Colorectal Neoplasms
Conditions
Brief summary
This study compares in the first study period combination of Irinotecan with three different methods of administration by Fluoropyrimidine. (ie. infusion, bolus and oral). In the second period of study it compares FOLFIRI \[a chemotherapy regime that combines bolus irinotecan and leucovorin \[LV\] with infusional 5-fluorouracil (5-FU)\] + bevacizumab and mlFL + bevacizumab. Measures of efficacy and safety will be reported.
Interventions
DRUGModified Bolus 5-FU/LV with Irinotecan
Day 1 & 8: Irinotecan (125 mg/m2 IV over 90 minutes), LV (20 mg/m2 IV bolus), 5-FU (500 mg/m2 IV bolus). All chemotherapy cycles repeated every 3 weeks. Celecoxib/placebo treatment will commence on the same day as chemotherapy treatment (i.e. Day 1 of treatment on study). Celecoxib/placebo will be taken at a dose of 400 mg po BID \[two times a day\] (800 mg/day) and will continue daily without interruption (no rest period for celecoxib/placebo treatment).
Day 1 Bevacizumab 5mg/kg IV 90 minutes prior to irinotecan/LV Irinotecan 180 mg/m2 IV 90 minutes Leucovorin 400 mg/m2 IV 2 hours - given with irinotecan without mixing. I m m e d i a t e l y f o l l o w e d b y : 5-FU 400 mg/m2 IV bolus 5-FU 2400 mg/m2 IV Continuous infusion over 46 hours Every 2 weeks Amendment 2 Bevacizumab 5mg/kg IV 90 minutes prior to irinotecan/LV Irinotecan 180 mg/m2 IV 90 minutes Leucovorin 400 mg/m2 IV 2 hours - given with irinotecan without mixing. I m m e d i a t e l y f o l l o w e d b y : 5-FU 400 mg/m2 IV bolus 5-FU 2400 mg/m2 IV Continuous infusion over 46 hours Celecoxib/placebo 400 mg BID \[two times a day\] oral Every 2 weeks
DRUGmiFL + bevacizumab
Day 1 Bevacizumab 7.5mg/kg IV \*over 90 minutes - given prior to irinotecan, 5-FU, and leucovorin Irinotecan 125 mg/m2 IV over 90 minutes Leucovorin 20 mg/m2 IV bolus 5-FU 500 mg/m2 IV bolus Day 8 Irinotecan 125 mg/m2 IV over 90 minutes Leucovorin 20 mg/m2 IV bolus 5-FU 500 mg/m2 IV bolus Every 3 weeks Amendment 2 Day 1 Bevacizumab 7.5mg/kg IV over 90 minutes - given prior to irinotecan, 5-FU, and leucovorin Irinotecan 125 mg/m2 IV over 90 minutes Leucovorin 20 mg/m2 IV bolus 5-FU 500 mg/m2 IV bolus Celecoxib/placebo 400 mg BID \[two times a day\] oral Day 8 Irinotecan 125 mg/m2 IV over 90 minutes Leucovorin 20 mg/m2 IV bolus 5-FU 500 mg/m2 IV bolus Celecoxib/placebo -- 400 mg po BID \[two times a day\] continues daily without interruption Every 3 weeks
DRUGInfusional 5-FU/LV with Irinotecan
Day 1: Irinotecan (180 mg/m2) IV over 90 minutes, LV (racemic mixture 400 mg/m2) over 2 hours during irinotecan infusion but without mixing, immediately followed by 5-FU IV bolus (400 mg/m2) and 5-FU continuous infusion (2400 mg/m2) over 46 hours. FOLFIRI regimen is repeated every 2 weeks. Celecoxib/placebo treatment will commence on the same day at a dose of 400 mg po BID \[two times a day\](800 mg/day) and will continue daily without interruption (no rest period for celecoxib/placebo treatment).
DRUGOral Capecitabine with Irinotecan
Day 1: Irinotecan (250 mg/m2 IV) over 90 minutes; Day 1-14: capecitabine 1000 mg/m2 PO BID \[two times a day\] (28 single doses). All chemotherapy cycles repeated every 3 weeks. Celecoxib/placebo treatment will commence on the same day as chemotherapy treatment (i.e. Day 1 of treatment on study). Celecoxib/placebo will be taken at a dose of 400 mg po BID (800 mg/day) and will continue daily without interruption (no rest period for celecoxib/placebo treatment).
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of colorectal cancer (either newly diagnosed or recurrent disease) with evidence of metastatic disease. (Stage IV distant disease) * Present or past histological documentation of adenocarcinoma of the colon or rectum. The site of the primary lesion must be or have been confirmed endoscopically, radiologically, or surgically to be or have been in the large bowel. Patients with a history of colorectal cancer treated by surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless: * An interval of greater than five years has elapsed between the primary surgery and the development of metastatic disease. * The primary cancer was a Duke's A or B1. * Physicians should consider biopsy of lesions to establish the diagnosis of metastatic colorectal cancer in each case if there is substantial clinical ambiguity regarding the nature of source of apparent metastases.
Exclusion criteria
* Patients who received any prior systemic anticancer therapy for metastatic colorectal cancer (e.g., chemotherapy, antibody therapy, immunotherapy, gene therapy, vaccine therapy, cytokine therapy, or other experimental agents). * Patients cannot have concurrent malignancies at study entry. * Exceptions: Patients with prior non-colorectal malignancies will be eligible if they have been disease-free for ³ 3 years or are deemed at low risk for recurrence by their treating physician (e.g., early stage prostate cancer, melanoma or bladder cancer). Patients with squamous or basal cell carcinoma of the skin or in situ cervical cancer that have been effectively treated are eligible, even if these were diagnosed within 3 years before randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) at Primary Completion: FOLFIRI and mIFL | every 6 weeks until disease progression | Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response: FOLFIRI, mIFL and CapeIRI | every 6 weeks during chemotherapy until disease progression | A subject will be considered achieving an overall response if the subject has a sustained Complete Response (CR) or Partial Response (PR) for at least 4 weeks, confirmed by tumor assessments. (CR: Disappearance of all target lesions. PR: greater than or equal to 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the Pre-treatment sum LD. ) |
| Survival Time: FOLFIRI, mIFL and CapeIRI | assessed at least every week during treatment and at least every 3 months during follow-up | Survival time defined as time from date of randomization to date of death. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive. |
| 1 Year Survival: FOLFIRI, mIFL and CapeIRI | 1 year from date of randomization | Number of patients alive or dead at 1 year. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive. |
| Time to Progression : Celecoxib and Placebo | every 6 weeks until disease progression | Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD). |
| Overall Response: Celecoxib and Placebo | every 6 weeks during chemotherapy until disease progression | A subject will be considered achieving an overall response if the subject has a sustained CR or PR for at least 4 weeks, confirmed by tumor assessments. (Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): ≥ 30% decrease in the sum of the LD of target lesions, taking as reference the Pre-treatment sum LD. ) |
| Survival Time: Celecoxib and Placebo | assessed at least every week during treatment and at least every 3 months during follow-up | Survival time defined as time from date of randomization to date of death. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive. |
| Time to Progression: FOLFIRI, mIFL and CapeIRI | every 6 weeks until disease progression | Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD). |
| Overall Response: Bevacizumab With FOLFIRI, mIFL | every 6 weeks during chemotherapy until disease progression | A subject will be considered achieving an overall response if the subject has a sustained CR or PR for at least 4 weeks, confirmed by tumor assessments. (Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): ≥ 30% decrease in the sum of the LD of target lesions, taking as reference the Pre-treatment sum LD. ) |
| 1 Year Survival: Bevacizumab With FOLFIRI, mIFL | 1 year from date of randomization | Number of patients alive or dead at 1 year. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive. |
| Survival Time at Last Follow-Up Visit: Bevacizumab With FOLFIRI, mIFL | Last Follow-Up Visit | Survival time defined as time from date of randomization to date of death. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive. Zero subjects analyzed indicates median could not be analyzed based on number of subjects who died. |
| Dose Reduction Due to Treatment Emergent Adverse Events | Day 1; Day 8; and at end of every 3 treatment cycles for FOLFIRI; end of every 2 cycles for mIRI | Number of subjects that had at least one Treatment-Emergent Adverse Event (TEAE) that led to a dose reduction. TEAE includes all reported Adverse Events that occurred within 30 days of last study medication. |
| Overall Relative Dose Intensity of Irinotecan | End of treatment cycle | Relative dose intensity for a cycle was calculated as the percentage of the actual dose intensity of the cycle divided by the planned dose intensity of the cycle. Overall relative dose intensity was calculated as the average relative dose intensities over all cycles. (Dose intensity for each cycle was calculated as the actual dose level of the study medication received in that cycle divided by the number of weeks in the cycle.) |
| Time to Progression: Bevacizumab With FOLFIRI, mIFL | every 6 weeks until disease progression | Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD). |
Countries
Australia, Canada, New Zealand, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FOLFIRI + Celecoxib Irinotecan plus infusional 5-Fluorouracil(5-FU)/Leucovorin(LV) (FOLFIRI) with celecoxib | 71 |
| FOLFIRI + Placebo Irinotecan plus infusional 5-FU/LV (FOLFIRI) with placebo | 73 |
| mIFL + Celecoxib Modified irinotecan plus bolus 5-FU/LV (mIFL) with celecoxib | 69 |
| mIFL + Placebo Modified irinotecan plus bolus 5-FU/LV (mIFL) with placebo | 72 |
| CapeIRI + Celecoxib Irinotecan plus capecitabine (CapeIRI) with celecoxib | 73 |
| CapeIRI + Placebo Irinotecan plus capecitabine (CapeIRI) with placebo | 72 |
| Bevacizumab + FOLFIRI + Celecoxib Bevacizumab + Irinotecan plus infusional 5-FU/LV (FOLFIRI) with celecoxib | 27 |
| Bevacizumab + FOLFIRI + Placebo Bevacizumab + Irinotecan plus infusional 5-FU/LV (FOLFIRI) with placebo | 30 |
| Bevacizumab + mIFL + Celecoxib Bevacizumab + Modified irinotecan plus bolus 5-FU/LV (mIFL) with celecoxib | 30 |
| Bevacizumab + mIFL + Placebo Bevacizumab + Modified irinotecan plus bolus 5-FU/LV (mIFL)with placebo | 30 |
| Total | 547 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | >3 week delay treatment due toxicity | 6 | 2 | 1 | 2 | 7 | 3 | 2 | 1 | 3 | 0 |
| Overall Study | initiation other anti-cancer treatment | 4 | 3 | 4 | 3 | 1 | 1 | 2 | 2 | 3 | 3 |
| Overall Study | intercurrent non-cancer related illness | 0 | 0 | 2 | 0 | 1 | 3 | 1 | 0 | 1 | 1 |
| Overall Study | Other | 1 | 4 | 1 | 6 | 2 | 12 | 1 | 5 | 3 | 3 |
| Overall Study | Physician Decision | 10 | 13 | 6 | 7 | 8 | 9 | 5 | 5 | 1 | 1 |
| Overall Study | Progressive Disease | 37 | 28 | 37 | 38 | 28 | 25 | 5 | 7 | 10 | 8 |
| Overall Study | Randomized but did not receive treament | 1 | 6 | 2 | 2 | 2 | 2 | 0 | 1 | 0 | 1 |
| Overall Study | unacceptable toxicity | 3 | 9 | 10 | 6 | 16 | 10 | 4 | 2 | 1 | 4 |
| Overall Study | Withdrawal by Subject | 9 | 8 | 6 | 8 | 8 | 7 | 7 | 7 | 8 | 9 |
Baseline characteristics
| Characteristic | FOLFIRI + Celecoxib | FOLFIRI + Placebo | mIFL + Celecoxib | mIFL + Placebo | CapeIRI + Celecoxib | CapeIRI + Placebo | Bevacizumab + FOLFIRI + Celecoxib | Bevacizumab + FOLFIRI + Placebo | Bevacizumab + mIFL + Celecoxib | Bevacizumab + mIFL + Placebo | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | 61.0 years | 62.0 years | 61.0 years | 62.0 years | 62.0 years | 62.5 years | 59.0 years | 59.5 years | 61.0 years | 59.0 years | 61.0 years |
| Sex: Female, Male Female | 22 Participants | 30 Participants | 34 Participants | 24 Participants | 29 Participants | 37 Participants | 13 Participants | 14 Participants | 10 Participants | 12 Participants | 225 Participants |
| Sex: Female, Male Male | 49 Participants | 43 Participants | 35 Participants | 48 Participants | 44 Participants | 35 Participants | 14 Participants | 16 Participants | 20 Participants | 18 Participants | 322 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 135 / 137 | 137 / 137 | 140 / 141 | 56 / 56 | 58 / 59 |
| serious Total, serious adverse events | 50 / 137 | 52 / 137 | 78 / 141 | 19 / 56 | 21 / 59 |
Outcome results
Primary
Time to Progression (TTP) at Primary Completion: FOLFIRI and mIFL
Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD).
Time frame: every 6 weeks until disease progression
Population: Intent-to-Treat Population (ITT) - all subjects who were randomized, with study drug assignment designated according to initial randomization, regardless of whether subjects received any study drug or received a different drug from that to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOLFIRI | Time to Progression (TTP) at Primary Completion: FOLFIRI and mIFL | 8.18 months |
| mIFL | Time to Progression (TTP) at Primary Completion: FOLFIRI and mIFL | 6.01 months |
p-value: 0.015295% CI: [1.09, 1.89]Log Rank
Secondary
1 Year Survival: Bevacizumab With FOLFIRI, mIFL
Number of patients alive or dead at 1 year. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive.
Time frame: 1 year from date of randomization
Population: ITT Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FOLFIRI | 1 Year Survival: Bevacizumab With FOLFIRI, mIFL | Alive at 1 year | 45 participants |
| FOLFIRI | 1 Year Survival: Bevacizumab With FOLFIRI, mIFL | Dead at 1 year | 7 participants |
| FOLFIRI | 1 Year Survival: Bevacizumab With FOLFIRI, mIFL | Censored | 5 participants |
| mIFL | 1 Year Survival: Bevacizumab With FOLFIRI, mIFL | Alive at 1 year | 33 participants |
| mIFL | 1 Year Survival: Bevacizumab With FOLFIRI, mIFL | Dead at 1 year | 22 participants |
| mIFL | 1 Year Survival: Bevacizumab With FOLFIRI, mIFL | Censored | 5 participants |
Secondary
1 Year Survival: FOLFIRI, mIFL and CapeIRI
Number of patients alive or dead at 1 year. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive.
Time frame: 1 year from date of randomization
Population: ITT Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FOLFIRI | 1 Year Survival: FOLFIRI, mIFL and CapeIRI | Dead at 1 year | 34 participants |
| FOLFIRI | 1 Year Survival: FOLFIRI, mIFL and CapeIRI | Alive at 1 year | 101 participants |
| FOLFIRI | 1 Year Survival: FOLFIRI, mIFL and CapeIRI | Censored | 9 participants |
| mIFL | 1 Year Survival: FOLFIRI, mIFL and CapeIRI | Dead at 1 year | 47 participants |
| mIFL | 1 Year Survival: FOLFIRI, mIFL and CapeIRI | Alive at 1 year | 86 participants |
| mIFL | 1 Year Survival: FOLFIRI, mIFL and CapeIRI | Censored | 8 participants |
| CapeIRI | 1 Year Survival: FOLFIRI, mIFL and CapeIRI | Alive at 1 year | 89 participants |
| CapeIRI | 1 Year Survival: FOLFIRI, mIFL and CapeIRI | Censored | 10 participants |
| CapeIRI | 1 Year Survival: FOLFIRI, mIFL and CapeIRI | Dead at 1 year | 46 participants |
Secondary
Dose Reduction Due to Treatment Emergent Adverse Events
Number of subjects that had at least one Treatment-Emergent Adverse Event (TEAE) that led to a dose reduction. TEAE includes all reported Adverse Events that occurred within 30 days of last study medication.
Time frame: Day 1; Day 8; and at end of every 3 treatment cycles for FOLFIRI; end of every 2 cycles for mIRI
Population: As-Treated population - all subjects who received any study medication, with treatment assignments designated according to actual study treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFIRI | Dose Reduction Due to Treatment Emergent Adverse Events | 18 participants |
| mIFL | Dose Reduction Due to Treatment Emergent Adverse Events | 14 participants |
| CapeIRI | Dose Reduction Due to Treatment Emergent Adverse Events | 39 participants |
| Bevacizumab + FOLFIRI | Dose Reduction Due to Treatment Emergent Adverse Events | 6 participants |
| Bevacizumab + mIRI | Dose Reduction Due to Treatment Emergent Adverse Events | 8 participants |
Secondary
Overall Relative Dose Intensity of Irinotecan
Relative dose intensity for a cycle was calculated as the percentage of the actual dose intensity of the cycle divided by the planned dose intensity of the cycle. Overall relative dose intensity was calculated as the average relative dose intensities over all cycles. (Dose intensity for each cycle was calculated as the actual dose level of the study medication received in that cycle divided by the number of weeks in the cycle.)
Time frame: End of treatment cycle
Population: As-Treated population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FOLFIRI | Overall Relative Dose Intensity of Irinotecan | 93.9 percent dose intensity | Standard Error 0.6 |
| mIFL | Overall Relative Dose Intensity of Irinotecan | 94.5 percent dose intensity | Standard Error 0.6 |
| CapeIRI | Overall Relative Dose Intensity of Irinotecan | 93.8 percent dose intensity | Standard Error 0.7 |
| Bevacizumab + FOLFIRI | Overall Relative Dose Intensity of Irinotecan | 93.3 percent dose intensity | Standard Error 0.8 |
| Bevacizumab + mIRI | Overall Relative Dose Intensity of Irinotecan | 95.5 percent dose intensity | Standard Error 0.8 |
Secondary
Overall Response: Bevacizumab With FOLFIRI, mIFL
A subject will be considered achieving an overall response if the subject has a sustained CR or PR for at least 4 weeks, confirmed by tumor assessments. (Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): ≥ 30% decrease in the sum of the LD of target lesions, taking as reference the Pre-treatment sum LD. )
Time frame: every 6 weeks during chemotherapy until disease progression
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFIRI | Overall Response: Bevacizumab With FOLFIRI, mIFL | 33 participants |
| mIFL | Overall Response: Bevacizumab With FOLFIRI, mIFL | 32 participants |
95% CI: [44.08, 70.86]
95% CI: [40, 66.33]
p-value: 0.7388Cochran-Mantel-Haenszel
Secondary
Overall Response: Celecoxib and Placebo
A subject will be considered achieving an overall response if the subject has a sustained CR or PR for at least 4 weeks, confirmed by tumor assessments. (Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): ≥ 30% decrease in the sum of the LD of target lesions, taking as reference the Pre-treatment sum LD. )
Time frame: every 6 weeks during chemotherapy until disease progression
Population: ITT Population. Celecoxib participants were combined from FOLFIRI, mIRI, and Capecitabine treatments (not bevacizumab); Placebo participants were combined from FOLFIRI, mIRI, and Capecitabine treatments (not bevacizumab).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFIRI | Overall Response: Celecoxib and Placebo | 84 participants |
| mIFL | Overall Response: Celecoxib and Placebo | 101 participants |
95% CI: [32.83, 46.34]
95% CI: [39.76, 53.42]
p-value: 0.1559Cochran-Mantel-Haenszel
Secondary
Overall Response: FOLFIRI, mIFL and CapeIRI
A subject will be considered achieving an overall response if the subject has a sustained Complete Response (CR) or Partial Response (PR) for at least 4 weeks, confirmed by tumor assessments. (CR: Disappearance of all target lesions. PR: greater than or equal to 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the Pre-treatment sum LD. )
Time frame: every 6 weeks during chemotherapy until disease progression
Population: ITT Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FOLFIRI | Overall Response: FOLFIRI, mIFL and CapeIRI | 68 participants |
| mIFL | Overall Response: FOLFIRI, mIFL and CapeIRI | 61 participants |
| CapeIRI | Overall Response: FOLFIRI, mIFL and CapeIRI | 56 participants |
95% CI: [38.85, 55.71]
95% CI: [34.95, 51.86]
95% CI: [30.66, 47.06]
p-value: 0.4751Cochran-Mantel-Haenszel
p-value: 0.1591Cochran-Mantel-Haenszel
p-value: 0.4395Cochran-Mantel-Haenszel
Secondary
Survival Time at Last Follow-Up Visit: Bevacizumab With FOLFIRI, mIFL
Survival time defined as time from date of randomization to date of death. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive. Zero subjects analyzed indicates median could not be analyzed based on number of subjects who died.
Time frame: Last Follow-Up Visit
Population: ITT Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOLFIRI | Survival Time at Last Follow-Up Visit: Bevacizumab With FOLFIRI, mIFL | 27.99 months |
| mIFL | Survival Time at Last Follow-Up Visit: Bevacizumab With FOLFIRI, mIFL | 19.22 months |
p-value: 0.03795% CI: [1.12, 2.88]Log Rank
Secondary
Survival Time: Celecoxib and Placebo
Survival time defined as time from date of randomization to date of death. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive.
Time frame: assessed at least every week during treatment and at least every 3 months during follow-up
Population: ITT Population. Celecoxib participants were combined from FOLFIRI, mIRI, and Capecitabine treatments (not bevacizumab); Placebo participants were combined from FOLFIRI, mIRI, and Capecitabine treatments (not bevacizumab).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOLFIRI | Survival Time: Celecoxib and Placebo | 21.06 months |
| mIFL | Survival Time: Celecoxib and Placebo | 18.83 months |
p-value: 0.531695% CI: [0.86, 1.36]Log Rank
Secondary
Survival Time: FOLFIRI, mIFL and CapeIRI
Survival time defined as time from date of randomization to date of death. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive.
Time frame: assessed at least every week during treatment and at least every 3 months during follow-up
Population: ITT Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOLFIRI | Survival Time: FOLFIRI, mIFL and CapeIRI | 23.06 months |
| mIFL | Survival Time: FOLFIRI, mIFL and CapeIRI | 17.64 months |
| CapeIRI | Survival Time: FOLFIRI, mIFL and CapeIRI | 18.92 months |
p-value: 0.087995% CI: [0.96, 1.68]Log Rank
p-value: 0.276595% CI: [0.9, 1.58]Log Rank
p-value: 0.936495% CI: [0.8, 1.38]Log Rank
Secondary
Time to Progression: Bevacizumab With FOLFIRI, mIFL
Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD).
Time frame: every 6 weeks until disease progression
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOLFIRI | Time to Progression: Bevacizumab With FOLFIRI, mIFL | 11.17 months |
| mIFL | Time to Progression: Bevacizumab With FOLFIRI, mIFL | 8.31 months |
p-value: 0.283595% CI: [0.75, 2.15]Log Rank
Secondary
Time to Progression : Celecoxib and Placebo
Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD).
Time frame: every 6 weeks until disease progression
Population: ITT Population. Celecoxib participants were combined from FOLFIRI, mIRI, and Capecitabine treatments (not bevacizumab); Placebo participants were combined from FOLFIRI, mIRI, and Capecitabine treatments (not bevacizumab).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOLFIRI | Time to Progression : Celecoxib and Placebo | 6.64 months |
| mIFL | Time to Progression : Celecoxib and Placebo | 6.70 months |
p-value: 0.716395% CI: [0.86, 1.33]Log Rank
Secondary
Time to Progression: FOLFIRI, mIFL and CapeIRI
Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD).
Time frame: every 6 weeks until disease progression
Population: ITT Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FOLFIRI | Time to Progression: FOLFIRI, mIFL and CapeIRI | 7.62 months |
| mIFL | Time to Progression: FOLFIRI, mIFL and CapeIRI | 5.98 months |
| CapeIRI | Time to Progression: FOLFIRI, mIFL and CapeIRI | 5.82 months |
p-value: 0.004295% CI: [1.16, 1.97]Log Rank
p-value: 0.015695% CI: [1.04, 1.8]Log Rank
p-value: 0.465995% CI: [0.81, 1.38]Log Rank