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.
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
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.
- Conditions
- Esophageal Cancer
- 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 group | Role | What they receive |
|---|---|---|
| Sunitinib | Experimental | Sunitinib 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.
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)
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
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
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
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
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
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.
- First posted20 Jun 2008 (estimated)
- Study start30 Jun 2008
- Primary completion17 Sep 2013
- Study completion30 Dec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Esophageal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Tony Bekaii-Saab
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor-investigator, Tony Bekaii-Saab, Ohio State University Comprehensive Cancer Center
- Investigators
- Tanios Bekaii-Saab, MD, Principal investigator, Ohio State University
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
- Results posted
- Yes, on ClinicalTrials.gov
- 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
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Mechanistic Radiographic and Biologic Phase 2 Single Agent Study of Sunitinib Malate in Relapsed/Refractory Esophageal and Gastroesophageal Cancers
- ClinicalTrials.gov ID
- NCT00702884
- Acronym / sponsor ID
- OSU-07121
- Conditions
- Esophageal Cancer
- Keywords
- recurrent esophageal cancer, stage IIIA esophageal cancer, stage IIIB esophageal cancer, stage IIIC esophageal cancer, stage IV esophageal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Tony Bekaii-SaabUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 30 Jun 2008 (actual)
- Primary completion
- 17 Sep 2013 (actual)
- Study completion
- 30 Dec 2013 (actual)
- First posted
- 20 Jun 2008 (estimated)
- Results
- Posted 21 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sunitinib | Experimental | Drug: sunitinib malateSunitinib 37.5 mg daily for a 4 week cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sunitinib malateAlso: Sutent, SU011248 L-Malate salt, SU010398, PHA-290940ADSunitinib 37.5 mg daily for a 4 week cycle | Drug | Sunitinib |
Primary outcome
Progression-free Survival Rate
Time frame: up to 24 weeks
Complete response, partial response, and stable disease) as assessed by RECIST criteria at 24 weeks
6 secondary outcomes
Overall Response Rate
Time frame: up to 4 years
Median Overall Survival Time
Time frame: up to 4 years
Median Progression-free Survival Time
Time frame: up to 4 years
Frequency and Severity of Adverse Events
Time frame: up to 4 years
Change in Mean Vessel Density
Time frame: up to 4 years
Quantitative Assessment of Proliferating Tumor Cells and Apoptosis
Time frame: up to 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26151457Wu 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.
- JameslineLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tanios Bekaii-Saab, MD principal investigator
Ohio State University
1 site in 1 country: see every site and its status.
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.