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Esophageal NeoplasmsPhase 2OSI3650NCT00442507

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

A Phase 2 study testing Erlotinib and Avastin in people with Esophageal Neoplasms and Esophageal Diseases, run by Washington University School of Medicine at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Esophageal Neoplasms, Esophageal Diseases
What is being tested?
Erlotinib and Avastin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
Mar 2007to Jan 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: 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

Read the 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.

Being tested
Erlotinib, Avastin
Keywords
Esophagus, Esophagogastric Junction, Avastin, Bevacizumab, Erlotinib
Medical subject headings
Esophageal Neoplasms, Esophageal Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00442507
Study groupRoleWhat they receive
1ExperimentalPatients 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.
Receives: Drug: Erlotinib; Drug: Avastin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Median follow-up for TTP 6 weeks (6-18 weeks)

Secondary outcomes (3)

  1. Overall Survival Rate (OS)

    OS is defined as the time from initiation of treatment to the date of death for any reason.

    Measured: Median followup time from completion of treatment 325.5 days (44-401 days)

  2. 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.

    Measured: Median follow-up for response 6 weeks (6-18 weeks)

  3. Incidence and Severity of Toxicities

    Grade 3 and higher toxicities using CTCAE Version 3.0.

    Measured: Median follow-up time for toxicities 72 days (72 days-156 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Mar 2007 (estimated)
  2. Study startMar 2007
  3. Primary completionJan 2009
  4. Study completionJan 2009

Why it stopped: Slow accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00442507
Sponsor's protocol ID
06-1105
Acronym
OSI3650
Status last verified
Jul 2015
First submitted
1 Mar 2007
Last updated
24 Jul 2015
Data monitoring committee
No

Publications

  • 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.

    PubMed 15661684

  • 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.

    PubMed 15297948

  • 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.

    PubMed 12003198

  • 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.

    PubMed 8558192

  • 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.

    PubMed 12915869

  • 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.

    PubMed 12860957

  • 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.

    PubMed 15753456

  • 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.

    PubMed 16166415

  • 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.

    PubMed 16014882

  • Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971 Nov 18;285(21):1182-6. doi: 10.1056/NEJM197111182852108. No abstract available.

    PubMed 4938153

  • 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.

    PubMed 1688381

  • 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.

    PubMed 9002234

  • 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.

    PubMed 10628376

  • 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.

    PubMed 9377574

  • 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.

    PubMed 9403702

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Erlotinib and Avastin in people with Esophageal Neoplasms and Esophageal Diseases, run by Washington University School of Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jul 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to Progression (TTP) (time frame: Median follow-up for TTP 6 weeks (6-18 weeks)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00442507, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2015.

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OSI3650 Clinical Trial NCT00442507 | AzTrials