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Esophageal CancerPhase 2NCT00702884

Sunitinib in Treating Patients With Relapsed or Refractory Esophageal or Gastroesophageal Junction Cancer

A Phase 2 study testing sunitinib malate in people with Esophageal Cancer, run by Tony Bekaii-Saab at 1 site 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

RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well sunitinib works in treating patients with relapsed or refractory esophageal or gastroesophageal junction cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Esophageal Cancer
What is being tested?
sunitinib malate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
30 Jun 2008to 30 Dec 2013
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

DISEASE CHARACTERISTICS:

  • Histologically confirmed esophageal or gastroesophageal junction carcinoma that is not amenable to curative surgery or other curative therapy
  • Advanced, relapsed or refractory disease
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
  • No known brain metastases

PATIENT CHARACTERISTICS:

  • ECOG (Eastern Cooperative Oncology Group) performance status 0-1
  • Life expectancy > 12 weeks
  • WBC ≥ 3,000/μL
  • Absolute neutrophil count ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Serum calcium ≤ 12.0 mg/dL
  • Total bilirubin normal
  • AST (aspartate aminotransferase) and ALT (Alanine Aminotransferase) ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to, during, and for 28 days after completion of study treatment
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sunitinib malate
  • No ongoing cardiac dysrhythmias ≥ grade 2, atrial fibrillation of any grade, or prolongation of the QTc (corrected QT interval) interval to > 450 msec (for males) or > 470 msec (for females)
  • No hypertension that cannot be controlled by medications (i.e., systolic/diastolic blood pressure > 150/100 mm Hg despite optimal medical therapy)
  • No myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within the past 12 months
  • No cerebrovascular accident or transient ischemic attack within the past 12 months
  • No pulmonary embolism within the past 12 months
  • No condition that would impair the ability to swallow and retain sunitinib malate tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease)
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No serious or nonhealing wound, ulcer, or bone fracture
  • No pre-existing thyroid abnormality that cannot be maintained in the normal range with medication
  • No concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situation that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

  • Recovered from prior therapy
  • At least 4 weeks since prior radiotherapy or major surgery
  • At least 4 weeks since prior chemotherapy (6 weeks for mitomycin C, carmustine, or alkylating agents)
  • No more than 6 prior courses of an alkylating agent
  • No more than 450 mg/m² of prior doxorubicin hydrochloride or 900 mg/m² of prior epirubicin hydrochloride
  • No more than 2 lines of prior therapy in the metastatic setting
  • No prior anti-VEGF monoclonal antibodies, such as bevacizumab or aflibercept
  • No prior tyrosine kinase inhibitors with similar targets (e.g., sorafenib tosylate or axitinib)
  • No other concurrent investigational agents
  • No concurrent therapeutic doses of coumarin-derivative anticoagulants, such as warfarin
  • Warfarin at doses of ≤ 2 mg daily are allowed for prophylaxis of thrombosis
  • Low molecular weight heparin allowed provided PT/INR (Prothrombin time and international normalized ratio) is ≤ 1.5
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent agents with proarrhythmic potential (e.g., terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, and flecainide)

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Ohio State University Medical Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Mechanistic Radiographic and Biologic Phase 2 Single Agent Study of Sunitinib Malate in Relapsed/Refractory Esophageal and Gastroesophageal Cancers

RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PURPOSE: This phase II trial is studying how well sunitinib works in treating patients with relapsed or refractory esophageal or gastroesophageal junction cancer.

Read the detailed description

OBJECTIVES:

Primary

  • To determine the progression-free survival rate (complete response, partial response, and stable disease as defined by RECIST criteria [Response Evaluation Criteria in solid Tumors]) at 24 weeks in patients with relapsed or refractory esophageal or gastroesophageal junction cancer treated with sunitinib malate.

Secondary

  • To explore the predictive role of a hybrid imaging protocol that combines PET/CT (Positron emission tomography) scan simultaneously with dynamic contrast-enhanced MRI.
  • Correlate quantitative changes in mean vessel density, alterations in tumor cell proliferation, and apoptosis in tumor biopsy specimens with clinical outcome in these patients.
  • To evaluate the objective response as defined by RECIST criteria, median overall survival, and median progression-free survival of these patients.
  • To evaluate the toxicities of sunitinib malate in these patients.

OUTLINE: Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood and tumor tissue sample collection periodically for correlative laboratory studies. Tumor tissue samples are assessed by immunohistochemistry and TUNEL for detection and quantitation of mean vessel density, proliferating tumor cells, and apoptosis. Tumor tissue samples are also assessed by immunohistochemistry for MAPK levels. Blood samples are analyzed by ELISA for VEGF, PlGF, sVEGFR2, and sVEGFR3 levels. Patients also undergo PET/CT scan and dynamic contrast-enhanced MRI periodically for correlative studies.

After completion of study treatment, patients are followed for at least 6 months.

Being tested
sunitinib malate
Keywords
recurrent esophageal cancer, stage IIIA esophageal cancer, stage IIIB esophageal cancer, stage IIIC esophageal cancer, stage IV esophageal cancer
Medical subject headings
Esophageal Neoplasms

What participants receive

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

  • sunitinib malateDrug

    Also called Sutent, SU011248 L-Malate salt, SU010398, PHA-290940AD

    Sunitinib 37.5 mg daily for a 4 week cycle

Study groups in NCT00702884
Study groupRoleWhat they receive
SunitinibExperimentalSunitinib 37.5 mg daily for a 4 week cycle
Receives: Drug: sunitinib malate

What is being measured

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

  1. Progression-free Survival Rate

    Complete response, partial response, and stable disease) as assessed by RECIST criteria at 24 weeks

    Measured: up to 24 weeks

Secondary outcomes (6)
  1. Overall Response Rate

    The Overall Response Rate (ORR) was assessed using Partial Response + Complete Response for patients. Response and progression was evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0.

    Measured: up to 4 years

  2. Median Overall Survival Time

    The median overall survival time will be reported using the 95% confidence intervals for the parameters.

    Measured: up to 4 years

  3. Median Progression-free Survival Time

    Progression free survival was measured as the time from start of treatment to the first measurement of tumor growth.

    Measured: up to 4 years

  4. Frequency and Severity of Adverse Events

    The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for adverse event reporting.

    Measured: up to 4 years

  5. Change in Mean Vessel Density

    Quantitative assessment of proliferating tumor cells, and apoptosis, of the laboratory and radiographic correlates, the analyses will be purely explorative.

    Measured: up to 4 years

  6. Quantitative Assessment of Proliferating Tumor Cells and Apoptosis

    Biopsy sample taken from patients before and after treatment Apoptosis measures using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, which measures 3' nicked DNA. DNA is degraded in the early steps of apoptosis into low molecular weight (LMW) fragments and the production of single strand breaks in the high molecular weight DNA.Both of these features of apoptosis can be detected by labeling free 3'-OH termini with modified nucleotides, in our case this will be biotin-labeled dUTP. Terminal deoxynucleotidyl transferase (TdT) is an enzyme that labels blunt-ends of DNA breaks and can catalyze polymerization of nucleotides to free 3'-OH DNA ends in a template-independent manner. The newly incorporated nucleotides are detected by a secondary antibody, avidin-peroxidase. After substrate reaction, the stained cells can be detected and counted under a light microscope. Apoptotic cells will be fixed with formaldehyde which links LMW DNA

    Measured: up to 4 years

Timeline

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

  1. First posted20 Jun 2008 (estimated)
  2. Study start30 Jun 2008
  3. Primary completion17 Sep 2013
  4. Study completion30 Dec 2013

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
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00702884
Sponsor's protocol ID
OSU-07121
Other IDs
NCI-2011-03148
Status last verified
Jan 2017
First submitted
19 Jun 2008
Last updated
21 Mar 2017
Data monitoring committee
Yes

Publications

  • Wu C, Mikhail S, Wei L, Timmers C, Tahiri S, Neal A, Walker J, El-Dika S, Blazer M, Rock J, Clark DJ, Yang X, Chen JL, Liu J, Knopp MV, Bekaii-Saab T. A phase II and pharmacodynamic study of sunitinib in relapsed/refractory oesophageal and gastro-oesophageal cancers. Br J Cancer. 2015 Jul 14;113(2):220-5. doi: 10.1038/bjc.2015.197. Epub 2015 Jul 7.

    PubMed 26151457

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing sunitinib malate in people with Esophageal Cancer, run by Tony Bekaii-Saab 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?

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 21 Mar 2017. 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 21 Mar 2017). 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?

Progression-free Survival Rate (time frame: up to 24 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 NCT00702884, which also lists 1 linked publication.

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 21 Mar 2017.

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