Combination of Cetuximab, Capecitabine, and Oxaliplatin With or Without Bevacizumab
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab Cetuximab 400 mg/m2 IV 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 |
Drug: bevacizumab
Bevacizumab 7.5mg/kg IV day 1 of each 21 day cycle
Other Names:
Drug: cetuximab
Cetuximab 400mg/m2 IV initial dose (cycle 1 day 1 only), then 250mg/m2 IV weekly each 21 day cycle
Other Names:
Drug: Oxaliplatin
Oxaliplatin 130mg/m2 IV day 1 every 21 days
Other Names:
Drug: Capecitabine
Capecitabine 850mg/m2 PO every 12 hours days 1-14 of each 21 day cycle
Other Names:
|
Active Comparator: Cetuximab, Oxaliplatin, Capecitabine Cetuximab 400 mg/m2 IV 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 |
Drug: cetuximab
Cetuximab 400mg/m2 IV initial dose (cycle 1 day 1 only), then 250mg/m2 IV weekly each 21 day cycle
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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): 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 early death from malignant disease early death from toxicity early death from other cause 9) unknown (not assessable, insufficient data)
Secondary Outcome Measures
- 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
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111 |
Sponsors and Collaborators
- Fox Chase Cancer Center
Investigators
- Principal Investigator: Steven Cohen, MD, Fox Chase Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- FER-GI-002
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Cetuximab, Oxaliplatin, Capecitabine |
---|---|---|
Arm/Group Description | 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 | 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 |
Period Title: Overall Study | ||
STARTED | 12 | 11 |
COMPLETED | 12 | 11 |
NOT COMPLETED | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Cetuximab, Oxaliplatin, Capecitabine | Total |
---|---|---|---|
Arm/Group Description | 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 | 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 | Total of all reporting groups |
Overall Participants | 12 | 11 | 23 |
Age (years) [Median (Full Range) ] | |||
Median (Full Range) [years] |
59
|
58
|
59
|
Sex: Female, Male (Count of Participants) | |||
Female |
4
33.3%
|
1
9.1%
|
5
21.7%
|
Male |
8
66.7%
|
10
90.9%
|
18
78.3%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
0
0%
|
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
4
33.3%
|
0
0%
|
4
17.4%
|
White |
8
66.7%
|
11
100%
|
19
82.6%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Region of Enrollment (Count of Participants) | |||
United States |
12
100%
|
11
100%
|
23
100%
|
Outcome Measures
Title | Objective Response Rate (ORR) |
---|---|
Description | 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): 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 early death from malignant disease early death from toxicity 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) |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Cetuximab, Oxaliplatin, Capecitabine |
---|---|---|
Arm/Group Description | 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 | 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 |
Measure Participants | 11 | 11 |
Overall response |
4
33.3%
|
8
72.7%
|
Complete response |
1
8.3%
|
1
9.1%
|
Partial response |
3
25%
|
7
63.6%
|
Stable disease |
7
58.3%
|
3
27.3%
|
Title | Time to Progression (TTP) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Cetuximab, Oxaliplatin, Capecitabine |
---|---|---|
Arm/Group Description | 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 | 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 |
Measure Participants | 11 | 11 |
Median (Full Range) [months] |
8.7
|
14.4
|
Title | Overall Survival |
---|---|
Description | 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) |
Outcome Measure Data
Analysis Population Description |
---|
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/Group Title | Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Cetuximab, Oxaliplatin, Capecitabine |
---|---|---|
Arm/Group Description | 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 | 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 |
Measure Participants | 11 | 11 |
Median (Full Range) [months] |
18
|
42.5
|
Adverse Events
Time Frame | ||||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Cetuximab, Oxaliplatin, Capecitabine | ||
Arm/Group Description | 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 | 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 | ||
All Cause Mortality |
||||
Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Cetuximab, Oxaliplatin, Capecitabine | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 11/12 (91.7%) | 10/11 (90.9%) | ||
Serious Adverse Events |
||||
Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Cetuximab, Oxaliplatin, Capecitabine | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/12 (0%) | 0/11 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Cetuximab, Oxaliplatin, Capecitabine, Bevacizumab | Cetuximab, Oxaliplatin, Capecitabine | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 12/12 (100%) | 11/11 (100%) | ||
Blood and lymphatic system disorders | ||||
Neutropenia | 3/12 (25%) | 6/11 (54.5%) | ||
Infection with neutropenia | 0/12 (0%) | 1/11 (9.1%) | ||
Thrombocytopenia | 2/12 (16.7%) | 7/11 (63.6%) | ||
Gastrointestinal disorders | ||||
Constipation | 7/12 (58.3%) | 6/11 (54.5%) | ||
Diarrhea | 9/12 (75%) | 11/11 (100%) | ||
Nausea | 9/12 (75%) | 7/11 (63.6%) | ||
Vomiting | 5/12 (41.7%) | 2/11 (18.2%) | ||
General disorders | ||||
Edema | 2/12 (16.7%) | 1/11 (9.1%) | ||
Fatigue | 11/12 (91.7%) | 11/11 (100%) | ||
Pain | 9/12 (75%) | 9/11 (81.8%) | ||
Fever | 2/12 (16.7%) | 4/11 (36.4%) | ||
Immune system disorders | ||||
Hypersensitivity reaction | 4/12 (33.3%) | 1/11 (9.1%) | ||
Metabolism and nutrition disorders | ||||
Weight loss | 3/12 (25%) | 3/11 (27.3%) | ||
Hypomagnesemia | 6/12 (50%) | 6/11 (54.5%) | ||
Hyperglycemia | 6/12 (50%) | 8/11 (72.7%) | ||
Hypoalbuminemia | 2/12 (16.7%) | 5/11 (45.5%) | ||
Hypokalemia | 1/12 (8.3%) | 3/11 (27.3%) | ||
Nervous system disorders | ||||
Parasthesias | 8/12 (66.7%) | 8/11 (72.7%) | ||
Parasthesias/pain | 1/12 (8.3%) | 1/11 (9.1%) | ||
Sensory neuropathy | 5/12 (41.7%) | 6/11 (54.5%) | ||
Insomnia | 3/12 (25%) | 3/11 (27.3%) | ||
Skin and subcutaneous tissue disorders | ||||
Alopecia | 0/12 (0%) | 1/11 (9.1%) | ||
Dry/cracked skin | 3/12 (25%) | 4/11 (36.4%) | ||
Fissures | 7/12 (58.3%) | 3/11 (27.3%) | ||
Nail changes | 2/12 (16.7%) | 3/11 (27.3%) | ||
Paronychia | 5/12 (41.7%) | 7/11 (63.6%) | ||
Rash | 11/12 (91.7%) | 11/11 (100%) | ||
Hand-foot syndrome | 1/12 (8.3%) | 4/11 (36.4%) | ||
Vascular disorders | ||||
Hemmorhage | 6/12 (50%) | 4/11 (36.4%) | ||
DVT | 0/12 (0%) | 3/11 (27.3%) | ||
Hypertension | 6/12 (50%) | 2/11 (18.2%) |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Dr. Steven Cohen |
---|---|
Organization | Fox Chase Cancer Center |
Phone | 215-214-1676 |
steven.cohen@fccc.edu |
- FER-GI-002