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| ID | Type | Description | Link |
|---|---|---|---|
| BIMCP-OX-08-006 | Registry Identifier | BIMCP-OX-08-006 | |
| AVENTIS-BIMCP-OX-08-006 | Other Grant/Funding Number | AVENTIS-BIMCP-OX-08-006 |
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RATIONALE: 5FU based neoadjuvant chemoradiation (nCRT) is the standard of care for Stage II/III rectal cancer. Pathologic complete response (pCR) and downstaging have been associated with improved outcomes. The addition of oxaliplatin (OXA) to neoadjuvant therapy may reduce distant disease recurrence. Adjuvant treatment with OXA for rectal cancer has been motivated by benefits demonstrated in stage III colon cancer.
Objective: To determine the feasibility, toxicity, and efficacy of preoperative OXA/5FU and RT followed by total mesorectal excision (TME) and adjuvant
PURPOSE: This phase II trial is studying the side effects and how well giving neo-adjuvant combination chemotherapy with radiation works in treating patients undergoing surgery for rectal cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE:
Patients with stage II/III rectal cancer were treated with OXA 60mg/m2 weekly continuous infusion 5FU of 225 mg/m2/d d1-5 with pelvic RT of 1.8Gy/d for 28 doses. Adjuvant therapy consisted of 6 cycles of biweekly FOLFOX6.
Surgery: Patients undergo total mesorectal excision by anterior resection or an abdominal perineal resection within 4 weeks after completion of neoadjuvant therapy.
Adjuvant therapy: Within 4 weeks after surgery, patients receive modified FOLFOX 6 chemotherapy comprising oxaliplatin and leucovorin calcium IV over 2 hours on day 1 and continuous fluorouracil IV over 46 hours on days 1-2. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Patients complete quality of life assessment questionnaires at baseline and at each follow-up visit.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and annually thereafter.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Preoperative Chemoradiation | Experimental | Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and 5-FU / leucovorin (FOLFOX 6) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 5-FU | Drug | 5-FU: continuous infusion via portable pump during all RT (approximately 33 days) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pathologic Response and Complete Response | Pathologic Response and Complete Response to preoperative therapy will be determined at the time of surgical resection. All grossly visible areas of ulceration and/or induration with be measured and submitted for histological evaluation. The unit of measure is the tumor response rate to preoperative chemoradiation. Pathologic complete response (pCR) is defined as no evidence of invasive tumor cells on pathologic examination of the primary rectal cancer. Tumor regression grade (TRG) will be quantitated into five grades: TRG 1 (complete regression) -absence of residual cancer and fibrosis extending from the site of original tumor through the layers of the rectal wall. TRG 2 characterized by the presence of rare residual cancer cells scattered through the fibrosis. TRG 3 characterized by an increase in the number of residual cancer cells, but fibrosis still predominant. TRG 4 -residual cancer outgrowing fibrosis. TRG 5 characterized by absence of regressive changes. | Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, an average of 3.5 months |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment Toxicity | Toxicity was assessed weekly during neoadjuvant chemotherapy and radiation therapy, bi-weekly during adjuvant FOLFOX therapy. | Weekly during chemoradiation treatment (3 months). Bi-weekly during adjuvant FOLFOX therapy (3.5 months). |
| Complete Resectability Rates |
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Inclusion Criteria
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Peter Kozuch, MD | Beth Israel Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beth Israel Medical Center - Philipps Ambulatory Care Center | New York | New York | 10003 | United States | ||
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Subjects were recruited from 2004-2009 from the oncology practice at Beth Israel and Roosevelt Hospitals.
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| ID | Title | Description |
|---|---|---|
| FG000 | Oxaliplatin/5-FU Followed by Mesorectal Excision and FOLFOX 6 | Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6: Preoperative therapy: Oxaliplatin 60 mg/m2 weekly dosing during radiation with continuous infusion 5-FU 225 mg/m2/d Monday through Friday for a total of 96 hours per week each week of radiation (approximately 6-7 weeks). Radiation dose will be 50-54Gy with possible intraoperative (IORT) radiation (10-12Gy). Surgery: Total Mesorectal Excision Postoperative therapy: FOLFOX6 every 2 weeks for 6 cycles (3 months) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Chemoradiation,Surgery, Chemotherapy | Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6 |
| 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 | Pathologic Response and Complete Response | Pathologic Response and Complete Response to preoperative therapy will be determined at the time of surgical resection. All grossly visible areas of ulceration and/or induration with be measured and submitted for histological evaluation. The unit of measure is the tumor response rate to preoperative chemoradiation. Pathologic complete response (pCR) is defined as no evidence of invasive tumor cells on pathologic examination of the primary rectal cancer. Tumor regression grade (TRG) will be quantitated into five grades: TRG 1 (complete regression) -absence of residual cancer and fibrosis extending from the site of original tumor through the layers of the rectal wall. TRG 2 characterized by the presence of rare residual cancer cells scattered through the fibrosis. TRG 3 characterized by an increase in the number of residual cancer cells, but fibrosis still predominant. TRG 4 -residual cancer outgrowing fibrosis. TRG 5 characterized by absence of regressive changes. | Number of subjects undergoing TME | Posted | Number | Participants | Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, an average of 3.5 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 | Chemoradiation,Surgery, Chemotherapy | Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| peripheral neuropathy | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Peter Kozuch | Beth Israel Medical Center | 212 844-8282 | pkozuch@chpnet.org |
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| ID | Term |
|---|---|
| D015179 | Colorectal 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 |
|---|---|
| D005472 | Fluorouracil |
| D000077150 | Oxaliplatin |
| D002955 | Leucovorin |
| ID | Term |
|---|---|
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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| Oxaliplatin | Drug | Oxaliplatin: 50mg/m2 weekly dosing during RT (Day 1) |
|
|
| leucovorin | Drug | Folinic Acid (Leucovorin): 400 mg/m2; 2-hour IV infusion simultaneously with oxaliplatin |
|
|
| mesorectal excision | Procedure | mesorectal excision |
|
Complete resectability rates assessed by circumferential margin. |
| Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, 3 months after beginning of chemoradiation treatment. |
| Local Regional Control | subjects were followed for median of 22 months post-surgery | median follow-up 22 months post-TME |
| Disease-free Survival | median 22 months follow-up |
| Overall Survival | median follow-up 22 months |
| Patterns of Disease Failure, Including Local Recurrence and Distant Metastasis Assessed by CT Scan | median follow-up 22 months |
| Number of Participants With Comparison of Preoperative Stage With Post-treatment Pathologic Stage | Thin-section high resolution pelvic MRI was used to image the tumor prior to chemoradiation and repeated prior to surgery, and then compared to post-treatment pathological stage. | Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, 3 months after beginning of chemoradiation treatment. |
| St. Luke's-Roosevelt Hospital Center - Roosevelt Division |
| New York |
| New York |
| 10019 |
| United States |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID | Title | Description |
|---|
| OG000 | Chemoradiation,Surgery, Chemotherapy | Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6 |
|
|
| Secondary | Treatment Toxicity | Toxicity was assessed weekly during neoadjuvant chemotherapy and radiation therapy, bi-weekly during adjuvant FOLFOX therapy. | According to the citation J Clin Oncol 28,2010 (suppl; abstract e14128): acute grade 3-4 toxicities occurred in 16 patients, mainly hypersensitivity reactions and OXA associated peripheral neuropathy. | Posted | Number | patients | Weekly during chemoradiation treatment (3 months). Bi-weekly during adjuvant FOLFOX therapy (3.5 months). |
|
|
|
| Secondary | Complete Resectability Rates | Complete resectability rates assessed by circumferential margin. | Out of the 27 patients enrolled, a total 23 underwent TME. | Posted | Number | patient | Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, 3 months after beginning of chemoradiation treatment. |
|
|
|
| Secondary | Local Regional Control | subjects were followed for median of 22 months post-surgery | Out of the 27 patients enrolled, a total 23 underwent TME and were assessed for local regional control. | Posted | Number | patient | median follow-up 22 months post-TME |
|
|
|
| Secondary | Disease-free Survival | Out of the 27 patients enrolled, a total 23 underwent TME and were assessed for disease-free survival. | Posted | Number | participants | median 22 months follow-up |
|
|
|
| Secondary | Overall Survival | Patients who completed treatment | Posted | Number | participants | median follow-up 22 months |
|
|
|
| Secondary | Patterns of Disease Failure, Including Local Recurrence and Distant Metastasis Assessed by CT Scan | Out of the 27 patients enrolled, a total 23 underwent TME and were assessed for patterns of disease failure. | Posted | Number | patients | median follow-up 22 months |
|
|
|
| Secondary | Number of Participants With Comparison of Preoperative Stage With Post-treatment Pathologic Stage | Thin-section high resolution pelvic MRI was used to image the tumor prior to chemoradiation and repeated prior to surgery, and then compared to post-treatment pathological stage. | Out of the 27 patients enrolled, a total 23 underwent TME. These 23 patients were included for comparison of preoperative stage and post-treatment pathologic stage. | Posted | Number | patient | Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, 3 months after beginning of chemoradiation treatment. |
|
|
|
| 16 |
| 27 |
| 0 |
| 27 |
| oxaliplatin intolerance | Immune system disorders | Systematic Assessment |
|
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| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D006571 |
| Heterocyclic Compounds |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |