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
  Purpose

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.


Condition Intervention Phase
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage IVA Colon Cancer
Stage IVA Rectal Cancer
Stage IVB Colon Cancer
Stage IVB Rectal Cancer
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
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Maintenance ADAPT Therapy With Capecitabine and Celecoxib in Patients With Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 43
Study Start Date: March 2013
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Detailed Description:

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.

  Eligibility

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

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
  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: NCT01729923

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Edward H. Lin    206-288-6678      
Principal Investigator: Edward H. Lin         
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Edward Lin Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT01729923     History of Changes
Other Study ID Numbers: 7707, NCI-2012-02137, 7707, P30CA015704
Study First Received: November 15, 2012
Last Updated: May 13, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Colonic Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Celecoxib
Capecitabine
Fluorouracil
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014