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

October 13, 2016 updated by: Royal Marsden NHS Foundation Trust

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

44

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

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

Study Locations

  • United Kingdom
    • London
      • London and Surrey, London, United Kingdom, SM2 5PT
        • The Royal Marsden Foundation Hospital NHS Trust

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Eastern Cooperative Oncology Group (ECOG) 0-2

Life expectancy:

  • Greater than 3 months

Hematopoietic:

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

Hepatic:

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

Renal:

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

Cardiovascular:

  • 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

OTHER:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Part A (Phase I): Dose-limiting Toxicity (DLT)
Part B (Phase II): Overall response rate (complete response and partial response)

Secondary Outcome Measures

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

Collaborators and Investigators

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

Sponsor

Royal Marsden NHS Foundation Trust

Collaborators

Hoffmann-La Roche
Professor Cunningham's Clinical Research Fund

Investigators

  • Principal Investigator: David Cunningham, MD, FRCP, The Royal Marsden Hospital NHS Foundation Trust

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 Major Dates

Study Start

November 1, 2005

Primary Completion (Actual)

August 1, 2011

Study Completion (Actual)

August 1, 2011

Study Registration Dates

First Submitted

November 29, 2005

First Submitted That Met QC Criteria

November 29, 2005

First Posted (Estimate)

December 1, 2005

Study Record Updates

Last Update Posted (Estimate)

October 14, 2016

Last Update Submitted That Met QC Criteria

October 13, 2016

Last Verified

January 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCR2631
  • EudraCT No.: 2005-002715-24

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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