Trial Outcomes & Findings for A Trial of Maintenance ADAPT Therapy With Capecitabine and Celecoxib in Patients With Metastatic Colorectal Cancer (NCT NCT01729923)

Results Overview

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

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

3 years

Results posted on

2018-01-16

Participant Flow

This study was activated on March 30, 2013 and terminated on August 12, 2016 due to lack of funding and prior to reaching its enrollment goal. A total 27 participants were accrued.

Participant milestones

Participant milestones
Measure	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. Capecitabine: Given PO Celecoxib: Given PO Intensity-Modulated Radiation Therapy: Undergo IMRT Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Radiation Therapy: Undergo radiation therapy Stereotactic Radiosurgery: Undergo stereotactic radiosurgery Therapeutic Conventional Surgery: Undergo surgical resection
Overall Study STARTED	27
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	27

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Capecitabine, Celecoxib, Radiation Therapy) n=27 Participants 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. Capecitabine: Given PO Celecoxib: Given PO Intensity-Modulated Radiation Therapy: Undergo IMRT Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Radiation Therapy: Undergo radiation therapy Stereotactic Radiosurgery: Undergo stereotactic radiosurgery Therapeutic Conventional Surgery: Undergo surgical resection
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=99 Participants
Age, Categorical >=65 years	3 Participants n=99 Participants
Age, Continuous	46 years n=99 Participants
Sex: Female, Male Female	12 Participants n=99 Participants
Sex: Female, Male Male	15 Participants n=99 Participants
Region of Enrollment United States	27 Participants n=99 Participants

PRIMARY outcome

Timeframe: 3 years

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

Outcome measures

Outcome measures
Measure	Capecitabine and Celecoxib n=27 Participants Patients are treated with oral capecitabine and celecoxib twice daily 7 days per week. Radiation therapy may be used for selected patients. During radiation, treatment with oral capecitabine and celecoxib will be given twice daily 5 days per week. Surgery may also be used for selected patients.
Rate of CR, Assessed According to CEA and CA 19-9 Measurements and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	1 Participants

SECONDARY outcome

Timeframe: Serial measures at 9 week intervals up to 5 years

Population: All patients who had RECIST measures at baseline and at least one other time point.

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.

Outcome measures

Outcome measures
Measure	Capecitabine and Celecoxib n=19 Participants Patients are treated with oral capecitabine and celecoxib twice daily 7 days per week. Radiation therapy may be used for selected patients. During radiation, treatment with oral capecitabine and celecoxib will be given twice daily 5 days per week. Surgery may also be used for selected patients.
Best Overall Response Rate Among All Patients Who Had RECIST Measurements at Baseline and at Least One Subsequent Occasion	-17 percentage of baseline lesion size Interval -100.0 to 75.6

SECONDARY outcome

Timeframe: Serial measures at 9 week intervals up to 5 years

Population: 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.

Outcome measures

Outcome measures
Measure	Capecitabine and Celecoxib n=8 Participants Patients are treated with oral capecitabine and celecoxib twice daily 7 days per week. Radiation therapy may be used for selected patients. During radiation, treatment with oral capecitabine and celecoxib will be given twice daily 5 days per week. Surgery may also be used for selected patients.
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	11 percentage of baseline lesion size Interval -31.2 to 75.6

SECONDARY outcome

Timeframe: Up to 5 years

Population: K-ras mutation status was not collected.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Until death or last reported survival, up to 5 years

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.

Outcome measures

Outcome measures
Measure	Capecitabine and Celecoxib n=27 Participants Patients are treated with oral capecitabine and celecoxib twice daily 7 days per week. Radiation therapy may be used for selected patients. During radiation, treatment with oral capecitabine and celecoxib will be given twice daily 5 days per week. Surgery may also be used for selected patients.
Overall Survival	15 months Interval 2.0 to 30.0

SECONDARY outcome

Timeframe: Up to 5 years

Population: We have been unable to confirmation that the original Principal Investigator secured the appropriate permission to use this instrument. Therefore, we are unable to use the data.

Group differences in QOL will be estimated, with repeated measures used to improve precision of estimates.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 5 years

Population: Measure Description: Inclusive of subject still alive at time of last reporting Time Frame: Until last reported survival Study terminated; data not further analyzed

Relapse-free survival estimated using the Kaplan-Meier method based on the ITT population starting from the time of induction chemotherapy initiation.

Outcome measures

Outcome measures
Measure	Capecitabine and Celecoxib n=1 Participants Patients are treated with oral capecitabine and celecoxib twice daily 7 days per week. Radiation therapy may be used for selected patients. During radiation, treatment with oral capecitabine and celecoxib will be given twice daily 5 days per week. Surgery may also be used for selected patients.
Relapse Free Survival in Patients Achieving CR	7 months

Adverse Events

Treatment (Capecitabine, Celecoxib, Radiation Therapy)

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Capecitabine, Celecoxib, Radiation Therapy) n=27 participants at risk 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. Capecitabine: Given PO Celecoxib: Given PO Intensity-Modulated Radiation Therapy: Undergo IMRT Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Radiation Therapy: Undergo radiation therapy Stereotactic Radiosurgery: Undergo stereotactic radiosurgery Therapeutic Conventional Surgery: Undergo surgical resection
Gastrointestinal disorders Nonoliguric Renal Failure	3.7% 1/27 • Number of events 1 • 3 years The adverse event recording period will start on the first day of study treatment and end 30 days after last protocol required treatment is administered. Only grade 2 and higher AEs will be recorded with the exception of any AE that requires a dose reduction or treatment interruption.

Other adverse events

Other adverse events
Measure	Treatment (Capecitabine, Celecoxib, Radiation Therapy) n=27 participants at risk 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. Capecitabine: Given PO Celecoxib: Given PO Intensity-Modulated Radiation Therapy: Undergo IMRT Laboratory Biomarker Analysis: Correlative studies Quality-of-Life Assessment: Ancillary studies Radiation Therapy: Undergo radiation therapy Stereotactic Radiosurgery: Undergo stereotactic radiosurgery Therapeutic Conventional Surgery: Undergo surgical resection
Gastrointestinal disorders Diarrhea	11.1% 3/27 • 3 years The adverse event recording period will start on the first day of study treatment and end 30 days after last protocol required treatment is administered. Only grade 2 and higher AEs will be recorded with the exception of any AE that requires a dose reduction or treatment interruption.
General disorders Fatigue	14.8% 4/27 • 3 years The adverse event recording period will start on the first day of study treatment and end 30 days after last protocol required treatment is administered. Only grade 2 and higher AEs will be recorded with the exception of any AE that requires a dose reduction or treatment interruption.
Skin and subcutaneous tissue disorders Hand/Foot Syndrome	48.1% 13/27 • 3 years The adverse event recording period will start on the first day of study treatment and end 30 days after last protocol required treatment is administered. Only grade 2 and higher AEs will be recorded with the exception of any AE that requires a dose reduction or treatment interruption.
Gastrointestinal disorders Post-Operative Pain	7.4% 2/27 • 3 years The adverse event recording period will start on the first day of study treatment and end 30 days after last protocol required treatment is administered. Only grade 2 and higher AEs will be recorded with the exception of any AE that requires a dose reduction or treatment interruption.
Gastrointestinal disorders Abdominal Pain	7.4% 2/27 • 3 years The adverse event recording period will start on the first day of study treatment and end 30 days after last protocol required treatment is administered. Only grade 2 and higher AEs will be recorded with the exception of any AE that requires a dose reduction or treatment interruption.
Immune system disorders Lupus (autoimmune reaction)	7.4% 2/27 • 3 years The adverse event recording period will start on the first day of study treatment and end 30 days after last protocol required treatment is administered. Only grade 2 and higher AEs will be recorded with the exception of any AE that requires a dose reduction or treatment interruption.

Additional Information

Dr. Stacey Cohen, Principal Investigator

University of Washington

Phone: 206-606-6658

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place