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A Trial of Maintenance ADAPT Therapy With Capecitabine and Celecoxib in Patients With Metastatic Colorectal Cancer

Information source: University of Washington
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Intervention: Capecitabine (Drug); Celecoxib (Drug); Intensity-Modulated Radiation Therapy (Radiation); Laboratory Biomarker Analysis (Other); Quality-of-Life Assessment (Other); Radiation Therapy (Radiation); Stereotactic Radiosurgery (Radiation); Therapeutic Conventional Surgery (Procedure)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Washington

Official(s) and/or principal investigator(s):
Edward Lin, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Summary

This phase II trial studies how well capecitabine and celecoxib with or without radiation therapy works in treating patients with colorectal cancer that is newly diagnosed or has been previously treated with fluorouracil, and has spread to other parts of the body (metastatic). 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.

Clinical Details

Official title: A Phase II Trial of Maintenance ADAPT Therapy With Capecitabine and Celecoxib in Patients With Metastatic Colorectal Cancer

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Rate of CR, assessed according to CEA and CA 19-9 measurements and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Secondary outcome:

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

Best overall response rate, defined using RECIST 1.1

K-ras mutation status

Overall survival

Quality of life (QOL), assessed using the M.D. Anderson Symptom Inventory (MDASI)

Relapse free survival in patients achieving CR

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 overall survival, relapse free survival (if complete response [CR]) based on intent to treat (ITT) analysis. II. To determine quality of life while on ADAPT therapy. III. To determine the effects of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-ras) mutation status, resection and radiation on 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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Histologically confirmed colorectal cancer

- Evaluable or 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 hydrochloride [FOLFIRI], capecitabine-irinotecan hydrochloride [CAPIRI], fluorouracil-leucovorin calcium-oxaliplatin [FOLFOX], or capecitabine-oxaliplatin [CAPOX] with or without bevacizumab) within 10 months of beginning ADAPT therapy 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 =< 2

- 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 potential and all men must agree to use adequate contraception

(hormonal or barrier method of birth control) prior to beginning ADAPT therapy and for the duration of study participation

- Negative urine pregnancy test for women of childbearing potential

- 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 beginning ADAPT

therapy 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 criterion 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 criterion

- 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 developed

progressive disease on first line 5-FU based therapy

- Current use of systemic 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

Locations and Contacts

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Seattle, Washington 98109, United States; Recruiting
Edward H. Lin, Phone: 206-288-6678, Email: elin@seattlecca.org
Edward H. Lin, Principal Investigator
Additional Information

Starting date: March 2013
Last updated: July 31, 2015

Page last updated: August 20, 2015

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