Rectal NeoplasmsPhase 2NCT00832299
Neo-Adjuvant FOLFOX for Rectal Carcinoma
A Phase 2 study testing FOLFOX and total mesorectal excision (TME) in people with Rectal Neoplasms, run by Beth Israel Medical Center at 2 sites in United States.
Trial summary
A Phase II open- labeled, prospective study to determine the efficacy of pre-operative chemotherapy with six cycles of modified FOLFOX 6 followed by total mesorectal excision (TME) followed by an additional six cycles of FOLFOX 6. The objectives of this study are the following: 1. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Rectal Neoplasms
- What is being tested?
- FOLFOX and total mesorectal excision (TME)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2009to Aug 2011
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must consent to participate in the study and must have signed and dated an IRB-approved consent form conforming to federal and institutional guidelines
- Patient must have histologically proven adenocarcinoma of the rectum with no distant metastases
- Tumor stage must be T3N0M0, T1-3 N1M0 assessed by clinical exam, TRUS, MRI and CT. Pre-operative evidence of T4, N2 or distal lesions (0-6 cm from anal verge) should receive preoperative RT and not be offered this protocol. Any pT4, pN2 or CRM+ patients should be offered postoperative radiation
- The proximal border of the tumor must be at or below 12 centimeters of the anal verge by proctoscopic examination
- The distal border of the tumor must be at or above 6 cm from the anal verge on preoperative proctoscopy with the patient in the left lateral decubitus position
- Patient must have had no prior chemotherapy or pelvic irradiation
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- Karnofsky performance status of 60 or greater; ECOG performance status 0-1
- Patients should be age 18 years and older
- Pretreatment absolute neutrophil count >= 1000/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
- Patients can not be receiving any other investigational agents
- Patients with known metastases will be excluded from the study
- Patients with history of significant neuropathy or current symptoms of neuropathy
- Patients with history of allergic reactions attributed to compounds of similar chemical or biologic composition to oxaliplatin or 5-FU or leucovorin
- Patients with uncontrolled intercurrent illness not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because oxaliplatin and 5-FU/LV are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with oxaliplatin and 5-FU/LV, breastfeeding should be discontinued if the mother is treated with these agents
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- HIV positive patients
- Patients with serious comorbid disease which prevents delivery of full treatment including psychiatric disorders and cardiopulmonary disease
- No history within the past 5 years of a cancer diagnosis except for non-melanomatous skin cancers or in situ cervix carcinoma
- Patients with clinically significant peripheral neuropathy at the time of start of treatment (defined in the NCI Common Terminology Criteria for Adverse Events Version 3[CTCAE v3.0] as grade 2 or greater neurosensory or neuromotor toxicity
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Beth Israel Medical Center
New York, New York, 10003
St. Luke's Roosevelt Hospital Center
New York, New York, 10019
About this study
Official title: A Phase II Open- Labeled, Prospective Study to Determine the Efficacy of Pre- Operative Chemotherapy With Six Cycles of Modified FOLFOX 6 Followed by Total Mesorectal Excision (TME) Followed by an Additional Six Cycles of FOLFOX 6
A Phase II open- labeled, prospective study to determine the efficacy of pre-operative chemotherapy with six cycles of modified FOLFOX 6 followed by total mesorectal excision (TME) followed by an additional six cycles of FOLFOX 6.
The objectives of this study are the following:
- The primary endpoint of this trial is pathologic complete response (response rate).
- Secondary endpoints will include observation of overall pathologic response rate, correlation of pathologic staging with pre-operative ultrasound and pelvic MRI staging, as well as observation of toxic side effects, patterns of disease relapse, disease-free survival outcomes and overall survival outcomes.
Read the detailed description
Principal Investigator: Peter Kozuch, M.D.
Sites: BIMC/SLRHC
Introduction
A Phase II open- labeled, prospective study to determine the efficacy of pre-operative chemotherapy with six cycles of modified FOLFOX 6 followed by total mesorectal excision (TME) followed by an additional six cycles of FOLFOX 6.
The objectives of this study are the following:
- The primary endpoint of this trial is pathologic complete response (response rate).
- Secondary endpoints will include observation of overall pathologic response rate, correlation of pathologic staging with pre-operative ultrasound and pelvic MRI staging, as well as observation of toxic side effects, patterns of disease relapse, disease-free survival outcomes and overall survival outcomes.
Background Locally advanced rectal carcinoma continues to be a major oncologic problem in the United States. Several landmark studies have led to the current standard approach to the care of patients with stage II and III rectal cancer. In 1990 adjuvant 5- fluorouracil based chemoradiation became the accepted standard of care on the basis of two randomized trials. During the following two decades significant modifications were made to both the administration of chemoradiation therapy and surgery. First, continuous infusion 5-fluorouracil daily concurrent with radiation to was shown to be superior to bolus 5-fluorouracil for 3 consecutive days during weeks 1 and 5 of radiation. The overall rate of tumor relapse fell from 47% to 37%, and distant metastasis rate fell from 40% to 31%. Notably, local tumor recurrence was not significantly different between the two chemotherapy schedules. The improvement in relapse rate translated into a 4 year survival benefit, 70% versus 60%, favoring the protracted venous infusion of 5-fluorouracil (5-FU).
What is not known, however, is the relative contribution of radiation therapy to survival outcomes in the setting of chemotherapy programs for rectal cancer. Optimization of systemic therapy appears to have the most significant impact on survival outcomes. Firstly, patients may begin full systemic therapy with the regimen that has currently been identified as the most effective adjuvant treatment of stage III colon cancer. This relatively prompt initiation of 'full systemic dose' chemotherapy is in stark contrast to the typical paradigm of a 3-4 week interval between initial consultation and initiation of chemoradiation. Another theoretical advantage of this proposed trial lies in the fact that full systemic therapy is relatively uninterrupted. Therefore, the anticipated 6-8 week perioperative treatment free interval anticipated in this schema compares favorably with the typical 10-12 week perioperative treatment free interval with current standard of care neoadjuvant chemoradiation. Another important consideration favoring this chemotherapy is substantially less travel time/treatment time for patients and favorable toxicity profile given the elimination of daily neoadjuvant radiation.
Treatment Plan
Patients will be given:
- Modified FOLFOX6 will be given neoadjuvantly prior to resection for 3 months (6 cycles)
- Modified FOLFOX6 will be given adjuvantly within 6 weeks following resection for 3 months (6 cycles)
- Conditions
- Rectal Neoplasms
- Being tested
- FOLFOX, total mesorectal excision (TME)
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FOLFOXDrug
Also called oxaliplatin, leucovorin, 5-fluorouracil
6 cycles of neo-adjuvant mFOLFOX6
total mesorectal excision (TME)Procedure or surgery
Also called Total Mesorectal Excision
TME will be done 4-6 weeks after 6 cycles of neo-adjuvant FOLFOX.
| Study group | Role | What they receive |
|---|---|---|
| 6 cycles of FOLFOX pre and post TME | Experimental | Not described Receives: Drug: FOLFOX; Procedure: total mesorectal excision (TME) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response
Measured: 3-6 months
Secondary outcomes (1)
Observation of Overall Pathologic Response Rate, Correlation of Pathologic Staging With Pre-op Ultrasound and Pelvic MRI Staging Observed Toxicities Patterns of Disease Relapse Disease-free Survival Overall Survival
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2009 (estimated)
- Study startJan 2009
- Primary completionAug 2011
- Study completionAug 2011
Why it stopped: terminated for lack of enrollment
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 Rectal NeoplasmsStudies 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
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- St. Luke's-Roosevelt Hospital Center
- Responsible party
- Sponsor
- Investigators
- Peter Kozuch, MD, Principal investigator, Beth Israel Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00832299
- Sponsor's protocol ID
- 156-08
- Other IDs
- OX-08-006
- Status last verified
- Feb 2018
- First submitted
- 27 Jan 2009
- Last updated
- 1 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 1 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 Pre- Operative Chemotherapy With Six Cycles of Modified FOLFOX 6 Followed by Total Mesorectal Excision (TME) Followed by an Additional Six Cycles of FOLFOX 6
- ClinicalTrials.gov ID
- NCT00832299
- Acronym / sponsor ID
- 156-08
- Conditions
- Rectal Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: terminated for lack of enrollment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Beth Israel Medical CenterUniversity, hospital or other
- Collaborators
- St. Luke's-Roosevelt Hospital Center
- Study start
- Jan 2009
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 30 Jan 2009 (estimated)
- Results
- Posted 22 Apr 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase II open- labeled, prospective study to determine the efficacy of pre-operative chemotherapy with six cycles of modified FOLFOX 6 followed by total mesorectal excision (TME) followed by an additional six cycles of FOLFOX 6.
The objectives of this study are the following:
- The primary endpoint of this trial is pathologic complete response (response rate).
- Secondary endpoints will include observation of overall pathologic response rate, correlation of pathologic staging with pre-operative ultrasound and pelvic MRI staging, as well as observation of toxic side effects, patterns of disease relapse, disease-free survival outcomes and overall survival outcomes.
Detailed description
Principal Investigator: Peter Kozuch, M.D.
Sites: BIMC/SLRHC
Introduction
A Phase II open- labeled, prospective study to determine the efficacy of pre-operative chemotherapy with six cycles of modified FOLFOX 6 followed by total mesorectal excision (TME) followed by an additional six cycles of FOLFOX 6.
The objectives of this study are the following:
- The primary endpoint of this trial is pathologic complete response (response rate).
- Secondary endpoints will include observation of overall pathologic response rate, correlation of pathologic staging with pre-operative ultrasound and pelvic MRI staging, as well as observation of toxic side effects, patterns of disease relapse, disease-free survival outcomes and overall survival outcomes.
Background Locally advanced rectal carcinoma continues to be a major oncologic problem in the United States. Several landmark studies have led to the current standard approach to the care of patients with stage II and III rectal cancer. In 1990 adjuvant 5- fluorouracil based chemoradiation became the accepted standard of care on the basis of two randomized trials. During the following two decades significant modifications were made to both the administration of chemoradiation therapy and surgery. First, continuous infusion 5-fluorouracil daily concurrent with radiation to was shown to be superior to bolus 5-fluorouracil for 3 consecutive days during weeks 1 and 5 of radiation. The overall rate of tumor relapse fell from 47% to 37%, and distant metastasis rate fell from 40% to 31%. Notably, local tumor recurrence was not significantly different between the two chemotherapy schedules. The improvement in relapse rate translated into a 4 year survival benefit, 70% versus 60%, favoring the protracted venous infusion of 5-fluorouracil (5-FU).
What is not known, however, is the relative contribution of radiation therapy to survival outcomes in the setting of chemotherapy programs for rectal cancer. Optimization of systemic therapy appears to have the most significant impact on survival outcomes. Firstly, patients may begin full systemic therapy with the regimen that has currently been identified as the most effective adjuvant treatment of stage III colon cancer. This relatively prompt initiation of 'full systemic dose' chemotherapy is in stark contrast to the typical paradigm of a 3-4 week interval between initial consultation and initiation of chemoradiation. Another theoretical advantage of this proposed trial lies in the fact that full systemic therapy is relatively uninterrupted. Therefore, the anticipated 6-8 week perioperative treatment free interval anticipated in this schema compares favorably with the typical 10-12 week perioperative treatment free interval with current standard of care neoadjuvant chemoradiation. Another important consideration favoring this chemotherapy is substantially less travel time/treatment time for patients and favorable toxicity profile given the elimination of daily neoadjuvant radiation.
Treatment Plan
Patients will be given:
- Modified FOLFOX6 will be given neoadjuvantly prior to resection for 3 months (6 cycles)
- Modified FOLFOX6 will be given adjuvantly within 6 weeks following resection for 3 months (6 cycles)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 6 cycles of FOLFOX pre and post TME | Experimental | Drug: FOLFOX, Procedure: total mesorectal excision (TME) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must consent to participate in the study and must have signed and dated an IRB-approved consent form conforming to federal and institutional guidelines
- Patient must have histologically proven adenocarcinoma of the rectum with no distant metastases
- Tumor stage must be T3N0M0, T1-3 N1M0 assessed by clinical exam, TRUS, MRI and CT. Pre-operative evidence of T4, N2 or distal lesions (0-6 cm from anal verge) should receive preoperative RT and not be offered this protocol. Any pT4, pN2 or CRM+ patients should be offered postoperative radiation
- The proximal border of the tumor must be at or below 12 centimeters of the anal verge by proctoscopic examination
- The distal border of the tumor must be at or above 6 cm from the anal verge on preoperative proctoscopy with the patient in the left lateral decubitus position
Key exclusion criteria (10 listed)
- Patients can not be receiving any other investigational agents
- Patients with known metastases will be excluded from the study
- Patients with history of significant neuropathy or current symptoms of neuropathy
- Patients with history of allergic reactions attributed to compounds of similar chemical or biologic composition to oxaliplatin or 5-FU or leucovorin
- Patients with uncontrolled intercurrent illness not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
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 |
|---|---|---|
| FOLFOXAlso: oxaliplatin, leucovorin, 5-fluorouracil6 cycles of neo-adjuvant mFOLFOX6 | Drug | 6 cycles of FOLFOX pre and post TME |
| total mesorectal excision (TME)Also: Total Mesorectal ExcisionTME will be done 4-6 weeks after 6 cycles of neo-adjuvant FOLFOX. | Procedure or surgery | 6 cycles of FOLFOX pre and post TME |
Primary outcome
Pathologic Complete Response
Time frame: 3-6 months
1 secondary outcome
Observation of Overall Pathologic Response Rate, Correlation of Pathologic Staging With Pre-op Ultrasound and Pelvic MRI Staging Observed Toxicities Patterns of Disease Relapse Disease-free Survival Overall Survival
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 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 FOLFOX and total mesorectal excision (TME) in people with Rectal Neoplasms, 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 10 inclusion and 10 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: stopped early, as of the sponsor's last update on 1 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 22 Apr 2013). 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 Complete Response (time frame: 3-6 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 1 Mar 2018.