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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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Pancreatic Cancer

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Trial Information

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

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.

Inclusion Criteria


- 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Part A (Phase I): Dose-limiting Toxicity (DLT)

Principal Investigator

David Cunningham, MD, FRCP

Investigator Role:

Principal Investigator

Investigator Affiliation:

The Royal Marsden Hospital NHS Foundation Trust


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

November 2005

Completion Date:

December 2009

Related Keywords:

  • Pancreatic Cancer
  • 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
  • Pancreatic Neoplasms