Erlotinib and Avastin in Patients With Cancer of the Esophagus or Gastroesophageal Junction

Esophageal Neoplasms Clinical Trial

— OSI3650  

Official title:

A Phase II Trial of Erlotinib and Avastin in Previously Treated Patients With Cancer of the Esophagus or Gastroesophageal Junction

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00442507
• Other study ID #: 06-1105
• Status: Terminated
• Phase: Phase 2
• First received: March 1, 2007
• Last updated: July 2, 2015
• Start date: March 2007
• Est. completion date: January 2009

Study information

• Verified date: July 2015
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Esophageal Diseases
• Esophageal Neoplasms

Intervention

Drug:
• Erlotinib

• Avastin

Locations

Country	Name	City	State
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (20)

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Ciardiello F, Caputo R, Damiano V, Caputo R, Troiani T, Vitagliano D, Carlomagno F, Veneziani BM, Fontanini G, Bianco AR, Tortora G. Antitumor effects of ZD6474, a small molecule vascular endothelial growth factor receptor tyrosine kinase inhibitor, with additional activity against epidermal growth factor receptor tyrosine kinase. Clin Cancer Res. 2003 Apr;9(4):1546-56. — View Citation

Conroy T, Etienne PL, Adenis A, Wagener DJ, Paillot B, François E, Bedenne L, Jacob JH, Seitz JF, Bleiberg H, Van Pottelsberghe C, Van Glabbeke M, Delgado FM, Merle S, Wils J. Phase II trial of vinorelbine in metastatic squamous cell esophageal carcinoma. European Organization for Research and Treatment of Cancer Gastrointestinal Treat Cancer Cooperative Group. J Clin Oncol. 1996 Jan;14(1):164-70. — View Citation

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Heath EI, Urba S, Marshall J, Piantadosi S, Forastiere AA. Phase II trial of docetaxel chemotherapy in patients with incurable adenocarcinoma of the esophagus. Invest New Drugs. 2002 Feb;20(1):95-9. — View Citation

Hirata A, Ogawa S, Kometani T, Kuwano T, Naito S, Kuwano M, Ono M. ZD1839 (Iressa) induces antiangiogenic effects through inhibition of epidermal growth factor receptor tyrosine kinase. Cancer Res. 2002 May 1;62(9):2554-60. — View Citation

Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin. 2005 Jan-Feb;55(1):10-30. Erratum in: CA Cancer J Clin. 2005 Jul-Aug;55(4):259. — View Citation

Johnson JR, Cohen M, Sridhara R, Chen YF, Williams GM, Duan J, Gobburu J, Booth B, Benson K, Leighton J, Hsieh LS, Chidambaram N, Zimmerman P, Pazdur R. Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Clin Cancer Res. 2005 Sep 15;11(18):6414-21. — View Citation

Jung YD, Mansfield PF, Akagi M, Takeda A, Liu W, Bucana CD, Hicklin DJ, Ellis LM. Effects of combination anti-vascular endothelial growth factor receptor and anti-epidermal growth factor receptor therapies on the growth of gastric cancer in a nude mouse model. Eur J Cancer. 2002 May;38(8):1133-40. — View Citation

Lordick F, von Schilling C, Bernhard H, Hennig M, Bredenkamp R, Peschel C. Phase II trial of irinotecan plus docetaxel in cisplatin-pretreated relapsed or refractory oesophageal cancer. Br J Cancer. 2003 Aug 18;89(4):630-3. — View Citation

Mendelsohn J, Baselga J. Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol. 2003 Jul 15;21(14):2787-99. Review. — View Citation

Petit AM, Rak J, Hung MC, Rockwell P, Goldstein N, Fendly B, Kerbel RS. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol. 1997 Dec;151(6):1523-30. — View Citation

Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, Ferrara N. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res. 1997 Oct 15;57(20):4593-9. — View Citation

Shah MA, Schwartz GK. Treatment of metastatic esophagus and gastric cancer. Semin Oncol. 2004 Aug;31(4):574-87. Review. — View Citation

Shaheen RM, Ahmad SA, Liu W, Reinmuth N, Jung YD, Tseng WW, Drazan KE, Bucana CD, Hicklin DJ, Ellis LM. Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors. Br J Cancer. 2001 Aug 17;85(4):584-9. — View Citation

Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. — View Citation

Tew WP, Kelsen DP, Ilson DH. Targeted therapies for esophageal cancer. Oncologist. 2005 Sep;10(8):590-601. Review. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Progression (TTP)	TTP is defined as the time from initiation of treatment to the date of documented progression.; The median of TTP with 95% confidence interval will be presented.; Progressive disease (target lesions) is defined as at least a 20% increase in the sum of the longest diameter of the target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.; Progressive disease (non-target lesions) is defined as appearance of one or more new lesions. Unequivocal progression of existing non-target lesions.	Median follow-up for TTP 6 weeks (6-18 weeks)	No
Secondary	Overall Survival Rate (OS)	OS is defined as the time from initiation of treatment to the date of death for any reason.	Median followup time from completion of treatment 325.5 days (44-401 days)	No
Secondary	Response Rate (Complete Response (CR), Partial Response (PR), and CR+PR)	CR = disappearance of all target lesions; PR = at least a 30% decrease in the sum of the LD of the target lesions taking as reference the baseline sum LD.	Median follow-up for response 6 weeks (6-18 weeks)	No
Secondary	Incidence and Severity of Toxicities	Grade 3 and higher toxicities using CTCAE Version 3.0.	Median follow-up time for toxicities 72 days (72 days-156 days)	Yes

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine