- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00442507
Erlotinib and Avastin in Patients With Cancer of the Esophagus or Gastroesophageal Junction (OSI3650)
July 2, 2015 updated by: Washington University School of Medicine
A Phase II Trial of Erlotinib and Avastin in Previously Treated Patients With Cancer of the Esophagus or Gastroesophageal Junction
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
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
6
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Missouri
-
St. Louis, Missouri, United States, 63110
- Washington University School of Medicine
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
Patients will be treated with erlotinib 150 mg oral daily and Avastin 15 mg/kg intravenously each cycle of therapy (each cycle is 21 days or every 3 weeks).
The first infusion of Avastin will be administered over 90 minutes.
If tolerated, the second infusion will be given over 60 minutes and in 30 minutes for the subsequent treatments.
Treatment will be administered until disease progression or intolerable side effects.
|
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Progression (TTP)
Time Frame: Median follow-up for TTP 6 weeks (6-18 weeks)
|
|
Median follow-up for TTP 6 weeks (6-18 weeks)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival Rate (OS)
Time Frame: Median followup time from completion of treatment 325.5 days (44-401 days)
|
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)
|
Response Rate (Complete Response (CR), Partial Response (PR), and CR+PR)
Time Frame: Median follow-up for response 6 weeks (6-18 weeks)
|
|
Median follow-up for response 6 weeks (6-18 weeks)
|
Incidence and Severity of Toxicities
Time Frame: Median follow-up time for toxicities 72 days (72 days-156 days)
|
Grade 3 and higher toxicities using CTCAE Version 3.0.
|
Median follow-up time for toxicities 72 days (72 days-156 days)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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, Santabarbara 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. doi: 10.1056/NEJMoa050753.
- Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971 Nov 18;285(21):1182-6. doi: 10.1056/NEJM197111182852108. No abstract available.
- 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.
- 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. doi: 10.3322/canjclin.55.1.10. Erratum In: CA Cancer J Clin. 2005 Jul-Aug;55(4):259.
- Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990 Jan 3;82(1):4-6. doi: 10.1093/jnci/82.1.4. No abstract available.
- 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. doi: 10.1200/JCO.2003.01.504.
- 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.
- Borgstrom P, Gold DP, Hillan KJ, Ferrara N. Importance of VEGF for breast cancer angiogenesis in vivo: implications from intravital microscopy of combination treatments with an anti-VEGF neutralizing monoclonal antibody and doxorubicin. Anticancer Res. 1999 Sep-Oct;19(5B):4203-14.
- Shah MA, Schwartz GK. Treatment of metastatic esophagus and gastric cancer. Semin Oncol. 2004 Aug;31(4):574-87. doi: 10.1053/j.seminoncol.2004.04.013.
- 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. doi: 10.1023/a:1014476602804.
- Conroy T, Etienne PL, Adenis A, Wagener DJ, Paillot B, Francois 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. doi: 10.1200/JCO.1996.14.1.164.
- 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. doi: 10.1038/sj.bjc.6601168.
- Baselga J, Arteaga CL. Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol. 2005 Apr 10;23(11):2445-59. doi: 10.1200/JCO.2005.11.890. Epub 2005 Mar 7. Erratum In: J Clin Oncol. 2005 Sep 1;23(25):6281.
- 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. doi: 10.1158/1078-0432.CCR-05-0790.
- Ferrara N, Keyt B. Vascular endothelial growth factor: basic biology and clinical implications. EXS. 1997;79:209-32. doi: 10.1007/978-3-0348-9006-9_9. No abstract available.
- 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.
- 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.
- 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. doi: 10.1016/s0959-8049(02)00013-8.
- 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. doi: 10.1054/bjoc.2001.1936.
- Tew WP, Kelsen DP, Ilson DH. Targeted therapies for esophageal cancer. Oncologist. 2005 Sep;10(8):590-601. doi: 10.1634/theoncologist.10-8-590.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2007
Primary Completion (Actual)
January 1, 2009
Study Completion (Actual)
January 1, 2009
Study Registration Dates
First Submitted
March 1, 2007
First Submitted That Met QC Criteria
March 1, 2007
First Posted (Estimate)
March 2, 2007
Study Record Updates
Last Update Posted (Estimate)
July 24, 2015
Last Update Submitted That Met QC Criteria
July 2, 2015
Last Verified
July 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Head and Neck Neoplasms
- Esophageal Neoplasms
- Esophageal Diseases
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Protein Kinase Inhibitors
- Erlotinib Hydrochloride
- Bevacizumab
Other Study ID Numbers
- 06-1105
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Esophageal Neoplasms
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedStage IIIA Esophageal Adenocarcinoma | Stage IIIB Esophageal Adenocarcinoma | Stage IIIC Esophageal Adenocarcinoma | Stage IIB Esophageal Adenocarcinoma | Stage IB Esophageal Adenocarcinoma | Stage IIA Esophageal AdenocarcinomaUnited States
-
University Hospital, LilleFederation of Research in Surgery (FRENCH); French Eso-Gastric Tumors Working... and other collaboratorsCompleted
-
University of Michigan Rogel Cancer CenterGenentech, Inc.TerminatedLoco-regional Esophageal Cancer
-
Cancer Institute and Hospital, Chinese Academy...Peking University Cancer Hospital & InstituteRecruitingEsophageal Neoplasm Metastatic | Esophageal Cancer Stage IVbChina
-
Universitaire Ziekenhuizen KU LeuvenCompletedEsophageal Carcinoma (Squamous Cell Carcinoma - Adenocarcinoma)Belgium
-
National Cancer Institute (NCI)RecruitingNeoplasms | Esophageal Neoplasms | Esophagus Cancer | Esophagus Neoplasm | Neoplasms, Esophageal | Esophageal Cancer (EsC)United States
-
Tianjin Medical University Cancer Institute and...Sun Yat-sen University; Cancer Institute and Hospital, Chinese Academy of Medical... and other collaboratorsNot yet recruitingStage III Esophageal Cancer | Stage II Esophageal Cancer
-
Tianjin Medical University Cancer Institute and...UnknownStage III Esophageal Cancer | Stage II Esophageal CancerChina
-
Emory UniversityNovartisCompletedEsophageal Cancer | Neoplasms, EsophagealUnited States
-
OHSU Knight Cancer InstituteOregon Health and Science UniversityWithdrawnStage IIB Esophageal Cancer AJCC v7 | Stage III Esophageal Cancer AJCC v7 | Stage IIIA Esophageal Cancer AJCC v7 | Stage IIIB Esophageal Cancer AJCC v7 | Stage IIIC Esophageal Cancer AJCC v7
Clinical Trials on Erlotinib
-
National Cancer Institute (NCI)University of Chicago; City of Hope Medical Center; University of Southern California and other collaboratorsCompleted
-
AVEO Pharmaceuticals, Inc.Biodesix, Inc.TerminatedNon-small Cell Lung CancerKorea, Republic of, United States, Australia, Taiwan, Singapore, Hong Kong, Italy
-
M.D. Anderson Cancer CenterCompletedAdvanced CancersUnited States
-
PfizerCompletedCarcinoma, Non-Small-Cell LungUnited States
-
Fox Chase Cancer CenterMillennium Pharmaceuticals, Inc.TerminatedNon-small Cell Lung Cancer Metastatic | Non-small Cell Lung Cancer RecurrentUnited States
-
University of ChicagoNational Cancer Institute (NCI)CompletedMalignant Peritoneal MesotheliomaUnited States
-
Grupo de Investigación Clínica en Oncología RadioterapiaCompletedSquamous Cell Carcinoma of the Head and NeckSpain
-
Kyowa Kirin Co., Ltd.TerminatedNon-small-cell Lung CancerJapan
-
Merck Sharp & Dohme LLCCompleted
-
Duke UniversityBristol-Myers Squibb; Genentech, Inc.Completed