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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2010 by Royal Marsden NHS Foundation Trust.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Professor Cunningham's Clinical Research Fund
Hoffmann-La Roche
Information provided by:
Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00260364
First received: November 29, 2005
Last updated: January 5, 2010
Last verified: January 2010
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Royal Marsden NHS Foundation Trust:

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

Secondary Outcome Measures:
  • 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

Estimated Enrollment: 40
Study Start Date: November 2005
Estimated Study Completion Date: December 2009
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.

  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
  • 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
  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: NCT00260364

Locations
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
Investigators
Principal Investigator: David Cunningham, MD, FRCP The Royal Marsden Hospital NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Jane Lawrence, Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT00260364     History of Changes
Other Study ID Numbers: CCR2631, EudraCT No.: 2005-002715-24
Study First Received: November 29, 2005
Last Updated: January 5, 2010
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

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

ClinicalTrials.gov processed this record on November 23, 2014