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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00891878
First received: April 30, 2009
Last updated: January 20, 2013
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of the Gastroesophageal Junction
Esophageal Cancer
Drug: capecitabine
Drug: sunitinib malate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Comparison of progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate (complete response or partial response) [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Time to disease progression [ Designated as safety issue: No ]
  • Time to treatment failure [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Adverse events [ Designated as safety issue: Yes ]
  • Crossover treatment analysis [ Designated as safety issue: No ]
  • Protein markers as predictors of tumor response [ Designated as safety issue: No ]

Estimated Enrollment: 98
Study Start Date: August 2009
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: capecitabine
Given orally
Experimental: Arm II
Patients receive oral capecitabine as in arm 1 and oral sunitinib malate once daily on days 1-21.
Drug: capecitabine
Given orally
Drug: sunitinib malate
Given orally

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00891878

  Show 182 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Study Chair: Aminah Jatoi, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00891878     History of Changes
Other Study ID Numbers: CDR0000641212, NCCTG-N0747
Study First Received: April 30, 2009
Last Updated: January 20, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adenocarcinoma of the esophagus
adenocarcinoma of the gastroesophageal junction
recurrent esophageal cancer
stage IV esophageal cancer
stage III esophageal cancer

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Sunitinib
Capecitabine
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on October 19, 2014