Clinical trial NCT00442507: Erlotinib and Avastin in Patients With Cancer of the Esophagus or Gastroesophageal Junction
Official title: A Phase II Trial of Erlotinib and Avastin in Previously Treated Patients With Cancer of the Esophagus or Gastroesophageal Junction
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Esophageal Neoplasms
Esophageal Diseases
Keywords: Esophagus
Esophagogastric Junction
Avastin
Bevacizumab
Erlotinib
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2007-03-02
Enrollment: 6
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: Determine the time to progression for the combination of erlotinib and bevacizumab in patients with previously treated metastatic cancer of the esophagus or gastroesophageal junction

Detailed description: We postulate that the addition of bevacizumab may increase the efficacy of erlotinib in patients with metastatic esophageal cancer, without adding significant toxicity. The non-overlapping toxicity profiles may allow the administration of the maximum tolerated doses for both agents without additive toxicities with the goal of demonstrating synergistic clinical activity. This combination has been previously tested in two studies for other malignancies with good tolerance and encouraging results.

Eligibility criteria: Inclusion Criteria:

* Biopsy proven adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal junction.
* Metastatic or advanced inoperable disease previously treated with one prior chemotherapy regimen
* Age greater than 18 years.
* Performance status ECOG 0 to 1.
* Adequate hepatic and renal function, defined as:

  * Serum creatinine \<= 3.0 mg/dL;
  * Creatinine clearance \>= 45 mL/min.
  * Bilirubin \<= 1.5 x institutional normal;
  * ALT/AST \<= 3 x institutional normal.
* Patients must have measurable disease. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension. The longest diameter of measurable lesions must be \>= 20 mm with conventional techniques or \>= 10 mm with spiral CT scan. Lesions that are not considered measurable include: bone lesions, leptomeningeal disease, brain lesions, ascites, pericardial or pleural effusion, and tumors situated in a previously irradiated area.
* Use of effective means of contraception for both male and female patients with child-bearing potential.
* A 1 month wash-out period is required for all patients entering this study from a previous treatment regimen

Exclusion Criteria:

* Previous use of anti-EGFR or anti-VEGF therapy.
* Previous history of cancer. The patient with a prior malignancy is eligible for this study only if the patient meets the following criteria for a cancer survivor. A cancer survivor is eligible provided the following criteria are met: (1) patient has undergone potentially curative therapy for all prior malignancies, (2) patients have been considered disease free for at least 5 years (with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix).
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0; or anticipation of the need for major surgical procedure during the course of the study. (In the case of high risk procedures such as liver resection, thoracotomy, or neurosurgery, it is recommended that patient delay treatment with chemotherapy for at least 6 weeks and with bevacizumab at least 8 weeks after surgery).
* Radiation therapy within the last 2 weeks.
* Presence of central nervous system or brain metastases at any time.
* Serious, non-healing wound, ulcer, or bone fracture
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0; and/or minor surgical procedures such as fine needle aspiration or core biopsies within 7 days prior to day 0.
* Presence of coagulopathy or clinical history of significant hematemesis, melena, or hemoptysis related to the diagnosis of esophageal cancer.
* Previous history of deep venous thrombosis or thromboembolic disease.
* Urine protein/urine creatinine ratio ≥ 1.0 at screening.
* Pregnant or lactating.
* Unstable angina or history of myocardial infarction within the last 6 months.
* History of stroke within the last 6 months.
* Uncontrolled hypertension with blood pressure persistently \> 150/100 mmHg despite optimal antihypertensive therapy.
* Clinically significant peripheral vascular disease.
* Congestive heart failure with New York Heart Association grades III or IV (see appendix B).
* Inability to complete the study and follow-up procedures.
* Participation in therapeutic clinical trials or currently receiving other investigational treatment(s) within 30 days prior to enrollment

Primary outcomes:
measure: Time to Progression (TTP)
timeFrame: Median follow-up for TTP 6 weeks (6-18 weeks)
Secondary outcomes:
measure: Overall Survival Rate (OS)
timeFrame: Median followup time from completion of treatment 325.5 days (44-401 days)
measure: Response Rate (Complete Response (CR), Partial Response (PR), and CR+PR)
timeFrame: Median follow-up for response 6 weeks (6-18 weeks)
measure: Incidence and Severity of Toxicities
timeFrame: Median follow-up time for toxicities 72 days (72 days-156 days)
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Daniel Morgensztern, M.D.
role: PRINCIPAL_INVESTIGATOR
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