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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00365144
First received: August 16, 2006
Last updated: November 22, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Pancreatic Cancer
Biological: bevacizumab
Drug: erlotinib hydrochloride
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Bevacizumab Plus Erlotinib for Patients With Metastatic Gemcitabine-Refractory Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Overall Survival Rate at 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Number of participants alive at 6 months

  • Safety and Toxicity [ Time Frame: 21 weeks ] [ Designated as safety issue: Yes ]
    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)


Secondary Outcome Measures:
  • Objective Response as Measured by RECIST Criteria [ Time Frame: 21 weeks ] [ Designated as safety issue: No ]
    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.

  • Time to Tumor Progression [ Time Frame: 132 days ] [ Designated as safety issue: No ]
    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. Patients initially without measurable disease were included in the analysis based either on the appearance of new measurable lesions or on strongly suggestive radiographic evidence of progression of non-measurable disease). Participants were followed for tumor progression; the longest duration without progression was 132 days.

  • Proportion of Patients With ≥ 25% Decline in Serum CA19-9 Biomarker [ Time Frame: 21 weeks ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: February 2006
Study Completion Date: March 2010
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Bevacizumab Plus Erlotinib Biological: bevacizumab Drug: erlotinib hydrochloride Other: laboratory biomarker analysis

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00365144

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
Investigators
Study Chair: Andrew Ko, MD University of California, San Francisco
  More Information

Additional Information:
Publications:
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.

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00365144     History of Changes
Other Study ID Numbers: CDR0000491225, UCSF-054511, UCSF-H12191-28233-01
Study First Received: August 16, 2006
Results First Received: September 18, 2013
Last Updated: November 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
stage IV pancreatic cancer
adenocarcinoma of the pancreas
recurrent pancreatic cancer

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Bevacizumab
Gemcitabine
Erlotinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Radiation-Sensitizing Agents
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014