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| ID | Type | Description | Link |
|---|---|---|---|
| DUMC-4951-05-7R2 | |||
| GENENTECH-DUMC-4951-05-7R2 | |||
| SANOFI-DUMC-4951-05-7R2 | |||
| ROCHE-DUMC-4951-05-7R2 | |||
| CDR0000449971 | Other Identifier | NCI |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
RATIONALE: Drugs used in chemotherapy, such as capecitabine, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving capecitabine and oxaliplatin together with bevacizumab may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving oxaliplatin and capecitabine together with bevacizumab works in treating patients with metastatic or recurrent colorectal cancer.
OBJECTIVES:
Primary
Secondary
Exploratory
OUTLINE: Patients receive oral capecitabine twice daily on days 1-5 and 8-12, oxaliplatin IV over 2 hours on day 1, and bevacizumab IV over 1-1½ hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Initial Cohort | Experimental |
| |
| Second cohort | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| bevacizumab | Biological | 10 mg/kg intravenously over 30-90 minutes on day 1 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Response Rate (Percentage of Participants With Partial or Complete Response) | Restaging scans occurred every 9 weeks from time of study drug initiation until disease progression. Disease assessment was performed and recorded according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) Guidelines. The definitions were: Complete response (CR)- Disappearance of all target lesions Partial response (PD)- At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Stable disease (SD)- Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive disease (PD) - At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions | After all subjects were evaluated for restaging which occured every 9 weeks from drug initiation until disease progression, assesed up to 24 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Progression | Disease assessment was performed and recorded according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) Guidelines. Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | From time of treatment until documented progression, assesed up to 60 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Effect on Angiogenesis Biomarkers | After study completion | |
| Effect on Wound Angiogenesis | After study completion |
DISEASE CHARACTERISTICS:
Histologically documented adenocarcinoma of the colon or rectum
No leptomeningeal or brain metastases
PATIENT CHARACTERISTICS:
ECOG performance status 0-2
Absolute neutrophil count ≥ 2,000/mm^3
Platelet count ≥ 100,000/mm^3
AST/ALT < 2.5 times upper limit of normal (ULN) (5 times ULN if known liver metastases)
Bilirubin < 1.5 times ULN
Creatinine clearance > 50 mL/min
No unstable or poorly controlled hypertension (> 150/100 mm Hg)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during study and for at least 3-4 months after study completion
No arterial or venous thrombosis (including cerebrovascular accident) within the last 3 months
No known, existing, uncontrolled coagulopathy
No clinically significant cardiac disease
No congestive heart failure
No symptomatic coronary artery disease
No cardiac arrhythmias not well controlled with medication
No myocardial infarction within the last 12 months
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to oxaliplatin, capecitabine, or bevacizumab
No history of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the patient at high risk from treatment complications
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Herbert I. Hurwitz, MD | Duke Cancer Institute | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Result | Hurwitz H, Fernando N, Yu D, et al.: A phase II study of oxaliplatin, capecitabine and bevacizumab in the treatment of metastatic colorectal cancer. [Abstract] Ann Oncol 16 (Suppl 2): A-55P, ii285, 2005. | ||
| 23634291 | Derived | Liu Y, Starr MD, Bulusu A, Pang H, Wong NS, Honeycutt W, Amara A, Hurwitz HI, Nixon AB. Correlation of angiogenic biomarker signatures with clinical outcomes in metastatic colorectal cancer patients receiving capecitabine, oxaliplatin, and bevacizumab. Cancer Med. 2013 Apr;2(2):234-42. doi: 10.1002/cam4.71. Epub 2013 Mar 6. |
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Patients were recruited between September 2003 and July 2005 in the Duke Cancer Center and Duke Oncology Network sites.
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| ID | Title | Description |
|---|---|---|
| FG000 | Initial Cohort | oxaliplatin : 85 mg/m2 intravenously over 2 hours on day 1. Capecitabine : Oral administration every 12 hours on days 1-5 and 8-12 1000 mg/m2 in initial cohort bevacizumab : 10 mg/kg intravenously over 30-90 minutes on day 1 |
| FG001 | Second Cohort | oxaliplatin : 85 mg/m2 intravenously over 2 hours on day 1. bevacizumab : 10 mg/kg intravenously over 30-90 minutes on day 1 Capecitabine : Oral administration every 12 hours on days 1-5 and 8-12 850 mg/m2 in second cohort |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Initial Cohort | oxaliplatin : 85 mg/m2 intravenously over 2 hours on day 1. Capecitabine : Oral administration every 12 hours on days 1-5 and 8-12 1000 mg/m2 in initial cohort bevacizumab : 10 mg/kg intravenously over 30-90 minutes on day 1 |
| BG001 | Second Cohort |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Response Rate (Percentage of Participants With Partial or Complete Response) | Restaging scans occurred every 9 weeks from time of study drug initiation until disease progression. Disease assessment was performed and recorded according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) Guidelines. The definitions were: Complete response (CR)- Disappearance of all target lesions Partial response (PD)- At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Stable disease (SD)- Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive disease (PD) - At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions | All subjects who had restaging scans were included in the analysis. | Posted | Number | 95% Confidence Interval | percentage of participants with response | After all subjects were evaluated for restaging which occured every 9 weeks from drug initiation until disease progression, assesed up to 24 months. |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Initial Cohort | oxaliplatin : 85 mg/m2 intravenously over 2 hours on day 1. Capecitabine : Oral administration every 12 hours on days 1-5 and 8-12 1000 mg/m2 in initial cohort bevacizumab : 10 mg/kg intravenously over 30-90 minutes on day 1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bowel Perforation | Gastrointestinal disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anorexia | Gastrointestinal disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Brant Hamel | Duke University Medical Center | 919-68-1861 | brant.hamel@duke.edu |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D003110 | Colonic Neoplasms |
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D000068258 | Bevacizumab |
| D000077150 | Oxaliplatin |
| D000069287 | Capecitabine |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| oxaliplatin | Drug | 85 mg/m2 intravenously over 2 hours on day 1. |
|
| Capecitabine | Drug | Oral administration every 12 hours on days 1-5 and 8-12 1000 mg/m2 in initial cohort |
|
| Capecitabine | Drug | Oral administration every 12 hours on days 1-5 and 8-12 850 mg/m2 in second cohort |
|
| Disease Free Survival | Disease assessment was performed and recorded according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) Guidelines. Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | From time of treatment until documented progression or death from any cause, whichever came first, assesed up to 60 months. |
| Overall Survival | Average months of survival of participants after receiving study drug. | From time of treatment until death from any cause, assesed up to 60 months. |
| Safety and Tolerability | Number of participants with adverse events | After all participants went off study drug regimine. |
oxaliplatin : 85 mg/m2 intravenously over 2 hours on day 1. bevacizumab : 10 mg/kg intravenously over 30-90 minutes on day 1 Capecitabine : Oral administration every 12 hours on days 1-5 and 8-12 850 mg/m2 in second cohort |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID | Title | Description |
|---|
| OG000 | Initial Cohort | oxaliplatin : 85 mg/m2 intravenously over 2 hours on day 1. Capecitabine : Oral administration every 12 hours on days 1-5 and 8-12 1000 mg/m2 in initial cohort bevacizumab : 10 mg/kg intravenously over 30-90 minutes on day 1 |
| OG001 | Second Cohort | oxaliplatin : 85 mg/m2 intravenously over 2 hours on day 1. bevacizumab : 10 mg/kg intravenously over 30-90 minutes on day 1 Capecitabine : Oral administration every 12 hours on days 1-5 and 8-12 850 mg/m2 in second cohort |
|
|
| Secondary | Time to Progression | Disease assessment was performed and recorded according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) Guidelines. Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Posted | Median | 95% Confidence Interval | months | From time of treatment until documented progression, assesed up to 60 months. |
|
|
|
| Secondary | Disease Free Survival | Disease assessment was performed and recorded according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) Guidelines. Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Posted | Median | 95% Confidence Interval | months | From time of treatment until documented progression or death from any cause, whichever came first, assesed up to 60 months. |
|
|
|
| Secondary | Overall Survival | Average months of survival of participants after receiving study drug. | Posted | Median | 95% Confidence Interval | months | From time of treatment until death from any cause, assesed up to 60 months. |
|
|
|
| Secondary | Safety and Tolerability | Number of participants with adverse events | Posted | Number | participants with adverse event | After all participants went off study drug regimine. |
|
|
|
| Other Pre-specified | Effect on Angiogenesis Biomarkers | Not Posted | After study completion |
| Other Pre-specified | Effect on Wound Angiogenesis | Not Posted | After study completion |
| 6 |
| 19 |
| 19 |
| 19 |
| EG001 | Second Cohort | oxaliplatin : 85 mg/m2 intravenously over 2 hours on day 1. bevacizumab : 10 mg/kg intravenously over 30-90 minutes on day 1 Capecitabine : Oral administration every 12 hours on days 1-5 and 8-12 850 mg/m2 in second cohort | 9 | 31 | 29 | 31 |
| Acute Calculus Cholecystitis | Gastrointestinal disorders |
|
| Wound Dehisence | General disorders |
|
| Congestive Heart Failure | Cardiac disorders |
|
| Seizure | Nervous system disorders |
|
| Syncope | Vascular disorders |
|
| Altered mental status | Nervous system disorders |
|
| Diarrhea | Gastrointestinal disorders |
|
| Bowel obstruction | Gastrointestinal disorders |
|
| Pain | General disorders |
|
| Vomiting | Gastrointestinal disorders |
|
| Angina | Cardiac disorders |
|
| Cellulitis | Skin and subcutaneous tissue disorders |
|
| Abdominal Cramping | Gastrointestinal disorders |
|
| Allergic reaction | Immune system disorders |
|
| Chills | General disorders |
|
| Neutropenia | Investigations |
|
| Constipation | Gastrointestinal disorders |
|
| Cough | Respiratory, thoracic and mediastinal disorders |
|
| Dehydration | Gastrointestinal disorders |
|
| Diarrhea | Gastrointestinal disorders |
|
| Edema | Respiratory, thoracic and mediastinal disorders |
|
| Fatigue | General disorders |
|
| Fever | General disorders |
|
| Flatuance | Gastrointestinal disorders |
|
| Hand-foot syndrome | Skin and subcutaneous tissue disorders |
|
| Hypertension | Vascular disorders |
|
| Hypotension | Vascular disorders |
|
| Infection | Infections and infestations |
|
| Insomnia | General disorders |
|
| Nausea | Gastrointestinal disorders |
|
| Pain | General disorders |
|
| Skin rash | Skin and subcutaneous tissue disorders |
|
| Shortness of breath | Respiratory, thoracic and mediastinal disorders |
|
| Vomiting | Gastrointestinal disorders |
|
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| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |