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Adenocarcinoma of the EsophagusPhase 2NCT01212822

Bevacizumab and Combination Chemotherapy Before Surgery in Treating Patients With Locally Advanced Esophageal or Stomach Cancer

A Phase 2 study testing bevacizumab, oxaliplatin and leucovorin calcium in people with Adenocarcinoma of the Esophagus and Adenocarcinoma of the Gastroesophageal Junction, run by Fox Chase Cancer Center at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This pilot phase II trial studies how well giving bevacizumab and combination chemotherapy together before surgery works in treating patients with locally advanced esophageal or stomach cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
bevacizumab, oxaliplatin and leucovorin calcium
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
3 sitesUnited States
Study dates
27 Apr 2011to 3 Jan 2018
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

  • Patients must have biopsy proven adenocarcinoma, squamous cell carcinoma or undifferentiated carcinoma of the esophagus, GE junction and/or gastric cardia
  • Patients must have potentially resectable disease by the thoracic, minimally invasive or transhiatal approach
  • No portion of the lesion may be within 5 cm of the cricopharyngeus
  • Patient must be considered medically fit for surgery with average or below average risk
  • T1-3 or T4 with local invasion confined to diaphragm, pleura or pericardium
  • No myocardial infarction within 12 months of enrollment
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  • Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • White blood cells (WBC) >= 3,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Serum creatinine (Cr) =< 1.5 mg and/or creatinine clearance >= 60 cc/min
  • Bilirubin must be < upper limit of normal (ULN) unless the patient has a chronic grade 1 bilirubin elevation due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin
  • Alkaline phosphatase must be < ULN
  • Aspartate aminotransferase (AST) \& alanine aminotransferase (ALT) must be < ULN
  • Urine protein/creatinine (UPC) ratio of < 1.0 or dipstick for protein of < 2+, Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v 4) grade < 2; patients with a UPC ratio >= 1.0 or dipstick of 2+ must undergo a 24-hour urine collection and must demonstrate < 1 gm of protein in order to participate
  • Patients must give written informed consent and Health Insurance Portability and Accountability Act (HIPAA) consent

Who cannot join

  • Patients with prior chemotherapy for any malignant disorder, thoracic radiotherapy or prior surgical resection of an esophageal tumor are ineligible
  • Patients with biopsy-proven invasion of the tracheobronchial tree or tracheo-esophageal fistula are ineligible
  • Patients with a history of a curatively treated malignancy must be disease-free for at least two years and have a survival prognosis that is greater than five years
  • Eligible patients of reproductive potential (both sexes) must agree to use an accepted and effective method of contraceptive during study therapy and for at least 6 months after the completion of bevacizumab; women must not be pregnant or breast-feeding because the study drugs administered may cause harm to an unborn fetus or breastfeeding child; all females of childbearing potential must have a serum pregnancy test to rule out pregnancy within 7 days prior to registration
  • Patients with a history of hypertension must measure < 150/90 mmHg and be on a stable regimen of anti-hypertensive therapy; patients with a history of hypertension who have a blood pressure of 150/90 mmHg, or greater are not eligible; patients with a history of hypertension who have a blood pressure of < 150/90 mmHg but are not on a stable regimen of anti-hypertensive therapy, are not eligible
  • Any prior history of hypertensive crisis or hypertensive encephalopathy
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  • New York Association (NYHA) grade II or greater congestive heart failure
  • Patients must not have a serious or non-healing wound, skin ulcers or unhealed bone fracture, or known human immunodeficiency virus (HIV) infection
  • Patients with >= grade 2 neuropathy are not eligible
  • Patients must not have had significant traumatic injury within 28 days prior to randomization
  • Patients with PT (INR) > 1.5 are not eligible; the patient may not be receiving full-dose anticoagulation; prophylactic or full dose anticoagulation are permitted post-resection or for treatment of an intercurrent thrombotic event
  • Patients with non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude any of the study therapy drugs are not eligible; specifically excluded are the following conditions: current symptomatic arrhythmia, symptomatic peripheral vascular disease
  • Patients with a history of the following within 12 months of study entry are not eligible: arterial thromboembolic events, unstable angina
  • Any history of stroke or transient ischemic attack
  • Significant vascular disease (i.e. aortic dissection, aortic aneurysm)
  • Patients with psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude them from meeting the study requirements are not eligible
  • Distant metastases
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
  • Known hypersensitivity to any component of bevacizumab

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111-2497

  • University of Pittsburgh Cancer Institute

    Pittsburgh, Pennsylvania, 15232

Other trials in United States

About this study

Official title: Phase II Trial of Pre-operative Bevacizumab and FOLFOX Chemotherapy in Locally Advanced Esophageal Cancer

This pilot phase II trial studies how well giving bevacizumab and combination chemotherapy together before surgery works in treating patients with locally advanced esophageal or stomach cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab and combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To investigate two-year disease-free survival in patients with resectable esophageal and gastroesophageal (GE) junction cancer treated with perioperative bevacizumab and leucovorin calcium, fluorouracil, and oxaliplatin (FOLFOX).

SECONDARY OBJECTIVES:

  1. To assess, by pathological examination after surgical resection, complete and partial response to neoadjuvant therapy.

II. To characterize overall and progression free survival. III. To compare baseline and post-chemotherapy/bevacizumab tissues for biomarkers predicting response or resistance to this approach.

IV. To investigate safety in this setting.

OUTLINE:

NEOADJUVANT THERAPY: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1. Patients also receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-2. Treatment with bevacizumab repeats every 2 weeks for 4 courses and treatment with FOLFOX repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

SURGERY: Patients then undergo planned surgical resection 4-6 weeks after 6 courses of chemotherapy and at least 8 weeks since the last dose of bevacizumab.

ADJUVANT THERAPY: Beginning 8-10 weeks after surgery, patients receive bevacizumab IV, oxaliplatin IV, leucovorin calcium IV, and fluorouracil IV as in neoadjuvant therapy. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Medical subject headings
Adenocarcinoma Of Esophagus, Esophageal Squamous Cell Carcinoma, Esophageal Neoplasms, Stomach Neoplasms

What participants receive

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

  • bevacizumabBiological

    Also called anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

    Given IV

  • oxaliplatinDrug

    Also called 1-OHP, Dacotin, Dacplat, Eloxatin

    Given IV

  • leucovorin calciumDrug

    Also called CF, CFR, LV

    Given IV

  • fluorouracilDrug

    Also called 5-fluorouracil, 5-Fluracil, 5-FU

    Given IV

  • therapeutic conventional surgeryProcedure or surgery

    Undergo surgical resection

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01212822
Study groupRoleWhat they receive
Treatment (bevacizumab, FOLFOX)ExperimentalNEOADJUVANT THERAPY: Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1-2. Treatment with bevacizumab repeats every 2 weeks for 4 courses and treatment with FOLFOX repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Patients then undergo planned surgical resection 4-6 weeks after 6 courses of chemotherapy and at least 8 weeks since the last dose of bevacizumab. ADJUVANT THERAPY: Beginning 8-10 weeks after surgery, patients receive bevacizumab IV, oxaliplatin IV, leucovorin calcium IV, and fluorouracil IV as in neoadjuvant therapy. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
Receives: Biological: bevacizumab; Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis

What is being measured

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

  1. Disease-free Survival

    To investigate 2 year disease free survival in pts with resectable esophageal and GE junction cancer treated with perioperative bevaciumab and FOLFOX

    Measured: 2 years

Secondary outcomes (3)

  1. Complete and Partial Response to Neoadjuvant Therapy Based on the Response Evaluation Criteria in Solid Tumors (RECIST)

    To assess, by path examination after surgical resection, complete and partial response to neoadjuvant therapy. Characterized using proportions and 95% confidence intervals.

    Measured: Up to 3 years

  2. Overall Survival

    Characterized using Kaplan-Meier curves.

    Measured: 4.5 years

  3. Progression Free Survival

    Characterized using Kaplan-Meier curves. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions and a 5 mm absolute increase, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Measured: 3 years

Timeline

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

  1. First posted1 Oct 2010 (estimated)
  2. Study start27 Apr 2011
  3. Primary completion24 Oct 2014
  4. Study completion3 Jan 2018

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01212822
Sponsor's protocol ID
FER-GI-029
Other IDs
NCI-2013-00603, IRB#10-022, FER-GI-029, P30CA006927
Status last verified
Aug 2022
First submitted
29 Sep 2010
Last updated
7 Sep 2022
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bevacizumab, oxaliplatin and leucovorin calcium in people with Adenocarcinoma of the Esophagus and Adenocarcinoma of the Gastroesophageal Junction, run by Fox Chase Cancer Center at 3 sites 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 15 inclusion and 19 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: finished, as of the sponsor's last update on 7 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 7 Sep 2022). 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?

Disease-free Survival (time frame: 2 years). 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 NCT01212822.

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 7 Sep 2022.

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