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

Primary Purpose

Recurrent Colon Carcinoma, Recurrent Rectal Carcinoma, Stage IVA Colon Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Capecitabine
Celecoxib
Intensity-Modulated Radiation Therapy
Laboratory Biomarker Analysis
Quality-of-Life Assessment
Radiation Therapy
Stereotactic Radiosurgery
Therapeutic Conventional Surgery
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Colon Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (capecitabine, celecoxib, radiation therapy)

Arm Description

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.

Outcomes

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
Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level in response to ADAPT therapy.

Secondary Outcome Measures

Best Overall Response Rate Among All Patients Who Had RECIST Measurements at Baseline and at Least One Subsequent Occasion
RECIST 1.1 criteria will be used to measure changes in the size of a selected sentinel lesion for each patient. Computed tomographic images will be measured at baseline and at subsequent 9 week intervals. Changes will be measured as percentage of the baseline measure. Results will be reported as the largest negative change. For patients with no negative changes, results will be reported as the smallest positive change.
Best Overall Response Rate Among All Patients Who Had RECIST Measurements at Baseline and at Least One Subsequent Occasion and Did Not Have Surgery or Radiation Therapy
RECIST 1.1 criteria will be used to measure changes in the size of a selected sentinel lesion for each patient. Computed tomographic images will be measured at baseline and at subsequent 9 week intervals. Changes will be measured as percentage of the baseline measure. Results will be reported as the largest negative change. For patients with no negative changes, results will be reported as the smallest positive change.
K-ras Mutation Status
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.
Overall Survival
Estimated using the Kaplan-Meier method based on the ITT population starting from the time of induction chemotherapy initiation until death or last reported survival.
Quality of Life (QOL), Assessed Using the M.D. Anderson Symptom Inventory (MDASI)
Group differences in QOL will be estimated, with repeated measures used to improve precision of estimates.
Relapse Free Survival in Patients Achieving CR
Relapse-free survival estimated using the Kaplan-Meier method based on the ITT population starting from the time of induction chemotherapy initiation.

Full Information

First Posted
November 15, 2012
Last Updated
December 14, 2017
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01729923
Brief Title
A Trial of Maintenance ADAPT Therapy With Capecitabine and Celecoxib in Patients With Metastatic Colorectal Cancer
Acronym
ADAPT
Official Title
A Phase II Trial of Maintenance ADAPT Therapy With Capecitabine and Celecoxib in Patients With Metastatic Colorectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Terminated
Why Stopped
Funding ended
Study Start Date
March 2013 (undefined)
Primary Completion Date
September 6, 2016 (Actual)
Study Completion Date
September 6, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Colon Carcinoma, Recurrent Rectal Carcinoma, Stage IVA Colon Cancer, Stage IVA Rectal Cancer, Stage IVB Colon Cancer, Stage IVB Rectal Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (capecitabine, celecoxib, radiation therapy)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Ro 09-1978/000, Xeloda
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Celecoxib
Other Intervention Name(s)
Benzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-, Celebrex, SC-58635, YM 177
Intervention Description
Given PO
Intervention Type
Radiation
Intervention Name(s)
Intensity-Modulated Radiation Therapy
Other Intervention Name(s)
IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy
Intervention Description
Undergo IMRT
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Other Intervention Name(s)
Cancer Radiotherapy, Irradiate, Irradiated, Irradiation, RADIATION, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation
Intervention Description
Undergo radiation therapy
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Radiosurgery
Other Intervention Name(s)
Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, Stereotactic Radiation Therapy, Stereotactic Radiotherapy, stereotaxic radiation therapy, stereotaxic radiosurgery
Intervention Description
Undergo stereotactic radiosurgery
Intervention Type
Procedure
Intervention Name(s)
Therapeutic Conventional Surgery
Intervention Description
Undergo surgical resection
Primary Outcome Measure Information:
Title
Rate of CR, Assessed According to CEA and CA 19-9 Measurements and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Description
Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level in response to ADAPT therapy.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Best Overall Response Rate Among All Patients Who Had RECIST Measurements at Baseline and at Least One Subsequent Occasion
Description
RECIST 1.1 criteria will be used to measure changes in the size of a selected sentinel lesion for each patient. Computed tomographic images will be measured at baseline and at subsequent 9 week intervals. Changes will be measured as percentage of the baseline measure. Results will be reported as the largest negative change. For patients with no negative changes, results will be reported as the smallest positive change.
Time Frame
Serial measures at 9 week intervals up to 5 years
Title
Best Overall Response Rate Among All Patients Who Had RECIST Measurements at Baseline and at Least One Subsequent Occasion and Did Not Have Surgery or Radiation Therapy
Description
RECIST 1.1 criteria will be used to measure changes in the size of a selected sentinel lesion for each patient. Computed tomographic images will be measured at baseline and at subsequent 9 week intervals. Changes will be measured as percentage of the baseline measure. Results will be reported as the largest negative change. For patients with no negative changes, results will be reported as the smallest positive change.
Time Frame
Serial measures at 9 week intervals up to 5 years
Title
K-ras Mutation Status
Description
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.
Time Frame
Up to 5 years
Title
Overall Survival
Description
Estimated using the Kaplan-Meier method based on the ITT population starting from the time of induction chemotherapy initiation until death or last reported survival.
Time Frame
Until death or last reported survival, up to 5 years
Title
Quality of Life (QOL), Assessed Using the M.D. Anderson Symptom Inventory (MDASI)
Description
Group differences in QOL will be estimated, with repeated measures used to improve precision of estimates.
Time Frame
Up to 5 years
Title
Relapse Free Survival in Patients Achieving CR
Description
Relapse-free survival estimated using the Kaplan-Meier method based on the ITT population starting from the time of induction chemotherapy initiation.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stacey Cohen
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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