP, Bergsland EK, Kelley RK, Korn WM, Dito E, Schillinger B, Scott J, Hwang J, Tempero MA. A phase II study of bevacizumab plus erlotinib for gemcitabine-refractory metastatic pancreatic cancer. Cancer Chemother Pharmacol. 2010 Nov;66(6):1051-7. doi: 10.1007/s00280-010-1257-5. Epub 2010 Feb 4.
Ko AH, Dito E, Schillinger B, et al.: A phase II study of bevacizumab (BEV) and erlotinib (ERL) in patients with gemcitabine (GEM)-refractory metastatic adenocarcinoma of the pancreas (PanCa). [Abstract] American Society of Clinical Oncology 2007 Gastrointestinal Cancers Symposium, 19 -21 January 2007, Orlando, Florida A-187, 2007.

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