Colorectal CancerPhase 2NCT00831181
Neo-adjuvant Chemoradiation With Oxaliplatin/5-FU in Rectal Cancer
A Phase 2 study testing 5-FU, Oxaliplatin and leucovorin in people with Colorectal Cancer, run by Beth Israel Medical Center at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- 5-FU, Oxaliplatin and leucovorin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2004to Nov 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven adenocarcinoma of the rectum with no distant metastases.
- T3-4N0M0, TanyN1-3M0 assessed by clinical exam, TRUS, MRI and CT
- The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 centimeters of the anal verge by protoscopic examination.
- No prior chemotherapy or pelvic irradiation.
- ECOG performance status 0-1
- Age 18 to 70 years
- ANC >= 1500/mm3 and platelets >= 100,000/mm3
- Serum creatinine <= 1.5 x ULN; bilirubin <= 1.5 x ULN; ALT<= 2.5 x ULN
Who cannot join
- Pregnant or lactating females; patients not practicing active contraception while sexually active.
- No other serious medical condition
- A psychiatric disorder that would prohibit the subject from participating fully.
- Peripheral neuropathy > grade 1
- History within the past 5 years of a cancer diagnosis except for non-melanomatous skin cancers or in situ cervix carcinoma.
- HIV positive patients
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Beth Israel Medical Center - Philipps Ambulatory Care Center
New York, New York, 10003
St. Luke's-Roosevelt Hospital Center - Roosevelt Division
New York, New York, 10019
About this study
Official title: A Phase II Open-labeled, Prospective Study to Determine the Efficacy of Preoperative Chemoradiation With Oxaliplatin/5-FU in Locally Advanced Rectal Cancer Followed by Total Mesorectal Excision and FOLFOX6
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.
Read the detailed description
OBJECTIVES:
Primary
- To assess the complete pathologic response rate in patients with rectal cancer treated with radiation, modified neoadjuvant FOLFOX 6 chemotherapy followed by total mesorectal excision and adjuvant modified FOLFOX 6 chemotherapy.
Secondary
- To observe the overall pathologic response rate in these patients.
- To correlate pathologic staging with preoperative ultrasound and pelvic MRI staging.
- To assess toxic side effects of these regimens in these patients.
- To assess patterns of disease relapse, disease-free survival outcomes, and overall survival outcomes of these patients.
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.
- Conditions
- Colorectal Cancer
- Being tested
- 5-FU, Oxaliplatin, leucovorin, mesorectal excision
- Keywords
- stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum
- Medical subject headings
- Colorectal Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-FUDrug
Also called fluorouracil
5-FU: continuous infusion via portable pump during all RT (approximately 33 days)
OxaliplatinDrug
Also called Eloxatin
Oxaliplatin: 50mg/m2 weekly dosing during RT (Day 1)
leucovorinDrug
Also called Folinic Acid
Folinic Acid (Leucovorin): 400 mg/m2; 2-hour IV infusion simultaneously with oxaliplatin
mesorectal excisionProcedure or surgery
mesorectal excision
| Study group | Role | What they receive |
|---|---|---|
| Preoperative Chemoradiation | Experimental | Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and 5-FU / leucovorin (FOLFOX 6) Receives: Drug: 5-FU; Drug: Oxaliplatin; Drug: leucovorin; Procedure: mesorectal excision |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, an average of 3.5 months
Secondary outcomes (7)
Treatment Toxicity
Toxicity was assessed weekly during neoadjuvant chemotherapy and radiation therapy, bi-weekly during adjuvant FOLFOX therapy.
Measured: Weekly during chemoradiation treatment (3 months). Bi-weekly during adjuvant FOLFOX therapy (3.5 months).
Complete Resectability Rates
Complete resectability rates assessed by circumferential margin.
Measured: 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
Measured: median follow-up 22 months post-TME
Disease-free Survival
Measured: median 22 months follow-up
Overall Survival
Measured: median follow-up 22 months
Patterns of Disease Failure, Including Local Recurrence and Distant Metastasis Assessed by CT Scan
Measured: 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.
Measured: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, 3 months after beginning of chemoradiation treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2009 (estimated)
- Study startJul 2004
- Primary completionNov 2009
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter Kozuch, MD, Principal investigator, Beth Israel Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00831181
- Sponsor's protocol ID
- CDR0000633360
- Other IDs
- BIMCP-OX-08-006, AVENTIS-BIMCP-OX-08-006
- Status last verified
- Feb 2018
- First submitted
- 27 Jan 2009
- Last updated
- 20 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Open-labeled, Prospective Study to Determine the Efficacy of Preoperative Chemoradiation With Oxaliplatin/5-FU in Locally Advanced Rectal Cancer Followed by Total Mesorectal Excision and FOLFOX6
- ClinicalTrials.gov ID
- NCT00831181
- Acronym / sponsor ID
- CDR0000633360
- Conditions
- Colorectal Cancer
- Keywords
- stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Beth Israel Medical CenterUniversity, hospital or other
- Study start
- Jul 2004
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 28 Jan 2009 (estimated)
- Results
- Posted 20 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary
- To assess the complete pathologic response rate in patients with rectal cancer treated with radiation, modified neoadjuvant FOLFOX 6 chemotherapy followed by total mesorectal excision and adjuvant modified FOLFOX 6 chemotherapy.
Secondary
- To observe the overall pathologic response rate in these patients.
- To correlate pathologic staging with preoperative ultrasound and pelvic MRI staging.
- To assess toxic side effects of these regimens in these patients.
- To assess patterns of disease relapse, disease-free survival outcomes, and overall survival outcomes of these patients.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Preoperative Chemoradiation | Experimental | Drug: 5-FU, Drug: Oxaliplatin, Drug: leucovorin, Procedure: mesorectal excisionPreoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and 5-FU / leucovorin (FOLFOX 6) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically proven adenocarcinoma of the rectum with no distant metastases.
- T3-4N0M0, TanyN1-3M0 assessed by clinical exam, TRUS, MRI and CT
- The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 centimeters of the anal verge by protoscopic examination.
- No prior chemotherapy or pelvic irradiation.
- ECOG performance status 0-1
Key exclusion criteria (6 listed)
- Pregnant or lactating females; patients not practicing active contraception while sexually active.
- No other serious medical condition
- A psychiatric disorder that would prohibit the subject from participating fully.
- Peripheral neuropathy > grade 1
- History within the past 5 years of a cancer diagnosis except for non-melanomatous skin cancers or in situ cervix carcinoma.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5-FUAlso: fluorouracil5-FU: continuous infusion via portable pump during all RT (approximately 33 days) | Drug | Preoperative Chemoradiation |
| OxaliplatinAlso: EloxatinOxaliplatin: 50mg/m2 weekly dosing during RT (Day 1) | Drug | Preoperative Chemoradiation |
| leucovorinAlso: Folinic AcidFolinic Acid (Leucovorin): 400 mg/m2; 2-hour IV infusion simultaneously with oxaliplatin | Drug | Preoperative Chemoradiation |
| mesorectal excisionmesorectal excision | Procedure or surgery | Preoperative Chemoradiation |
Primary outcome
Pathologic Response and Complete Response
Time frame: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, an average of 3.5 months
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.
7 secondary outcomes
Treatment Toxicity
Time frame: Weekly during chemoradiation treatment (3 months). Bi-weekly during adjuvant FOLFOX therapy (3.5 months).
Complete Resectability Rates
Time frame: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, 3 months after beginning of chemoradiation treatment.
Local Regional Control
Time frame: median follow-up 22 months post-TME
Disease-free Survival
Time frame: median 22 months follow-up
Overall Survival
Time frame: median follow-up 22 months
Patterns of Disease Failure, Including Local Recurrence and Distant Metastasis Assessed by CT Scan
Time frame: median follow-up 22 months
Number of Participants With Comparison of Preoperative Stage With Post-treatment Pathologic Stage
Time frame: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, 3 months after beginning of chemoradiation treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Kozuch, MD principal investigator
Beth Israel Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 5-FU, Oxaliplatin and leucovorin in people with Colorectal Cancer, run by Beth Israel Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic Response and Complete Response (time frame: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, an average of 3.5 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2018.