Rectal CancerPhase 2NCT00611858
Cetuximab, 5-FU and Radiation as Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer
A Phase 2 study testing Cetuximab, 5-Fluorouracil and Radiation in people with Rectal Cancer, run by Dana-Farber Cancer Institute at 4 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Cetuximab, 5-Fluorouracil and Radiation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 4 sitesUnited States
- Study dates
- May 2008to Sep 2016
- 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 confirmed adenocarcinoma of the rectum that begins within 15cm of the anal verge as determined by sigmoidoscopy and/or colonoscopy, with no evidence of distant metastatic disease. A complete colonoscopy to the cecum is recommended prior to initiating protocol therapy.
- Staging with transrectal ultrasound or endorectal coil Magnetic resonance imaging (MRI) to confirm clinical stage of T3 or T4 or lymph node positive rectal adenocarcinoma
- Tumor is K-ras wildtype by method of choice at respective institution (testing codons 12 and 13)
- Performance status: Eastern Cooperative Oncology Group Performance Score (ECOG PS) less than or equal to 2
- 18 years of age or older
- No evidence of metastatic disease by abdominal/pelvic (Computed tomography) CT and chest imaging
Show all 9Show fewer
- Adequate bone marrow, renal,and hepatic function as outlined in protocol
- All patients will be evaluated by a surgeon and considered a candidate for definitive surgery
- Coumadin or heparin management for line care of other indications is permitted. The International Normalised Ratio (INR) will be monitored weekly in patients taking coumadin.
Who cannot join
- Prior treatment for this malignancy
- Prior history of pelvic radiation therapy
- Prior history of 5-FU based or EGFR receptor inhibitor therapy
- Prior history of an allergic reaction to a monoclonal antibody
- Uncontrolled serious medical or psychiatric illness
- Significant history of uncontrolled cardiac disease
- Sexually active women of childbearing potential must use an effective method of birth control during the course of the study
- Unwilling to agree to pre and post-cetuximab sigmoidoscopy and biopsy
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Vanderbilt Medical Center
Nashville, Tennessee
South Shore Hospital
Weymouth, Massachusetts
About this study
Official title: Phase II Study of Cetuximab, 5-FU and Radiation as Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer
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.
Read the detailed description
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.
- Conditions
- Rectal Cancer
- Being tested
- Cetuximab, 5-Fluorouracil, Radiation
- Keywords
- 5-FU, cetuximab, radiation, adenocarcinoma of the rectum, neoadjuvant therapy
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
Also called Erbitux
5-FluorouracilDrug
Also called 5-FU
RadiationRadiation
Also called External Beam Radiation Therapy
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Cetuximab; Drug: 5-Fluorouracil; Radiation: Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Disease is assessed at the time of surgery which in this study cohort occurred up to 24 weeks from date of registration.
Secondary outcomes (5)
Local Recurrence Rate
Local recurrence rate is the percentage of participants experiencing recurrence within the pelvis.
Measured: 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.
Complete Resection Rate
Complete resection rate is the percentage of participants having all gross disease removed by the surgeon at the time of operation.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2008 (estimated)
- Study startMay 2008
- Primary completionDec 2012
- Study completionSep 2016
Why it stopped: Slow accrual
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 CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- 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
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Bristol-Myers Squibb
- Responsible party
- Principal investigator, Jeffrey A. Meyerhardt, MD, Dana-Farber Cancer Institute
- Investigators
- Jeffrey Meyerhardt, MD, MPH, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00611858
- Sponsor's protocol ID
- 07-297
- Other IDs
- BMS CA225302
- Status last verified
- Dec 2018
- First submitted
- 29 Jan 2008
- Last updated
- 8 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Cetuximab, 5-FU and Radiation as Neoadjuvant Therapy for Patients With Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT00611858
- Acronym / sponsor ID
- 07-297
- Conditions
- Rectal Cancer
- Keywords
- 5-FU, cetuximab, radiation, adenocarcinoma of the rectum, neoadjuvant therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Massachusetts General Hospital, Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Bristol-Myers Squibb
- Study start
- May 2008
- Primary completion
- Dec 2012 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 11 Feb 2008 (estimated)
- Results
- Posted 14 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cetuximab, 5-FU and Radiation | Experimental | Drug: Cetuximab, Drug: 5-Fluorouracil, Radiation: RadiationCetuximab: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically confirmed adenocarcinoma of the rectum that begins within 15cm of the anal verge as determined by sigmoidoscopy and/or colonoscopy, with no evidence of distant metastatic disease. A complete colonoscopy to the cecum is recommended prior to initiating protocol therapy.
- Staging with transrectal ultrasound or endorectal coil Magnetic resonance imaging (MRI) to confirm clinical stage of T3 or T4 or lymph node positive rectal adenocarcinoma
- Tumor is K-ras wildtype by method of choice at respective institution (testing codons 12 and 13)
- Performance status: Eastern Cooperative Oncology Group Performance Score (ECOG PS) less than or equal to 2
- 18 years of age or older
Key exclusion criteria (8 listed)
- Prior treatment for this malignancy
- Prior history of pelvic radiation therapy
- Prior history of 5-FU based or EGFR receptor inhibitor therapy
- Prior history of an allergic reaction to a monoclonal antibody
- Uncontrolled serious medical or psychiatric illness
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 |
|---|---|---|
| CetuximabAlso: Erbitux | Drug | Cetuximab, 5-FU and Radiation |
| 5-FluorouracilAlso: 5-FU | Drug | Cetuximab, 5-FU and Radiation |
| RadiationAlso: External Beam Radiation Therapy | Radiation | Cetuximab, 5-FU and Radiation |
Primary outcome
Pathological Complete Response Rate
Time frame: Disease is assessed at the time of surgery which in this study cohort occurred up to 24 weeks from date of registration.
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).
5 secondary outcomes
Local Recurrence Rate
Time frame: 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.
Complete Resection Rate
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Mean follow-up for this study cohort was 4.4 years from study entry, up to 7.9 years.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Jeffrey Meyerhardt, MD, MPH principal investigator
Dana-Farber Cancer Institute
4 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 Cetuximab, 5-Fluorouracil and Radiation in people with Rectal Cancer, run by Dana-Farber Cancer Institute at 4 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 9 inclusion and 8 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 8 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 14 Nov 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?
Pathological Complete Response Rate (time frame: Disease is assessed at the time of surgery which in this study cohort occurred up to 24 weeks from date of registration.). 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 8 Jan 2019.