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

Phase 2
Terminated
Conditions
Colorectal Neoplasms
Interventions
Registration Number
NCT00321100
Lead Sponsor
Fox Chase Cancer Center
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
23
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cetuximab, Oxaliplatin, Capecitabine, BevacizumabbevacizumabCetuximab 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
Cetuximab, Oxaliplatin, Capecitabine, BevacizumabcetuximabCetuximab 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
Cetuximab, Oxaliplatin, Capecitabine, BevacizumabOxaliplatinCetuximab 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
Cetuximab, Oxaliplatin, Capecitabine, BevacizumabCapecitabineCetuximab 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
Cetuximab, Oxaliplatin, CapecitabinecetuximabCetuximab 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
Primary Outcome Measures
NameTimeMethod
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 Outcome Measures
NameTimeMethod
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 SurvivalFrom 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

Trial Locations

Locations (1)

Fox Chase Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

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