Colorectal Neoplasms
Conditions
Keywords
metastatic, colorectal, cancer, initial therapy
Brief summary
The purpose of this study is to determine the objective response rate of patients with previously untreated metastatic colorectal cancer treated with the combination of cetuximab, capecitabine, and oxaliplatin with out without bevacizumab.
Detailed description
Research has shown that the more drug treatments patients with cancer of the colon or rectum receive, the longer they live. One uses the drugs capecitabine and oxaliplatin which all patients on this study will receive. Bevacizumab is an antibody which blocks blood flow to tumors and increases how long patients with colorectal cancer live. However, it can increase the risk of stroke and heart attack. Bevacizumab is currently a standard part of treatment for colorectal cancer. Cetuximab is an antibody which blocks a protein called EGFR which shrinks colorectal cancer. It may be helpful with initial chemotherapy and with bevacizumab. One goal of this study is to find out the response rate (chance of tumor shrinking) with two treatments for colorectal cancer. All patients will get capecitabine, oxaliplatin and cetuximab. Half will receive bevacizumab. All drugs in this study are approved to treat colorectal cancer. This research study is being done to find the best, safest way to combine these therapies.
Interventions
DRUGbevacizumab
Bevacizumab 7.5mg/kg IV day 1 of each 21 day cycle
DRUGcetuximab
Cetuximab 400mg/m2 IV initial dose (cycle 1 day 1 only), then 250mg/m2 IV weekly each 21 day cycle
DRUGOxaliplatin
Oxaliplatin 130mg/m2 IV day 1 every 21 days
DRUGCapecitabine
Capecitabine 850mg/m2 PO every 12 hours days 1-14 of each 21 day cycle
Sponsors
Fox Chase Cancer Center
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
* measurable metastatic adenocarcinoma of the colon or rectum * no prior systemic therapy for metastatic disease * adjuvant therapy must have been completed \>/=12 months prior to recurrence, prior radiotherapy permitted but must have been completed \> 6 months prior to study entry * must have tumor tissue available for EGFR and thymidine phosphorylase evaluation * ECOG PS 0-1 * age \>/= 18 * adequate organ function: WBC\>/=3,000, ANC \>/=1,500, platelets\>/= 100,000, total bilirubin \</= 1.5X ULN, AST&ALT \</= 2.5X ULN, create clearance \>/= 50mL/min * negative pregnancy test w/in 72 hours of treatment for women of child bearing potential * ability to understand and willing to sign written ICF * able to swallow and absorb oral medication
Exclusion criteria
* medical or psychiatric condition which would potentially pose risk to patient by participation (i.e. but not limited to:uncontrolled hypertension, MI w/in 6 months,CNS disease, pregnancy or nursing) * history of neoplasm (other than non-metastatic skin cancer or carcinoma in situ of cervix) w/in 5 years * surgical procedure (not including closed biopsy or access port placement), open biopsy, significant traumatic injury w/in 28 days of registration or anticipation of need for surgical procedure while on study, fine needle aspiration or core biopsy w/in 7 days of registration * urine protein:creatinine ration \>/=1.0 at screening * evidence of bleeding diathesis or coagulopathy (in absence of anticoagulation) * prior severe infusion reaction to MAB or allergic reaction to capecitabine or oxaliplatin * underlying neuropathy \>/= grade 2 * TIA or CVA w/in 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | every 6-9 weeks; from date of first study drug dose until off treatment date (median of 8 cycles; range <1-19) | Objective response rate calculated by the proportion of overall response: CR+PR. Patients were categorized by one of the following (1-4 per RECISTv1.0 criteria on CT, MRI, x-ray; 4-9 considered failure to respond/disease progression): 1. complete response (CR): Disappearance of all lesions 2. partial response (PR): \>=30% decrease in the sum of the longest diameter of target lesions (SoL); from baseline SoL 3. stable disease (SD): Neither PR, PD, or CR 4. progressive disease (PD): \>=20% increase in the SoL; from smallest SoL. Or appearance of new lesion 5. early death from malignant disease 6. early death from toxicity 7. early death from other cause 9\) unknown (not assessable, insufficient data) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) | every 6-9 weeks; from dose of first study drug to event | Per Response Evaluation Criteria In Solid Tumors (RECISTv1.0) assessed by CT, MRI, x-ray scan: Complete response (CR): Disappearance of all lesions Partial response (PR): \>=30% decrease in the sum of the longest diameter of target lesions (SoL); from baseline SoL Stable disease (SD): Neither PR, PD, or CR Progressive disease (PD): \>=20% increase in the SoL; from smallest SoL. Or appearance of new lesion |
| Overall Survival | From dose of first study drug to last timepoint known to be alive (median follow-up for all patients was 25.9 months) | Follow-up for survival to be done at 3 month intervals for 2 years, then 6 month intervals for up to 5 years from study registration |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab Cetuximab: 400 mg/m2 initial dose (cycle 1 day 1 only), then 250mg/m2 IV weekly of each 21 day cycle
Oxaliplatin: 130mg/m2 IV day 1 of each 21 day cycle
Capecitabine: 850mg/m2 PO every 12 hours days 1-14 of each 21 day cycle
Bevacizumab: 7.5mg/kg IV day 1 of each 21 day cycle | 12 |
| Cetuximab, Oxaliplatin, Capecitabine Cetuximab: 400 mg/m2 initial dose (cycle 1 day 1 only), then 250mg/m2 IV weekly of each 21 day cycle
Oxaliplatin: 130mg/m2 IV day 1 of each 21 day cycle
Capecitabine: 850mg/m2 PO every 12 hours days 1-14 of each 21 day cycle | 11 |
| Total | 23 |
Baseline characteristics
| Characteristic | Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Total | Cetuximab, Oxaliplatin, Capecitabine |
|---|---|---|---|
| Age, Continuous | 59 years | 59 years | 58 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 19 Participants | 11 Participants |
| Region of Enrollment United States | 12 Participants | 23 Participants | 11 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 1 Participants |
| Sex: Female, Male Male | 8 Participants | 18 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 12 | 10 / 11 |
| other Total, other adverse events | 12 / 12 | 11 / 11 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 |
Outcome results
Primary
Objective Response Rate (ORR)
Objective response rate calculated by the proportion of overall response: CR+PR. Patients were categorized by one of the following (1-4 per RECISTv1.0 criteria on CT, MRI, x-ray; 4-9 considered failure to respond/disease progression): 1. complete response (CR): Disappearance of all lesions 2. partial response (PR): \>=30% decrease in the sum of the longest diameter of target lesions (SoL); from baseline SoL 3. stable disease (SD): Neither PR, PD, or CR 4. progressive disease (PD): \>=20% increase in the SoL; from smallest SoL. Or appearance of new lesion 5. early death from malignant disease 6. early death from toxicity 7. early death from other cause 9\) unknown (not assessable, insufficient data)
Time frame: every 6-9 weeks; from date of first study drug dose until off treatment date (median of 8 cycles; range <1-19)
Population: One patient in Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab Arm was not evaluable for response due to patient discontinuing after experiencing a hypersensitivity reaction to cetuximab during the first treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Objective Response Rate (ORR) | Overall response | 4 Participants |
| Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Objective Response Rate (ORR) | Complete response | 1 Participants |
| Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Objective Response Rate (ORR) | Partial response | 3 Participants |
| Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Objective Response Rate (ORR) | Stable disease | 7 Participants |
| Cetuximab, Oxaliplatin, Capecitabine | Objective Response Rate (ORR) | Stable disease | 3 Participants |
| Cetuximab, Oxaliplatin, Capecitabine | Objective Response Rate (ORR) | Overall response | 8 Participants |
| Cetuximab, Oxaliplatin, Capecitabine | Objective Response Rate (ORR) | Partial response | 7 Participants |
| Cetuximab, Oxaliplatin, Capecitabine | Objective Response Rate (ORR) | Complete response | 1 Participants |
Secondary
Overall Survival
Follow-up for survival to be done at 3 month intervals for 2 years, then 6 month intervals for up to 5 years from study registration
Time frame: From dose of first study drug to last timepoint known to be alive (median follow-up for all patients was 25.9 months)
Population: One patient in Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab Arm was not evaluable for response due to patient discontinuing after experiencing a hypersensitivity reaction to cetuximab during the first treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Overall Survival | 18 months |
| Cetuximab, Oxaliplatin, Capecitabine | Overall Survival | 42.5 months |
Secondary
Time to Progression (TTP)
Per Response Evaluation Criteria In Solid Tumors (RECISTv1.0) assessed by CT, MRI, x-ray scan: Complete response (CR): Disappearance of all lesions Partial response (PR): \>=30% decrease in the sum of the longest diameter of target lesions (SoL); from baseline SoL Stable disease (SD): Neither PR, PD, or CR Progressive disease (PD): \>=20% increase in the SoL; from smallest SoL. Or appearance of new lesion
Time frame: every 6-9 weeks; from dose of first study drug to event
Population: One patient in Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab Arm was not evaluable for response due to patient discontinuing after experiencing a hypersensitivity reaction to cetuximab during the first treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Time to Progression (TTP) | 8.7 months |
| Cetuximab, Oxaliplatin, Capecitabine | Time to Progression (TTP) | 14.4 months |