Trial Outcomes & Findings for Combination of Oxaliplatin, Capecitabine, and Celecoxib With Concurrent Radiation for Rectal Cancer (NCT NCT00250835)

Last Updated: 2015-09-01

Results Overview

The pathologic complete response (PCR) rate will be calculated as the proportion of patients who achieve complete response out of all evaluable patients. PCR is defined as the total absence of residual tumor cells by microscopic examination of the resected surgical specimen, including all of the sampled lymph nodes.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

38 participants

Primary outcome timeframe

At surgery (up to 6 weeks after end of treatment)

Results posted on

2015-09-01

Participant Flow

Subjects were recruited from participating cancer clinics across the state of New Mexico

Participant milestones

Participant milestones
Measure	Chemotherapy, Celecoxib, and Radiation Oxaliplatin weekly at 50 mg/m2 given intravenously over two hours for the duration of radiation. Capecitabine: on the days of radiation at 850 mg/m2 orally twice a day \[1700 mg/m2/day\] (Monday through Friday during radiation therapy). Celecoxib at 200 mg orally twice a day throughout the duration of radiation without a break. Chemotherapy, Celecoxib, and Radiation: Enrolled rectal cancer patients are treated with concurrent chemoradiation and celecoxib pre-operatively for at least 14 days. Definitive surgery is performed within 6 weeks from the end of treatment.
Overall Study STARTED	38
Overall Study COMPLETED	37
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Chemotherapy, Celecoxib, and Radiation Oxaliplatin weekly at 50 mg/m2 given intravenously over two hours for the duration of radiation. Capecitabine: on the days of radiation at 850 mg/m2 orally twice a day \[1700 mg/m2/day\] (Monday through Friday during radiation therapy). Celecoxib at 200 mg orally twice a day throughout the duration of radiation without a break. Chemotherapy, Celecoxib, and Radiation: Enrolled rectal cancer patients are treated with concurrent chemoradiation and celecoxib pre-operatively for at least 14 days. Definitive surgery is performed within 6 weeks from the end of treatment.
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Combination of Oxaliplatin, Capecitabine, and Celecoxib With Concurrent Radiation for Rectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chemotherapy, Celecoxib, and Radiation n=37 Participants Oxaliplatin weekly at 50 mg/m2 given intravenously over two hours for the duration of radiation. Capecitabine: on the days of radiation at 850 mg/m2 orally twice a day \[1700 mg/m2/day\] (Monday through Friday during radiation therapy). Celecoxib at 200 mg orally twice a day throughout the duration of radiation without a break. Chemotherapy, Celecoxib, and Radiation: Enrolled rectal cancer patients are treated with concurrent chemoradiation and celecoxib pre-operatively for at least 14 days. Definitive surgery is performed within 6 weeks from the end of treatment.
Age, Continuous	52 years n=93 Participants
Sex: Female, Male Female	16 Participants n=93 Participants
Sex: Female, Male Male	21 Participants n=93 Participants
Region of Enrollment United States	37 participants n=93 Participants

PRIMARY outcome

Timeframe: At surgery (up to 6 weeks after end of treatment)

Population: Patients who continue on at least two of the three drugs for a minimum of 14 days are considered evaluable for the primary objective

Outcome measures

Outcome measures
Measure	Chemotherapy, Celecoxib, and Radiation n=32 Participants Oxaliplatin weekly at 50 mg/m2 given intravenously over two hours for the duration of radiation. Capecitabine: on the days of radiation at 850 mg/m2 orally twice a day \[1700 mg/m2/day\] (Monday through Friday during radiation therapy). Celecoxib at 200 mg orally twice a day throughout the duration of radiation without a break. Chemotherapy, Celecoxib, and Radiation: Enrolled rectal cancer patients are treated with concurrent chemoradiation and celecoxib pre-operatively for at least 14 days. Definitive surgery is performed within 6 weeks from the end of treatment.
Pathologic Complete Response (PCR)	31 percentage of evaluable participants Interval 16.0 to 50.0

SECONDARY outcome

Timeframe: Up to 3 years

All toxicities encountered during the study will be evaluated according to the grading system (0-5) NCI CTCAE (Common Terminology Criteria for Adverse Events) version 3.0. Toxicity will be reported as the proportion of subjects experiencing Grades 3,4, and 5 adverse events (AEs) out of all evaluable patients

Outcome measures

Outcome measures
Measure	Chemotherapy, Celecoxib, and Radiation n=32 Participants Oxaliplatin weekly at 50 mg/m2 given intravenously over two hours for the duration of radiation. Capecitabine: on the days of radiation at 850 mg/m2 orally twice a day \[1700 mg/m2/day\] (Monday through Friday during radiation therapy). Celecoxib at 200 mg orally twice a day throughout the duration of radiation without a break. Chemotherapy, Celecoxib, and Radiation: Enrolled rectal cancer patients are treated with concurrent chemoradiation and celecoxib pre-operatively for at least 14 days. Definitive surgery is performed within 6 weeks from the end of treatment.
Toxicity Grade 3 and 4 diarrhea	9 percentage of participants
Toxicity Grade 3 and 4 abnormal liver function tests	9 percentage of participants
Toxicity Grade 3 and 4 abdominal pain	6 percentage of participants
Toxicity Death (from severe infection)	6 percentage of participants

SECONDARY outcome

Timeframe: 3 years after surgery

The Response Evaluation Criteria In Solid Tumors (RECIST) guidelines (Version 1.0) will be used to determine tumor response and progression. Progressive disease (PD) for target lesions: \>= 20% increase in the sum of diameters of the target lesions taking as reference the smallest sum on study, and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered . PD for non-target lesions is defined as unequivocal appearance of one or more new malignant lesions or unequivocal progression of existing non-target lesions. Time to progression will be measured from the time of surgery or clinically documented down staging if surgery for whatever reason is not carried in the subject until there is evidence of PD. Progression-free survival is reported as the percentage of patients who have not experienced progression of disease at three years post-surgery

Outcome measures

Outcome measures
Measure	Chemotherapy, Celecoxib, and Radiation n=32 Participants Oxaliplatin weekly at 50 mg/m2 given intravenously over two hours for the duration of radiation. Capecitabine: on the days of radiation at 850 mg/m2 orally twice a day \[1700 mg/m2/day\] (Monday through Friday during radiation therapy). Celecoxib at 200 mg orally twice a day throughout the duration of radiation without a break. Chemotherapy, Celecoxib, and Radiation: Enrolled rectal cancer patients are treated with concurrent chemoradiation and celecoxib pre-operatively for at least 14 days. Definitive surgery is performed within 6 weeks from the end of treatment.
Progression-free Survival (PFS)	84 percentage of evaluable participants Interval 65.0 to 93.0

SECONDARY outcome

Timeframe: At surgery (up to 6 weeks after end of treatment)

Incidence of sphincter-saving surgery is defined as the proportion of subjects who do not have permanent colostomy at the final follow-up out of all evaluable patients.

Outcome measures

Outcome measures
Measure	Chemotherapy, Celecoxib, and Radiation n=32 Participants Oxaliplatin weekly at 50 mg/m2 given intravenously over two hours for the duration of radiation. Capecitabine: on the days of radiation at 850 mg/m2 orally twice a day \[1700 mg/m2/day\] (Monday through Friday during radiation therapy). Celecoxib at 200 mg orally twice a day throughout the duration of radiation without a break. Chemotherapy, Celecoxib, and Radiation: Enrolled rectal cancer patients are treated with concurrent chemoradiation and celecoxib pre-operatively for at least 14 days. Definitive surgery is performed within 6 weeks from the end of treatment.
Incidence of Sphincter-sparing Surgery	56 percentage of evaluable participants Interval 38.0 to 74.0

SECONDARY outcome

Timeframe: At surgery (up to 6 weeks after treatment)

Downstaging rate after neoadjuvant treatment with combination oxaliplatin, capecitabine, celecoxib and concurrent radiation is defined as the proportion of patients whose pathological stage (stage at surgery) is different from their clinical stage (stage at baseline)

Outcome measures

Outcome measures
Measure	Chemotherapy, Celecoxib, and Radiation n=32 Participants Oxaliplatin weekly at 50 mg/m2 given intravenously over two hours for the duration of radiation. Capecitabine: on the days of radiation at 850 mg/m2 orally twice a day \[1700 mg/m2/day\] (Monday through Friday during radiation therapy). Celecoxib at 200 mg orally twice a day throughout the duration of radiation without a break. Chemotherapy, Celecoxib, and Radiation: Enrolled rectal cancer patients are treated with concurrent chemoradiation and celecoxib pre-operatively for at least 14 days. Definitive surgery is performed within 6 weeks from the end of treatment.
Surgical Downstaging Rate	75 percentage of evaluable participants Interval 57.0 to 89.0

SECONDARY outcome

Timeframe: Up to 3 years after surgery

Pelvic local control rate is defined as the proportion of subjects who have no evidence of pelvic recurrence (by standard clinical assessment, including CT scan and clinical examination) at the final follow-up evaluation, out of all evaluable patients

Outcome measures

Outcome measures
Measure	Chemotherapy, Celecoxib, and Radiation n=32 Participants Oxaliplatin weekly at 50 mg/m2 given intravenously over two hours for the duration of radiation. Capecitabine: on the days of radiation at 850 mg/m2 orally twice a day \[1700 mg/m2/day\] (Monday through Friday during radiation therapy). Celecoxib at 200 mg orally twice a day throughout the duration of radiation without a break. Chemotherapy, Celecoxib, and Radiation: Enrolled rectal cancer patients are treated with concurrent chemoradiation and celecoxib pre-operatively for at least 14 days. Definitive surgery is performed within 6 weeks from the end of treatment.
Pelvic Local Control Rate	6 percentage of evaluable participants

Adverse Events

Chemotherapy, Celecoxib, and Radiation

Serious events: 6 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Chemotherapy, Celecoxib, and Radiation n=37 participants at risk Oxaliplatin weekly at 50 mg/m2 given intravenously over two hours for the duration of radiation. Capecitabine: on the days of radiation at 850 mg/m2 orally twice a day \[1700 mg/m2/day\] (Monday through Friday during radiation therapy). Celecoxib at 200 mg orally twice a day throughout the duration of radiation without a break. Chemotherapy, Celecoxib, and Radiation: Enrolled rectal cancer patients are treated with concurrent chemoradiation and celecoxib pre-operatively for at least 14 days. Definitive surgery is performed within 6 weeks from the end of treatment.
Gastrointestinal disorders Dehydration	8.1% 3/37 • Number of events 3
Gastrointestinal disorders Diarrhea	5.4% 2/37 • Number of events 2
Infections and infestations Opportunistic Infection	2.7% 1/37 • Number of events 1
Renal and urinary disorders Renal failure	2.7% 1/37 • Number of events 1
Gastrointestinal disorders Small intestinal obstruction	2.7% 1/37 • Number of events 1

Other adverse events

Other adverse events
Measure	Chemotherapy, Celecoxib, and Radiation n=37 participants at risk Oxaliplatin weekly at 50 mg/m2 given intravenously over two hours for the duration of radiation. Capecitabine: on the days of radiation at 850 mg/m2 orally twice a day \[1700 mg/m2/day\] (Monday through Friday during radiation therapy). Celecoxib at 200 mg orally twice a day throughout the duration of radiation without a break. Chemotherapy, Celecoxib, and Radiation: Enrolled rectal cancer patients are treated with concurrent chemoradiation and celecoxib pre-operatively for at least 14 days. Definitive surgery is performed within 6 weeks from the end of treatment.
Blood and lymphatic system disorders Hemoglobin decreased	13.5% 5/37 • Number of events 5
Blood and lymphatic system disorders Leukocytes decreased	8.1% 3/37 • Number of events 12
Blood and lymphatic system disorders Lymphocytes decreased	10.8% 4/37 • Number of events 15
Blood and lymphatic system disorders Platelets decreased	5.4% 2/37 • Number of events 4
General disorders Fatigue	35.1% 13/37 • Number of events 18
General disorders Weight loss	13.5% 5/37 • Number of events 7
Skin and subcutaneous tissue disorders Decubitus ulcer (skin breakdown)	5.4% 2/37 • Number of events 2
Skin and subcutaneous tissue disorders Dermatitis due to radiation	16.2% 6/37 • Number of events 6
Skin and subcutaneous tissue disorders Pruritus (Itching)	5.4% 2/37 • Number of events 2
Skin and subcutaneous tissue disorders Rash	8.1% 3/37 • Number of events 3
Gastrointestinal disorders Anorexia	8.1% 3/37 • Number of events 3
Gastrointestinal disorders Constipation	13.5% 5/37 • Number of events 5
Gastrointestinal disorders Dehydration	13.5% 5/37 • Number of events 6
Gastrointestinal disorders Diarrhea	48.6% 18/37 • Number of events 27
Gastrointestinal disorders Nausea	37.8% 14/37 • Number of events 22
Gastrointestinal disorders Vomiting	8.1% 3/37 • Number of events 5
Gastrointestinal disorders Rectal hemorrhage	8.1% 3/37 • Number of events 4
Investigations Hyperbilirubinemia	5.4% 2/37 • Number of events 7
Investigations Hyperglycemia	5.4% 2/37 • Number of events 4
Investigations Hypoalbuminemia	18.9% 7/37 • Number of events 12
Investigations Hypocalcemia	10.8% 4/37 • Number of events 9
Investigations Hypokalemia	13.5% 5/37 • Number of events 7
Investigations Hypomagnesemia	8.1% 3/37 • Number of events 3
Investigations Hyponatremia	8.1% 3/37 • Number of events 3
Investigations Increased blood urea nitrogen	5.4% 2/37 • Number of events 2
Musculoskeletal and connective tissue disorders Muscle weakness	5.4% 2/37 • Number of events 2
Nervous system disorders Dizziness	10.8% 4/37 • Number of events 4
Nervous system disorders Insomnia	8.1% 3/37 • Number of events 3
Nervous system disorders Peripheral sensory neuropathy	24.3% 9/37 • Number of events 12
General disorders Abdominal pain	21.6% 8/37 • Number of events 8
General disorders Pain	5.4% 2/37 • Number of events 2
General disorders Pain in extremity	8.1% 3/37 • Number of events 3
General disorders Rectal pain	16.2% 6/37 • Number of events 7
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	5.4% 2/37 • Number of events 2
Renal and urinary disorders Cystitis (bladder inflammation)	5.4% 2/37 • Number of events 2
Renal and urinary disorders Dysuria (painful urination)	5.4% 2/37 • Number of events 2

Additional Information

Fa-Chyi Lee, MD

University of New Mexico

Phone: 5059250405

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place