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

Phase 2
18 Years
Open (Enrolling)
Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IVA Colon Cancer, Stage IVA Rectal Cancer, Stage IVB Colon Cancer, Stage IVB Rectal Cancer

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Trial Information

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


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.


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.


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

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.

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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

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

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

Edward Lin

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


United States: Federal Government

Study ID:




Start Date:

March 2013

Completion Date:

Related Keywords:

  • Recurrent Colon Cancer
  • Recurrent Rectal Cancer
  • Stage IVA Colon Cancer
  • Stage IVA Rectal Cancer
  • Stage IVB Colon Cancer
  • Stage IVB Rectal Cancer
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Colorectal Neoplasms



Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109