Combining Erlotinib Plus Bevacizumab and Gemcitabine Plus Capecitabine to Treat Advanced Pancreatic Cancer (TARGET)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00260364
Recruitment Status : Completed
First Posted : December 1, 2005
Last Update Posted : October 14, 2016
Professor Cunningham's Clinical Research Fund
Hoffmann-La Roche
Information provided by (Responsible Party):
Royal Marsden NHS Foundation Trust

Brief Summary:
Pancreatic cancer is an aggressive, largely chemo-resistant disease with a poor prognosis. EGFR and VEGF are both overexpressed in pancreatic cancers and thought to contribute to tumour development and progression. The combination of gemcitabine and capecitabine has recently been shown to be effective in advanced pancreatic cancer. The combination of gemcitabine plus erlotinib has also been shown to be effective in advanced pancreatic cancer. The aim of this study is to assess whether combining a chemotherapy doublet (gemcitabine plus capecitabine) and a biologic doublet (erlotinib plus bevacizumab) is a safe and effective way to treat advanced pancreatic cancer by targeting multiple tumour stimulating mechanisms simultaneously.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: Gemcitabine 1000 mg/m2 iv days 1, 8, 15 of a 28 day cycle Drug: Capecitabine orally days 1 -21 Drug: Erlotinib 100 mg orally days 1-28 Drug: Bevacizumab 5 mg/kg intravenously every 2 weeks Phase 1 Phase 2

Detailed Description:

To establish the safety and efficacy of a combination of four drugs (capecitabine, gemcitabine, erlotinib and bevacizumab) in the treatment of patients with locally advanced or metastatic pancreatic cancer. The study will be divided into two parts:

Part A (Phase I ): Is to establish the optimal dose of capecitabine for combination with gemcitabine, bevacizumab and erlotinib. This part of the study is necessary in order to characterise any increased side effects that may occur as a result of this combination of drugs. The dose of capecitabine will be increased in cohorts containing 3 to 6 patients(according to standard dose escalation study design) whilst side effects are closely monitored. The doses of the other three drugs will remain fixed during this period:

  • Gemcitabine: 1000 mg/m2 Days 1, 8, 15
  • Bevacizumab: 5 mg/kg every two weeks iv
  • Erlotinib: 100 mg/day orally

Maximum tolerated dose is the dose at which 2 out of a cohort of three to six patients experience dose-limiting toxicity within the first cycle (28 days) of treatment. The recommended dose for further evaluation will be one dose level below this.

Part B (Phase II): Once a recommended dose of capecitabine has been chosen, this will be used for the remainder of the trial to further characterise the efficacy and safety of the drug combination in this group of patients.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I-II Dose Finding and Early Efficacy Study of Combination Therapy With Erlotinib (Tarceva), Gemcitabine, Bevacizumab (Avastin), and Capecitabine in Advanced Pancreatic Cancer
Study Start Date : November 2005
Actual Primary Completion Date : August 2011
Actual Study Completion Date : August 2011

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Part A (Phase I): Dose-limiting Toxicity (DLT)
  2. Part B (Phase II): Overall response rate (complete response and partial response)

Secondary Outcome Measures :
  1. The secondary efficacy objectives of the trial are: One year survival and median overall survival
  2. Progression free survival, Disease control rate.
  3. The secondary safety objectives are: Toxicity,Quality of life
  4. and Assessment of pain

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically or cytologically confirmed adenocarcinoma of the pancreas
  • Locally advanced or metastatic disease
  • Not amenable to curative resection
  • No invasion of adjacent organs (e.g., duodenum or stomach) by CT scan
  • Unidimensionally measurable disease as assessed by CT in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.
  • No evidence of brain metastasis



  • 18 and over

Performance status:

  • Eastern Cooperative Oncology Group (ECOG) 0-2

Life expectancy:

  • Greater than 3 months


  • Granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3


  • Bilirubin ≤ upper limit of normal
  • Serum albumin > 26 g/litre


  • Creatinine ≤ 180 micromoles/litre OR
  • Creatinine clearance ≥ 50 mL/min


  • No clinically significant cardiovascular disease
  • No uncontrolled hypertension (i.e., blood pressure > 150/90 mm Hg on medication)
  • No arterial thromboembolic event within the past 6 months, including any of the following:

    • Myocardial infarction
    • Unstable angina pectoris
    • Cerebrovascular accident
    • Transient ischemic attack
  • No New York Heart Association grade II-IV congestive heart failure
  • No serious cardiac arrhythmia requiring medication


  • Not pregnant or breast feeding
  • Fertile patients must use effective contraception during study participation
  • No serious or non-healing wound, ulcer, or bone fracture
  • No infection requiring parenteral antibiotics
  • No major bleeding diathesis or coagulopathy
  • No significant traumatic injury within the past 28 days
  • No surgery within the last 28 days or anticipation for the need for major surgery during the course of study treatment
  • No other active malignancy except non-melanoma skin cancer and cervical cancer in-situ
  • No history of known dihydropyrimidine dehydrogenase (DPD) deficiency
  • No lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, or inability to take oral medication


  • No previous chemotherapy, radiotherapy or other investigational drug treatment for metastatic disease (including VEGF or EGFR antagonists)
  • No previous preoperative or adjuvant chemotherapy, radiotherapy or other investigational drug treatment.
  • No full dose anti-coagulation (i.e. warfarin or full dose low molecular weight heparin) prior to starting study treatment.
  • No ongoing treatment with aspirin (>325 mg/day) or other medications known to predispose to gastrointestinal ulceration

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00260364

United Kingdom
The Royal Marsden Foundation Hospital NHS Trust
London and Surrey, London, United Kingdom, SM2 5PT
Sponsors and Collaborators
Royal Marsden NHS Foundation Trust
Professor Cunningham's Clinical Research Fund
Hoffmann-La Roche
Principal Investigator: David Cunningham, MD, FRCP The Royal Marsden Hospital NHS Foundation Trust

Responsible Party: Royal Marsden NHS Foundation Trust Identifier: NCT00260364     History of Changes
Other Study ID Numbers: CCR2631
EudraCT No.: 2005-002715-24
First Posted: December 1, 2005    Key Record Dates
Last Update Posted: October 14, 2016
Last Verified: January 2010

Keywords provided by Royal Marsden NHS Foundation Trust:
Recurrent carcinoma of the pancreas
Adenocarcinoma of the pancreas
Stage II carcinoma of the pancreas
Stage III carcinoma of the pancreas
Stage IVA carcinoma of the pancreas
Stage IVB carcinoma of the pancreas

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