Rectal CancerPhase 1/2NCT00307736
Bevacizumab, Erlotinib and 5-Fluorouracil With External Beam Radiation Therapy in Locally Advanced Rectal Cancer
A Phase 1/2 study testing 5-fluorouracil, bevacizumab and erlotinib in people with Rectal Cancer and Adenocarcinoma of the Rectum, run by Massachusetts General Hospital at 3 sites in United States.
Trial summary
The purpose of this study is determine the safety of 5-fluorouracil, bevacizumab and erlotinib when administered in combination with external beam radiation therapy(Phase I portion) as well as to begin to collect information about whether this combination treatment is effective in treating(Phase II portion) patients… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer, Adenocarcinoma of the Rectum
- What is being tested?
- 5-fluorouracil, bevacizumab and erlotinib
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 3 sitesUnited States
- Study dates
- May 2006to Jul 2011
- Phase
- Phase 1/2
- 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 primary adenocarcinoma of the rectum that begins within 15cm of the anal verge as determined by sigmoidoscopy or colonoscopy
- Clinical T3 or T4 tumors as determined by endoscopic ultrasound and/or rectal MRI
- ECOG performance status of 0-2
- 18 years of age or older
- Creatinine of < 2.0
- Adequate hepatic function
- Adequate hematopoietic function
- Use of effective means of contraception in subjects of child-bearing potential
Who cannot join
- Evidence of metastatic disease as determined by chest/abdominal/pelvic CT or physical exam
- Prior chemotherapy or radiation therapy for treatment of colorectal cancer
- Prior treatment with 5-FU
- Prior treatment with a tyrosine kinase inhibitor, EGFR inhibitor, or VEGF inhibitor
- Patients must not be receiving any other investigational agent
- Prior malignancy within the last 5 years except for completely excised skin cancer, in situ cervical cancer
Show all 24Show fewer
- Warfarin anticoagulation
- Co-existent malignant disease
- Current or recent participation in a clinical trial (within 4 weeks from the first day of treatment)
- Pregnancy
- Blood pressure of >150/100 mmHg
- Unstable angina
- NYHA Grade II or greater congestive heart failure
- History of myocardial infarction within 6 months
- History of stroke within 6 months
- Clinically significant peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Presence of central nervous system or brain metastases
- Major surgical procedure, open biopsy, or significant trauma injury within 28 days prior to day 0, anticipation of need for major surgical procedure during the course of the study
- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 0
- Pregnant or lactating
- Urine protein:creatinine ratio > or equal to one at screening
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0]
- Serious, non-healing wound, ulcer, or bone fracture
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Massachusetts General Hospital
Boston, Massachusetts, 02115
About this study
Official title: A Phase I/II Study of Bevacizumab, Erlotinib and 5-fluorouracil With Concurrent External Beam Radiation Therapy in Locally Advanced Rectal Cancer
The purpose of this study is determine the safety of 5-fluorouracil, bevacizumab and erlotinib when administered in combination with external beam radiation therapy(Phase I portion) as well as to begin to collect information about whether this combination treatment is effective in treating(Phase II portion) patients with locally advanced rectal cancer.
Read the detailed description
- All participants will receive the following drugs: 5-fluorouracil (5-FU) given as a continuous 24-hour infusion; Bevacizumab given intravenously; erlotinib given orally at home. In the Phase I portion, we are looking for the highest dose of erlotinib that can be given safely in combination with the 5-FU, bevacizumab and radiation therapy. Therefore the dose of erlotinib may not be the same for each participant. The dose will increase until we find the highest dose without causing serious or unmanageable side effects.
- Study treatment is given as an outpatient and consists of 14 day cycles with a total of 3 cycles. Patients will be given all three study drugs and radiation therapy on a monday (unless a monday falls on on a holiday). This will be day 1 of the first treatment cycle. 5-FU is given continuously days 1-14. Bevacizumab is given on day 1. Erlotinib will be given on days 1-14. Radiation therapy will be performed on Days 1-5 and 8-12.
- The following tests and procedures will be performed weekly while participants are receiving study treatment: physical examination, measurement of vital signs, height and weight; performance status; blood work, urine sample.
- At the end of treatment the following tests will be performed: physical examination and measurement of vital signs; performance status; blood work; CT scans of chest, abdomen and pelvis. Patients will also be evaluated for surgery at this time. Patients will be followed every three months for the first three years after surgery, then every 6 months for the next two years.
- Conditions
- Rectal Cancer, Adenocarcinoma of the Rectum
- Being tested
- 5-fluorouracil, bevacizumab, erlotinib, External beam radiation therapy (EBRT)
- Keywords
- Fluorouracil, bevacizumab, erlotinib, external beam radiation therapy, EBRT
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-fluorouracilDrug
Given as a 24-hour infusion on days 1-14 of each 14-day cycle for a total of 3 cycles.
bevacizumabDrug
Given intravenously on day 1 of each 14-day cycle for a total of 3 cycles.
erlotinibDrug
Taken orally on days 1-14 of each 14-day cycle for a total of 3 cycles.
External beam radiation therapy (EBRT)Procedure or surgery
Given on days 1-5 and 8-12
| Study group | Role | What they receive |
|---|---|---|
| Chemotherapy and radiation | Experimental | Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation. Receives: Drug: 5-fluorouracil; Drug: bevacizumab; Drug: erlotinib; Procedure: External beam radiation therapy (EBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Erlotinib When Administered in Combination With 5-fluorouracil (5-FU), Bevacizumab, and External Beam Radiation Therapy
MTD of Erlotinib was determined using a traditional 3 + 3 dose escalation scheme of three dose levels (50,100,150mg). Successive cohorts of 3-6 patients were enrolled into dose escalation cohorts for 14 day cycles. MTD reflects the highest dose of Erlotinib that had ≤1 out of 6 patients with Dose-Limiting Toxicity (DLT) at the highest dose level below the maximally administered dose. The maximally administered dose is the first dose that causes DLT in >33% of patients. DLT was defined as: Any grade 4 neutropenia, Any grade 3 thrombocytopenia, or Any ≥ grade 3 non-hematologic toxicity that results in greater than 7 days interruption in therapy.
Measured: 3 years
Secondary outcomes (3)
Summary of Grade 3 or Greater Toxicity
Summary of grade 3 or greater toxicity by grade and type. All adverse events were evaluated using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Grade 3: Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living.
Grade 4 Life-threatening consequences; urgent intervention indicated.
Measured: 3 years
Percentage of Participants With Disease-free Survival
Summary of disease free survival at 1, 2, and 3 years. Disease free survival is the length of time after primary treatment for cancer ends that the participant survives without any clinical signs or symptoms of that cancer. The data is shown of the percentage of participants still in disease free survival at one, two, and three years.
Measured: 1, 2, 3 years
Post-operative Complications After Resection of Rectal Cancers Following Preoperative 5-FU, Bevacizumab, Erlotinib, and External Beam Radiation Therapy.
Surgical morbidity following R0 resection with one of the following procedures: abdominal perineal resection, low anterior resection, and low anterior resection with coloanal anastomosis.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2006 (estimated)
- Study startMay 2006
- Primary completionApr 2010
- Study completionJul 2011
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lawrence S. Blaszkowsky, MD, Massachusetts General Hospital
- Investigators
- Lawrence S. Blaszkowsky, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00307736
- Sponsor's protocol ID
- 05-345
- Status last verified
- Mar 2017
- First submitted
- 24 Mar 2006
- Last updated
- 10 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Blaszkowsky LS, Ryan DP, Szymonifka J, Borger DR, Zhu AX, Clark JW, Kwak EL, Mamon HJ, Allen JN, Vasudev E, Shellito PC, Cusack JC, Berger DL, Hong TS. Phase I/II study of neoadjuvant bevacizumab, erlotinib and 5-fluorouracil with concurrent external beam radiation therapy in locally advanced rectal cancer. Ann Oncol. 2014 Jan;25(1):121-6. doi: 10.1093/annonc/mdt516.
PubMed 24356623
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Bevacizumab, Erlotinib and 5-fluorouracil With Concurrent External Beam Radiation Therapy in Locally Advanced Rectal Cancer
- ClinicalTrials.gov ID
- NCT00307736
- Acronym / sponsor ID
- 05-345
- Conditions
- Rectal Cancer, Adenocarcinoma of the Rectum
- Keywords
- Fluorouracil, bevacizumab, erlotinib, external beam radiation therapy, EBRT
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute, Genentech, Inc.
- Study start
- May 2006
- Primary completion
- Apr 2010 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 28 Mar 2006 (estimated)
- Results
- Posted 10 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is determine the safety of 5-fluorouracil, bevacizumab and erlotinib when administered in combination with external beam radiation therapy(Phase I portion) as well as to begin to collect information about whether this combination treatment is effective in treating(Phase II portion) patients with locally advanced rectal cancer.
Detailed description
- All participants will receive the following drugs: 5-fluorouracil (5-FU) given as a continuous 24-hour infusion; Bevacizumab given intravenously; erlotinib given orally at home. In the Phase I portion, we are looking for the highest dose of erlotinib that can be given safely in combination with the 5-FU, bevacizumab and radiation therapy. Therefore the dose of erlotinib may not be the same for each participant. The dose will increase until we find the highest dose without causing serious or unmanageable side effects.
- Study treatment is given as an outpatient and consists of 14 day cycles with a total of 3 cycles. Patients will be given all three study drugs and radiation therapy on a monday (unless a monday falls on on a holiday). This will be day 1 of the first treatment cycle. 5-FU is given continuously days 1-14. Bevacizumab is given on day 1. Erlotinib will be given on days 1-14. Radiation therapy will be performed on Days 1-5 and 8-12.
- The following tests and procedures will be performed weekly while participants are receiving study treatment: physical examination, measurement of vital signs, height and weight; performance status; blood work, urine sample.
- At the end of treatment the following tests will be performed: physical examination and measurement of vital signs; performance status; blood work; CT scans of chest, abdomen and pelvis. Patients will also be evaluated for surgery at this time. Patients will be followed every three months for the first three years after surgery, then every 6 months for the next two years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chemotherapy and radiation | Experimental | Drug: 5-fluorouracil, Drug: bevacizumab, Drug: erlotinib, Procedure: External beam radiation therapy (EBRT)Continuous infusion 5-fluorouracil 225 mg/M2/d, bevacizumab 5 mg/kg IV q 14 days, erlotinib 50-150 mg orally daily for duration of radiation. |
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 confirmed primary adenocarcinoma of the rectum that begins within 15cm of the anal verge as determined by sigmoidoscopy or colonoscopy
- Clinical T3 or T4 tumors as determined by endoscopic ultrasound and/or rectal MRI
- ECOG performance status of 0-2
- 18 years of age or older
- Creatinine of < 2.0
Key exclusion criteria (24 listed)
- Evidence of metastatic disease as determined by chest/abdominal/pelvic CT or physical exam
- Prior chemotherapy or radiation therapy for treatment of colorectal cancer
- Prior treatment with 5-FU
- Prior treatment with a tyrosine kinase inhibitor, EGFR inhibitor, or VEGF inhibitor
- Patients must not be receiving any other investigational agent
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-fluorouracilGiven as a 24-hour infusion on days 1-14 of each 14-day cycle for a total of 3 cycles. | Drug | Chemotherapy and radiation |
| bevacizumabGiven intravenously on day 1 of each 14-day cycle for a total of 3 cycles. | Drug | Chemotherapy and radiation |
| erlotinibTaken orally on days 1-14 of each 14-day cycle for a total of 3 cycles. | Drug | Chemotherapy and radiation |
| External beam radiation therapy (EBRT)Given on days 1-5 and 8-12 | Procedure or surgery | Chemotherapy and radiation |
Primary outcome
Maximum Tolerated Dose (MTD) of Erlotinib When Administered in Combination With 5-fluorouracil (5-FU), Bevacizumab, and External Beam Radiation Therapy
Time frame: 3 years
MTD of Erlotinib was determined using a traditional 3 + 3 dose escalation scheme of three dose levels (50,100,150mg). Successive cohorts of 3-6 patients were enrolled into dose escalation cohorts for 14 day cycles. MTD reflects the highest dose of Erlotinib that had ≤1 out of 6 patients with Dose-Limiting Toxicity (DLT) at the highest dose level below the maximally administered dose. The maximally administered dose is the first dose that causes DLT in >33% of patients. DLT was defined as: Any grade 4 neutropenia, Any grade 3 thrombocytopenia, or Any ≥ grade 3 non-hematologic toxicity that results in greater than 7 days interruption in therapy.
3 secondary outcomes
Summary of Grade 3 or Greater Toxicity
Time frame: 3 years
Percentage of Participants With Disease-free Survival
Time frame: 1, 2, 3 years
Post-operative Complications After Resection of Rectal Cancers Following Preoperative 5-FU, Bevacizumab, Erlotinib, and External Beam Radiation Therapy.
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24356623Blaszkowsky LS, Ryan DP, Szymonifka J, Borger DR, Zhu AX, Clark JW, Kwak EL, Mamon HJ, Allen JN, Vasudev E, Shellito PC, Cusack JC, Berger DL, Hong TS. Phase I/II study of neoadjuvant bevacizumab, erlotinib and 5-fluorouracil with concurrent external beam radiation therapy in locally advanced rectal cancer. Ann Oncol. 2014 Jan;25(1):121-6. doi: 10.1093/annonc/mdt516.
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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.
Lawrence S. Blaszkowsky, MD principal investigator
Massachusetts General Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 5-fluorouracil, bevacizumab and erlotinib in people with Rectal Cancer and Adenocarcinoma of the Rectum, run by Massachusetts General Hospital at 3 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 24 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 10 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 10 May 2017). 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?
Maximum Tolerated Dose (MTD) of Erlotinib When Administered in Combination With 5-fluorouracil (5-FU), Bevacizumab, and External Beam Radiation Therapy (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00307736, which also lists 1 linked publication.
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 10 May 2017.