Combination of Cetuximab, Capecitabine, and Oxaliplatin With or Without Bevacizumab

Sponsor
Fox Chase Cancer Center (Other)
Overall Status
Terminated
CT.gov ID
NCT00321100
Collaborator
(none)
23
1
2
92.2
0.2

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

Study Type:
Interventional
Actual Enrollment :
23 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Study of the Combination of Cetuximab, Capecitabine, and Oxaliplatin With Out Without Bevacizumab as Initial Therapy for Metastatic Colorectal Cancer
Study Start Date :
Apr 12, 2006
Actual Primary Completion Date :
Apr 1, 2009
Actual Study Completion Date :
Dec 18, 2013

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:
  • Avastin
  • Drug: cetuximab
    Cetuximab 400mg/m2 IV initial dose (cycle 1 day 1 only), then 250mg/m2 IV weekly each 21 day cycle
    Other Names:
  • Erbitux
  • Drug: Oxaliplatin
    Oxaliplatin 130mg/m2 IV day 1 every 21 days
    Other Names:
  • Eloxatin
  • Drug: Capecitabine
    Capecitabine 850mg/m2 PO every 12 hours days 1-14 of each 21 day cycle
    Other Names:
  • Xeloda
  • 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:
  • Erbitux
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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

    2. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    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.
    Responsible Party:
    Fox Chase Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00321100
    Other Study ID Numbers:
    • FER-GI-002
    First Posted:
    May 3, 2006
    Last Update Posted:
    Jan 12, 2022
    Last Verified:
    Dec 1, 2021
    Keywords provided by Fox Chase Cancer Center
    Additional relevant MeSH terms:

    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

    1. Primary Outcome
    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%
    2. Secondary Outcome
    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
    3. Secondary Outcome
    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

    [Not Specified]

    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
    Email steven.cohen@fccc.edu
    Responsible Party:
    Fox Chase Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00321100
    Other Study ID Numbers:
    • FER-GI-002
    First Posted:
    May 3, 2006
    Last Update Posted:
    Jan 12, 2022
    Last Verified:
    Dec 1, 2021