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Capecitabine With or Without Sunitinib Malate as First-Line Therapy in Treating Patients With Metastatic Cancer of the Esophagus or Gastroesophageal Junction

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00891878
Recruitment Status : Completed
First Posted : May 1, 2009
Results First Posted : July 24, 2018
Last Update Posted : July 24, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Tracking Information
First Submitted Date  ICMJE April 30, 2009
First Posted Date  ICMJE May 1, 2009
Results First Submitted Date  ICMJE February 15, 2017
Results First Posted Date  ICMJE July 24, 2018
Last Update Posted Date July 24, 2018
Study Start Date  ICMJE August 2009
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 28, 2018)
Comparison of Progression-free Survival [ Time Frame: Up to 3 years ]
The primary analysis will be a comparison of Arm A to Arm B using a one-sided log-rank test between the 2 Kaplan-Meier curves. All patients meeting the eligibility criteria, who started treatment will be considered evaluable for the primary endpoint. If a patient is still alive 3 years after registration, no further follow-up is required. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Original Primary Outcome Measures  ICMJE
 (submitted: April 30, 2009)
Comparison of Progression-free Survival
Change History Complete list of historical versions of study NCT00891878 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 28, 2018)
  • Response Rate (Complete Response or Partial Response) [ Time Frame: Up to 3 years ]
    A confirmed tumor response is defined to be a CR or PR noted as the objective status on 2 consecutive evaluations ≥4 weeks apart. Confirmed tumor response will be evaluated using the first 6 cycles of treatment. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response. The confirmed response rates between the 2 arms will be compared using a Chi-Square or Fisher's Exact test. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.
  • Overall Survival [ Time Frame: Up to 3 years ]
    Overall survival is defined as the time from randomization to death due to any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier.
  • Time to Disease Progression [ Time Frame: Up to 3 years ]
    Time to disease progression is defined as the time from randomization to the earliest date documentation of disease progression occurs. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time-to-progression will be estimated using the method of Kaplan-Meier.
  • Time to Treatment Failure [ Time Frame: Up to 3 years ]
    Time to treatment failure is defined to be the time from the date of randomization to the date at which the patient is removed from treatment due to progression, adverse events, or refusal.
  • Duration of Response [ Time Frame: Up to 3 years ]
    Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2009)
  • Response Rate (Complete Response or Partial Response)
  • Overall Survival
  • Time to Disease Progression
  • Time to Treatment Failure
  • Duration of Response
  • Adverse events
  • Crossover treatment analysis
  • Protein markers as predictors of tumor response
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Capecitabine With or Without Sunitinib Malate as First-Line Therapy in Treating Patients With Metastatic Cancer of the Esophagus or Gastroesophageal Junction
Official Title  ICMJE A Randomized Phase II Trial of Sunitinib Plus Capecitabine Versus Capecitabine Alone (With the Potential for Crossover) for Elderly and/or Poor Performance Status Patients With Metastatic Adenocarcinoma of the Esophagus or Gastroesophageal Junction
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sunitinib malate 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. It is not yet known whether capecitabine is more effective when given alone or together with sunitinib malate in treating patients with metastatic esophageal cancer or gastroesophageal junction cancer.

PURPOSE: This randomized phase II trial is studying how well capecitabine works compared with capecitabine given together with sunitinib malate as first-line therapy in treating patients with metastatic cancer of the esophagus or gastroesophageal junction.

Detailed Description

OBJECTIVES:

Primary

  • Compare the progression-free survival of elderly (age ≥ 65 years) and/or poor performance status patients with metastatic adenocarcinoma of the esophagus or gastroesophageal junction treated with capecitabine with verus without sunitinib malate.
  • Report other indicators of efficacy with these regimens, including the confirmed response rate, overall survival, time to tumor progression, duration of response, and time to treatment failure.
  • Compare the adverse event profiles of these regimens in these patients.

Secondary

  • Explore whether certain key proteins associated with anti-VEGF therapy are able to predict tumor response.
  • Bank paraffin-embedded tissue blocks or slides, and blood products for future studies.

OUTLINE: This is a multicenter study. Patients are stratified according to gender (male vs female), ECOG performance status (0 vs 1 vs 2), and age (≥ 65 years vs < 65 years). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral capecitabine twice daily on days 1-14. Patients experiencing disease progression may crossover to arm II at the physician's discretion.
  • Arm II: Patients receive oral capecitabine as in arm 1 and oral sunitinib malate once daily on days 1-21.

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Tumor tissue samples are collected at baseline for evaluation of protein markers as possible predictors of tumor response to this regimen. Samples are analyzed by IHC for expression levels of markers

After completion of study therapy, patients are followed periodically for 3 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adenocarcinoma of the Gastroesophageal Junction
  • Esophageal Cancer
Intervention  ICMJE
  • Drug: capecitabine
    Given orally
  • Drug: sunitinib malate
    Given orally
Study Arms  ICMJE
  • Experimental: Arm I
    Patients receive oral capecitabine twice daily on days 1-14. Patients experiencing disease progression may crossover to arm II at the physician's discretion.
    Intervention: Drug: capecitabine
  • Experimental: Arm II
    Patients receive oral capecitabine as in arm 1 and oral sunitinib malate once daily on days 1-21.
    Interventions:
    • Drug: capecitabine
    • Drug: sunitinib malate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 8, 2015)
12
Original Estimated Enrollment  ICMJE
 (submitted: April 30, 2009)
98
Actual Study Completion Date  ICMJE January 2013
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction

    • Metastatic disease
    • Unresectable disease with no curative options
  • Measurable disease with ≥ 1 lesion whose longest diameter can be accurately measured as ≥ 2.0 cm by conventional techniques or ≥ 1.0 cm by spiral CT
  • Not a candidate for a conventional multi-drug chemotherapy regimen with fairly standard dosing (i.e., patient is able to tolerate at least 80% of standard dosing)

    • Patients who have been offered and declined conventional multi-drug chemotherapy are eligible
  • No known CNS metastases

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-2 and age ≥ 65 years OR PS 2 and age ≥ 18 years but < 65 years
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Total bilirubin normal
  • Alkaline phosphatase ≤ 2 times upper limit of normal (ULN)
  • Creatinine ≤ 1.5 times ULN
  • Creatinine clearance ≥ 60mL/min
  • AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Willing to provide tissue samples for central review and research purposes
  • Able to swallow pills
  • No immunocompromised patients (other than related to the use of corticosteroids), including patients known to be HIV-positive
  • No co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • No uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness or social situations that would limit compliance with study requirements
  • No NYHA class III or IV heart failure
  • No uncontrolled hypertension except at the discretion of treating oncologist
  • No other active malignancy except for nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No known dihydropyrimidine dehydrogenase deficiency (DPD)

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy, radiotherapy, immunotherapy, or biological therapy for recurrent or metastatic cancer

    • Prior chemotherapy or radiotherapy are allowed if they had been administered as adjuvant or neoadjuvant therapy and a complete surgical resection of the original cancer had been achieved
  • No prior sunitinib malate
  • No prior radiotherapy to > 30% of the marrow cavity at any time
  • More then 4 weeks since prior major surgery
  • At least 12 days since prior and no concurrent CYP3A4 inducers, including rifampin, rifabutin, carbamazepine, phenobarbital, phenytoin, St. John's wort, efavirenz, and tipranavir
  • At least 7 days since prior and no concurrent CYP3A4 inhibitors, including azole antifungals (ketoconazole, itraconazole), clarithromycin, erythromycin, diltiazem, verapamil, HIV protease inhibitors (indinavir, saquinavir, ritonavir, atazanavir, nelfinavir), and delavirdine
  • No other concurrent specific treatment (other than hormonal therapy) in patients with a history of prior malignancy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00891878
Other Study ID Numbers  ICMJE NCCTG-N0747
NCI-2011-01920 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
CDR0000641212 ( Registry Identifier: PDQ (Physician Data Query) )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alliance for Clinical Trials in Oncology
Study Sponsor  ICMJE Alliance for Clinical Trials in Oncology
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Aminah Jatoi, MD Mayo Clinic
PRS Account Alliance for Clinical Trials in Oncology
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP