Cancer of the Rectum, Colorectal Cancer, Rectal Cancer
Conditions
Keywords
Rectal Cancer, Cancer of the Rectum, Colorectal Cancer, Bevacizumab
Brief summary
This phase II trial will investigate the combination of adjuvant 5-fluorouracil, radiation, and bevacizumab in patients with stage II and III rectal cancer, followed by FOLFOX6 and bevacizumab. Fluorouracil (FU) has proven to be an effective and safe regimen in the treatment of stage II and III rectal cancer. Recent evidence has proven fluorouracil/leucovorin (FL) in combination with bevacizumab is superior to FL alone and when combined with irinotecan is superior to (irinotecan plus fluorouracil/leucovorin (IFL) alone. This trial will be one of the first clinical trials to evaluate a combination of targeted therapy, radiation, and chemotherapy in the adjuvant treatment of a common solid tumor.
Detailed description
All eligible patients will receive combined modality treatment initially. Systemic treatment will begin 4-6 weeks after completion of the Combined Modality portion and will complete 4 cycles of a 4 week regimen. Patients with no evidence of disease following systemic therapy may continue single agent bevacizumab for up to one year. After all treatment is completed, patients will be re-evaluated with imaging to establish a new baseline. Patients will be re-evaluated thereafter for up to a total of 5 years. Combined Modality Treatment: * bevacizumab 5mg/kg IV infusion days 1, 15, and 29 * fluorouracil 225mg/m2 IV continuous infusion days 1-42 * radiation 1.8 Gy/day or 28 fractions weeks 1-6 Systemic Treatment: * 5-fluorouracil 400 mg/m2 bolus * 5-fluorouracil 2400 mg/m2 over 46 hours days 1 and 15 * leucovorin 350 mg prior to FU on days 1 and 15 * oxaliplatin 85 mg/m2 days 1 and 15 * bevacizumab 5 mg/kg days 1 and 15
Interventions
DRUG5-Fluorouracil
Combined Modality Treatment: fluorouracil 225mg/m2 IV continuous infusion days 1-42 Systemic Treatment: 5-fluorouracil 400 mg/m2 bolus 5-fluorouracil 2400 mg/m2 over 46 hours days 1 and 15
DRUGBevacizumab
Combined Modality Treatment: bevacizumab 5mg/kg IV infusion days 1, 15, and 29 Systemic Treatment: bevacizumab 5 mg/kg days 1 and 15
PROCEDURERadiation Therapy
radiation 1.8 Gy/day or 28 fractions weeks 1-6
DRUGOxaliplatin
Systemic Treatment: oxaliplatin 85 mg/m2 days 1 and 15
DRUGLeucovorin
Systemic Treatment: leucovorin 350 mg prior to FU on days 1 and 15
Sponsors
Genentech, Inc.
SCRI Development Innovations, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed Stage I or II rectal cancer * Patients must be candidates for preoperative or adjuvant chemoradiation. * Patients enrolling in the adjuvant chemoradiation cohort must have undergone surgical resection of the primary rectal tumor between 28 and 56 days (i.e., 4-8 weeks) prior to study treatment. * ECOG performance status 0-1 * Adequate bone marrow, liver, and kidney function * At least 18 years of age * Able to give written informed consent
Exclusion criteria
* Treatment with prior chemotherapy or radiation for rectal cancer * History of myocardial infarction * Uncontrolled hypertension, unstable angina, congestive heart failure, serious cardiac arrhythmia requiring medication or peripheral vascular disease * History of stroke within 6 months * History of abdominal fistula, gastrointestinal perforation, or intrabdominal abscess within 6 months * Symptomatic sensory or peripheral neuropathy * Prior treatment with anti-angiogenic agents * Prior malignancy in the past 5 years * Active infections or serious underlying medical condition * Major surgery less than 28 days prior * Women who are pregnant or lactating * Thrombolytic therapy within 10 days of starting bevacizumab * PEG tube, G-tube, or external biliary stents * Proteinuria * Non healing wound, ulcer or fracture * History of bleeding diathesis or coagulopathy * Hemoptysis * Participation in another experimental trial within 28 days * Uncontrolled anticoagulant therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-Free Survival (DFS), The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment | 24 months | The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | 24 months | Overall Survival (OS) is defined ad the Length of time, in months, that patients were alive from their first date of protocol treatment until death. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Preoperative 5FU/Radiation/Bevacizumab Each patient enrolled in the preoperative cohort received 5-fluorouracil (5-FU) 225 mg/m2 as a continuous infusion (IVCI) on days 1-42 through a portable infusion pump and central venous catheter. Bevacizumab 5 mg/kg was administered intravenously (IV) on days 1 and 15. Additionally these patients received radiation therapy to 50.4 Gy (1.8 Gy/day or 28 fractions) Monday through Friday during weeks 1-6.
At least 8 weeks after surgery, patients in cohort A began 4 months of chemotherapy and bevacizumab. This adjuvant treatment consisted of 5-FU 400 mg/m2 IV bolus over 2-4 minutes followed by 2400 mg/m2 IVCI over 46 hours, leucovorin 350 mg as a 2-hour infusion, oxaliplatin 85 mg/m2 IV (modified FOLFOX6) and bevacizumab 5 mg/kg IV all on days 1 and 15 of each cycle. | 35 |
| Postoperative 5FU/Radiation/Bevacizumab All patients enrolled in cohort B received 5-fluorouracil (5-FU) 225 mg/m2 IVCI on days 1-42. Bevacizumab was administered at 5 mg/kg IV on day 1 every 2 weeks. These patients also received radiation to 50.4 Gy (1.8 Gy/day or 28 fractions)Monday through Friday during weeks 1-6.
Six weeks after the completion of adjuvant 5-FU/radiation, patients began treatment with 5-FU 400 mg/m2 IV bolus over 2-4 minutes followed by 2400 mg/m2 IVCI over 46 hours, leucovorin 350 mg as a 2-hour infusion, oxaliplatin 85 mg/m2 IV (modified FOLFOX6) and bevacizumab 5 mg/kg IV all on days 1 and 15 of each cycle. | 31 |
| Total | 66 |
Baseline characteristics
| Characteristic | Preoperative 5FU/Radiation/Bevacizumab | Postoperative 5FU/Radiation/Bevacizumab | Total |
|---|---|---|---|
| Age, Continuous | 57 years | 56 years | 57 years |
| Region of Enrollment United States | 35 participants | 31 participants | 66 participants |
| Sex: Female, Male Female | 9 Participants | 16 Participants | 25 Participants |
| Sex: Female, Male Male | 26 Participants | 15 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 35 | 31 / 31 |
| serious Total, serious adverse events | 18 / 35 | 15 / 31 |
Outcome results
Primary
Disease-Free Survival (DFS), The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment
The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment
Time frame: 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Preoperative 5FU/Radiation/Bevacizumab | Disease-Free Survival (DFS), The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment | 85 percentage of participants |
| Postoperative 5FU/Radiation/Bevacizumab | Disease-Free Survival (DFS), The Proportion of Patients Predicted to be Alive Without Evidence of Disease Recurrence 24 Months After Completion of Protocol Treatment | 97 percentage of participants |
Secondary
Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Overall Survival (OS) is defined ad the Length of time, in months, that patients were alive from their first date of protocol treatment until death.
Time frame: 24 months
Population: The median survival was not reached for either of the cohorts
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Preoperative 5FU/Radiation/Bevacizumab | Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | NA months |
| Postoperative 5FU/Radiation/Bevacizumab | Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | NA months |