Clinical trial NCT00260364: Combining Erlotinib Plus Bevacizumab and Gemcitabine Plus Capecitabine to Treat Advanced Pancreatic Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Keywords: 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
Lead sponsor: Royal Marsden NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Professor Cunningham's Clinical Research Fund
name: Hoffmann-La Roche
First posted: 2005-12-01
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Part A (Phase I): Dose-limiting Toxicity (DLT)
measure: Part B (Phase II): Overall response rate (complete response and partial response)
Secondary outcomes:
measure: The secondary efficacy objectives of the trial are: One year survival and median overall survival
measure: Progression free survival, Disease control rate.
measure: The secondary safety objectives are: Toxicity,Quality of life
measure: and Assessment of pain
Other outcomes:
Locations:
city: London and Surrey
country: United Kingdom
facility: The Royal Marsden Foundation Hospital NHS Trust
state: London
Study officials:
affiliation: The Royal Marsden Hospital NHS Foundation Trust
name: David Cunningham, MD, FRCP
role: PRINCIPAL_INVESTIGATOR
References: