Capecitabine and Celecoxib With or Without Radiation Therapy in Treating Patients With Colorectal Cancer Previously Treated With Fluorouracil

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Washington
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT01729923
First received: November 15, 2012
Last updated: May 13, 2014
Last verified: May 2014

November 15, 2012
May 13, 2014
March 2013
March 2019   (final data collection date for primary outcome measure)
Rate of CR, assessed according to CEA and CA 19-9 measurements and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01729923 on ClinicalTrials.gov Archive Site
  • Relapse free survival in patients achieving CR [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method based on the ITT population starting from the time of induction chemotherapy initiation.
  • PFS as defined by true disease progression (new sites of disease) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method based on the ITT population starting from the time of induction chemotherapy initiation.
  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method based on the ITT population starting from the time of induction chemotherapy initiation.
  • Best overall response rate, defined using RECIST 1.1 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The relationship between K-ras mutation, resection, and radiation and response to ADAPT therapy will be evaluated using Chi-squared analysis and Cox regression analysis.
  • K-ras mutation status [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The relationship between K-ras mutation, resection, and radiation and response to ADAPT therapy will be evaluated using Chi-squared analysis and Cox regression analysis.
  • Quality of life (QOL), assessed using the M.D. Anderson Symptom Inventory (MDASI) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Group differences in QOL will be estimated, with repeated measures used to improve precision of estimates.
  • Adverse events defined as any condition that appears or worsens after the subject is enrolled in an investigational study, graded by numerical score according to the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
    The number and percent of subjects reporting adverse events coded as grade 3 or greater will be summarized by treatment group and strata. Listings will be provided for all on-study deaths and adverse events that lead to withdrawal from study. Narratives of all serious adverse events and deaths on-study will be provided.
Same as current
Not Provided
Not Provided
 
Capecitabine and Celecoxib With or Without Radiation Therapy in Treating Patients With Colorectal Cancer Previously Treated With Fluorouracil
A Phase II Trial of Maintenance ADAPT Therapy With Capecitabine and Celecoxib in Patients With Metastatic Colorectal Cancer

This phase II trial studies how well capecitabine and celecoxib with or without radiation therapy works in treating patients with metastatic colorectal cancer previously treated with fluorouracil. 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. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving capecitabine and celecoxib together with radiation therapy may kill more tumor cells.

PRIMARY OBJECTIVES:

I. To determine the rate of complete response 2 years following the initiation of first line 5-FU (fluorouracil) based chemotherapy in patients with initially unresected metastatic colorectal cancer who are then treated on the activating cancer stem cells (CSCs) from dormancy and priming them for subsequent targeting (ADAPT) protocol.

SECONDARY OBJECTIVES:

I. To determine progression free survival (PFS), overall survival (OS), relapse free survival (if complete response [CR]) from initiation of first line 5-FU based chemotherapy based on intent to treat (ITT) analysis.

II. To determine the effects of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-ras) mutation status in response to ADAPT therapy.

OUTLINE:

Patients proceed to surgery, radiation therapy with ADAPT therapy followed by maintenance ADAPT therapy, or ADAPT therapy. Eligible patients undergo surgical resection at baseline or upon achievement of resectable disease after radiation therapy.

RADIATION + ADAPT: Patients undergo radiation therapy 5 days per week and receive capecitabine orally (PO) twice daily (BID) and celecoxib PO BID 5 days per week during radiation.

ADAPT: Patients receive capecitabine PO BID on days 1-14 and celecoxib PO BID on days 1-21. Courses repeat every 21 days for up to 3 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 2 years, and then every 6 months for 2 years.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Colon Cancer
  • Recurrent Rectal Cancer
  • Stage IVA Colon Cancer
  • Stage IVA Rectal Cancer
  • Stage IVB Colon Cancer
  • Stage IVB Rectal Cancer
  • Drug: capecitabine
    Given PO
    Other Names:
    • CAPE
    • Ro 09-1978/000
    • Xeloda
  • Drug: celecoxib
    Given PO
    Other Names:
    • Celebrex
    • SC-58635
  • Radiation: radiation therapy
    Undergo radiation therapy
    Other Names:
    • irradiation
    • radiotherapy
    • therapy, radiation
  • Procedure: therapeutic conventional surgery
    Undergo surgical resection
  • Other: laboratory biomarker analysis
    Correlative studies
  • Procedure: quality-of-life assessment
    Ancillary studies
    Other Name: quality of life assessment
  • Radiation: intensity-modulated radiation therapy
    Undergo IMRT
    Other Name: IMRT
  • Radiation: stereotactic body radiation therapy
    Undergo SBRT
    Other Names:
    • SBRT
    • stereotactic radiation therapy
    • stereotactic radiotherapy
Experimental: Treatment (capecitabine, celecoxib, radiation therapy)

Patients proceed to surgery, radiation therapy with ADAPT therapy followed by maintenance ADAPT therapy, or ADAPT therapy. Eligible patients undergo surgical resection at baseline or upon achievement of resectable disease after radiation therapy.

RADIATION + ADAPT: Patients undergo radiation therapy 5 days per week and receive capecitabine PO BID and celecoxib PO BID 5 days per week during radiation.

ADAPT: Patients receive capecitabine PO BID on days 1-14 and celecoxib PO BID on days 1-21. Courses repeat every 21 days for up to 3 years in the absence of disease progression or unacceptable toxicity.

Interventions:
  • Drug: capecitabine
  • Drug: celecoxib
  • Radiation: radiation therapy
  • Procedure: therapeutic conventional surgery
  • Other: laboratory biomarker analysis
  • Procedure: quality-of-life assessment
  • Radiation: intensity-modulated radiation therapy
  • Radiation: stereotactic body radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
43
Not Provided
March 2019   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed colorectal cancer
  • Measurable radiographic evidence of colorectal cancer
  • Patients with unresected metastases from colorectal cancer; patients may be either untreated with chemotherapy or currently receiving first-line 5-FU based chemotherapy (folinic acid-fluorouracil-irinotecan [FOLFIRI], capecitabine-irinotecan [CAPIRI], fluorouracil-leucovorin calcium-oxaliplatin [FOLFOX], or capecitabine-oxaliplatin [CAPOX] with or without bevacizumab) within 6 months of study entry date with at least stable disease radiographically; patients who received prior adjuvant chemotherapy with 5-FU, capecitabine, or FOLFOX are eligible if adjuvant therapy was completed greater than 6 months ago
  • History of histological confirmation for recurrent disease, or if recurrent disease is not readily accessible to biopsy, must have two consecutive carcinoembryonic antigen (CEA) or cancer antigen (CA) 19-9 increases, or positron emission tomography (PET) avidity
  • Men and women from all ethnic and racial groups
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Total bilirubin =< 1.5 x the institutional upper-normal limit (IUNL)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and/or alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x IUNL
  • Alkaline phosphatase =< 2.5 x IUNL
  • Leukocytes >= 3,000/uL
  • Absolute neutrophil count >= 1,000/uL
  • Platelets >= 100,000/uL
  • Women of childbearing age and all men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation
  • Negative urine pregnancy test for women of childbearing age
  • Must have the ability to understand and the willingness to provide a written informed consent to participate in the study

Exclusion Criteria:

  • History of allergies to sulfonamide, aspirin, any nonsteroidal anti inflammatory drugs (NSAIDS), 5-FU or celecoxib
  • Prior 5-FU-based adjuvant chemotherapy less than 6 months prior to study entry and any residual neuropathy > grade 2
  • Any regular use of cyclooxygenase-2 (COX-2) inhibitors as defined by 2-3 times per week
  • Use of aspirin is NOT an exclusion criteria as long as the daily dose does not exceed 325 mg daily; initiation of ADAPT therapy requires patient to discontinue aspirin for 18 months
  • Pregnant or lactating women
  • History of significant neurologic or psychiatric disorders, including dementia or seizures that would impede consent, treatment, or follow up
  • Any serious illness or medical condition that could affect participation on trial
  • Any uncontrolled congestive heart failure New York Heart Association class III or IV
  • Any uncontrolled hypertension, arrhythmia, or active angina pectoris
  • Any history of major myocardial infarction, stroke or transient ischemic attack (TIA); minor acute myocardial infarction (AMI) and patients who have had cardiac bypass free of symptoms for at least 2 years may be eligible at the discretion of the study chair
  • Serious uncontrolled active infection
  • Patients with creatinine clearance: < 50 mL/min are excluded from this protocol; capecitabine is contraindicated in severe renal impairment (clearance < 40 mL/min)
  • Inability to swallow oral medications or any medical conditions that may affect intestinal absorption of the study agent or inability to comply with oral medication
  • History of active peptic ulcer disease or major upper gastrointestinal (GI) bleed < 12 months; history of GI bleeding from the colorectal cancer primary is not an exclusion criteria
  • Use of warfarin is not allowed; patient is recommended to switch to low molecular weight heparin (LMWH) before participating in this study
  • Patients with any history of brain or bone metastasis or who have develop progressive disease on first line 5-FU based therapy
  • Current use of steroid medication
  • Patients with an obstructive synchronous colorectal tumor requiring up-front surgery or chemoradiation
  • Patients with partial or complete bowel obstruction due to abdominal carcinomatosis
Both
18 Years and older
No
United States
 
NCT01729923
7707, NCI-2012-02137, 7707, P30CA015704
No
University of Washington
University of Washington
National Cancer Institute (NCI)
Principal Investigator: Edward Lin Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
University of Washington
May 2014

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