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| ID | Type | Description | Link |
|---|---|---|---|
| BMS CA225302 |
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Slow accrual
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| Name | Class |
|---|---|
| Massachusetts General Hospital | OTHER |
| Beth Israel Deaconess Medical Center | OTHER |
| Brigham and Women's Hospital | OTHER |
| Bristol-Myers Squibb |
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The standard treatment for rectal cancer is to receive the chemotherapeutic drug 5-fluorouracil (5-FU) with radiation therapy before having surgery to remove the rectal cancer. This is known as neoadjuvant chemoradiotherapy. The purpose of this research study is to determine if Cetuximab improves the benefits of neoadjuvant chemoradiotherapy when given with 5-FU and radiation therapy.
The epidermal growth factor receptor (EGFR) present in normal and tumor cells is involved in signaling pathways affecting cellular growth, differentiation, proliferation and programmed cell death. Overexpression of EGFR has been associated with poorer prognosis in colorectal cancer. Cetuximab targets and blocks EGFR and has been shown to be safe and effective in treating colorectal cancer and head and neck cancers.
The primary hypothesis is that cetuximab in combination with standard 5-FU and radiation as neoadjuvant therapy would improve pathological complete response (pCR) compared to the historical rate (30% versus 10%). The regimen would be considered promising if 5 or more of 25 evaluable participants achieve pCR. The probability of observing this outcome is 0.91 and 0.10 if the true pCR rate is 30% and 10%, respectively.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cetuximab, 5-FU and Radiation | Experimental | Cetuximab: Participants first receive cetuximab at the initial dose of 400 mg/m2 intravenously (IV) administered over 120 minutes, followed by weekly infusions at 250 mg/m2 over 60 minutes. Cetuximab is given as single agent during the first 3 weeks on study and then in combination with 5-FU and radiation. Radiation: Radiation therapy given as standard of care is initiated after the 3rd dose of cetuximab with a total dose of 50.4 Gray (Gy) in 28 fractions over approximately 5.5 weeks. 5-FU: Participants receive 5-Fluorouracil (5-FU) continuous infusion through central venous access at 225 mg/m2/day given 7 days a week starting day 1 of radiation (no later than 3 days) and lasting the duration of radiation therapy. Duration of neoadjuvant therapy is estimated to be 9 weeks. Surgery follows at week 13-17. Sigmoidoscopy is performed for biopsy prior to the 1st dose and after 3rd dose of cetuximab before the initiation of radiation and/or 5-FU. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cetuximab | Drug |
|
| |
| 5-Fluorouracil |
| Measure | Description | Time Frame |
|---|---|---|
| Pathological Complete Response Rate | Pathological complete response (pCR) rate is the percentage of participants who achieve pCR defined as no evidence of tumor cells in the surgical specimen including the lymph nodes (down-staging to pathological T0, N0 after planned neoadjuvant therapy). | Disease is assessed at the time of surgery which in this study cohort occurred up to 24 weeks from date of registration. |
| Measure | Description | Time Frame |
|---|---|---|
| Local Recurrence Rate | Local recurrence rate is the percentage of participants experiencing recurrence within the pelvis. | CT scans for surveillance recommended yearly x 3 years from date of surgery with additional scanning at discretion of treating oncologist. Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years. |
| Measure | Description | Time Frame |
|---|---|---|
| 1-Year Disease-Free Survival Rate | Disease-Free Survival Rate is the percentage of participants remaining alive without disease progression. | CT scans for surveillance recommended yearly x 3 years from date of surgery with additional scanning at discretion of treating oncologist. Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jeffrey Meyerhardt, MD, MPH | Dana-Farber Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States | ||
| Dana-Farber Cancer Institute |
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Participants were enrolled from May 2008 through July 2012.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cetuximab With Standard 5-FU and Radiation | Cetuximab: Participants first receive cetuximab at the initial dose of 400 mg/m2 intravenously (IV) administered over 120 minutes, followed by weekly infusions at 250 mg/m2 over 60 minutes. Cetuximab is given as single agent during the first 3 weeks on study and then in combination with 5-FU and radiation. Radiation: Radiation therapy given as standard of care is initiated after the 3rd dose of cetuximab with a total dose of 50.4 Gray (Gy) in 28 fractions over approximately 5.5 weeks. 5-FU: Participants receive 5-Fluorouracil (5-FU) continuous infusion through central venous access at 225 mg/m2/day given 7 days a week starting day 1 of radiation (no later than 3 days) and lasting the duration of radiation therapy. Duration of neoadjuvant therapy is estimated to be 9 weeks. Surgery follows at week 13-17. Sigmoidoscopy is performed for biopsy prior to the 1st dose and after 3rd dose of cetuximab before the initiation of radiation and/or 5-FU. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | Cetuximab With Standard 5-FU and Radiation | Cetuximab: Participants first receive cetuximab at the initial dose of 400 mg/m2 intravenously (IV) administered over 120 minutes, followed by weekly infusions at 250 mg/m2 over 60 minutes. Cetuximab is given as single agent during the first 3 weeks on study and then in combination with 5-FU and radiation. Radiation: Radiation therapy given as standard of care is initiated after the 3rd dose of cetuximab with a total dose of 50.4 Gray (Gy) in 28 fractions over approximately 5.5 weeks. 5-FU: Participants receive 5-Fluorouracil (5-FU) continuous infusion through central venous access at 225 mg/m2/day given 7 days a week starting day 1 of radiation (no later than 3 days) and lasting the duration of radiation therapy. Duration of neoadjuvant therapy is estimated to be 9 weeks. Surgery follows at week 13-17. Sigmoidoscopy is performed for biopsy prior to the 1st dose and after 3rd dose of cetuximab before the initiation of radiation and/or 5-FU. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Pathological Complete Response Rate | Pathological complete response (pCR) rate is the percentage of participants who achieve pCR defined as no evidence of tumor cells in the surgical specimen including the lymph nodes (down-staging to pathological T0, N0 after planned neoadjuvant therapy). | The analysis dataset is comprised of all enrolled patients. | Posted | Number | 90% Confidence Interval | percentage of participants | Disease is assessed at the time of surgery which in this study cohort occurred up to 24 weeks from date of registration. |
|
Adverse events (AEs) are assessed through the time of surgery which in this study cohort occurred up to 24 weeks from date of registration.
Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term.
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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 | Cetuximab With Standard 5-FU and Radiation | Patients with stage II/III rectal cancer who have received cetuximab with standard 5-FU and radiation as neoadjuvant therapy. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Proctitis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
This study was terminated early due to weak accrual.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jeffrey Meyerhardt, MD, MPH | Dana-Farber Cancer Institute | 617-632-6855 | Jeffrey_Meyerhardt@dfci.harvard.edu |
Not provided
| ID | Term |
|---|---|
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
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| ID | Term |
|---|---|
| D000068818 | Cetuximab |
| D005472 | Fluorouracil |
| D011827 | Radiation |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| INDUSTRY |
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| Drug |
|
|
| Radiation | Radiation |
|
|
| Complete Resection Rate | Complete resection rate is the percentage of participants having all gross disease removed by the surgeon at the time of operation. | Disease is assessed at the time of surgery which in this study cohort occurred up to 24 weeks from date of registration. |
| Distant Recurrence Rate | Distant recurrence rate is the percentage of participants experiencing recurrence outside the pelvis. | CT scans for surveillance recommended yearly x 3 years from date of surgery with additional scanning at discretion of treating oncologist. Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years. |
| Incidence of Grade 4 Treatment-Related Toxicity | All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3) as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation. | Disease is assessed through the time of surgery which in this study cohort occurred up to 24 weeks from date of registration. |
| 1-Year Overall Survival Rate | 1-year overall survival is the percentage of participants remaining alive 1 year from study entry. | Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years. |
| Boston |
| Massachusetts |
| 02115 |
| United States |
| South Shore Hospital | Weymouth | Massachusetts | United States |
| Vanderbilt Medical Center | Nashville | Tennessee | United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Local Recurrence Rate | Local recurrence rate is the percentage of participants experiencing recurrence within the pelvis. | The analysis dataset is comprised of all enrolled patients. | Posted | Number | 90% Confidence Interval | percentage of participants | CT scans for surveillance recommended yearly x 3 years from date of surgery with additional scanning at discretion of treating oncologist. Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years. |
|
|
|
| Secondary | Complete Resection Rate | Complete resection rate is the percentage of participants having all gross disease removed by the surgeon at the time of operation. | The analysis dataset is comprised of all enrolled patients. | Posted | Number | 90% Confidence Interval | percentage of participants | Disease is assessed at the time of surgery which in this study cohort occurred up to 24 weeks from date of registration. |
|
|
|
| Secondary | Distant Recurrence Rate | Distant recurrence rate is the percentage of participants experiencing recurrence outside the pelvis. | The analysis dataset is comprised of all enrolled patients. | Posted | Number | 90% Confidence Interval | percentage of participants | CT scans for surveillance recommended yearly x 3 years from date of surgery with additional scanning at discretion of treating oncologist. Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years. |
|
|
|
| Secondary | Incidence of Grade 4 Treatment-Related Toxicity | All grade 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on NCI Common Toxicity Criteria for Adverse Events version 3 (CTCAEv3) as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade 4 AE of any type during the time of observation. | The analysis dataset is comprised of all enrolled patients. | Posted | Count of Participants | Participants | Disease is assessed through the time of surgery which in this study cohort occurred up to 24 weeks from date of registration. |
|
|
|
| Secondary | 1-Year Overall Survival Rate | 1-year overall survival is the percentage of participants remaining alive 1 year from study entry. | Posted | Number | 90% Confidence Interval | percentage of participants | Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years. |
|
|
|
| Other Pre-specified | 1-Year Disease-Free Survival Rate | Disease-Free Survival Rate is the percentage of participants remaining alive without disease progression. | The analysis dataset is comprised of all enrolled patients. | Posted | Number | 90% Confidence Interval | percentage of participants | CT scans for surveillance recommended yearly x 3 years from date of surgery with additional scanning at discretion of treating oncologist. Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years. |
|
|
|
| 0 |
| 13 |
| 6 |
| 13 |
| 13 |
| 13 |
| Rectum, pain | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cytokine release syndrome | Immune system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Lymphopenia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Rash: acne/acneiform | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Ulceration | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemoglobin | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hearing-other | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Diarrhea w/o prior colostomy | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhoids | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Muco/stomatitis by exam, oral cavity | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Muco/stomatitis (symptom) oral cavity | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Proctitis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Oral cavity, hemorrhage | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rectum, hemorrhage | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Abdomen, pain | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rectum, pain | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fever w/o neutropenia | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Edema limb | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain NOS | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infection Gr0-2 neut, middle ear | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection Gr0-2 neut, sinus | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection Gr0-2 neut, urinary tract | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Burn | Injury, poisoning and procedural complications | CTCAE (3.0) | Systematic Assessment |
|
| Chemoradiation dermatitis | Injury, poisoning and procedural complications | CTCAE (3.0) | Systematic Assessment |
|
| Radiation dermatitis | Injury, poisoning and procedural complications | CTCAE (3.0) | Systematic Assessment |
|
| Leukocytes | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Lymphopenia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Neutrophils | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Platelets | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Weight loss | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Alkaline phosphatase | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| ALT, SGPT | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| AST, SGOT | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bicarbonate | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypernatremia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Back, pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Muscle, pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Taste disturbance | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy CN XII tongue | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy-sensory | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Head/headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nose, hemorrhage | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pulmonary/Upper Respiratory-other | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sweating | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nail changes | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash/desquamation | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash: acne/acneiform | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hand-foot reaction | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Skin-other | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Thrombosis/thrombus/embolism | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
Not provided
Not provided
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal 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 |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D055585 | Physical Phenomena |