Rectal CancerPhase 1NCT01376453
Pre-operative 5-Fluorouracil (5-FU) and Sorafenib With External Radiation in Locally Advanced Rectal Cancer
A Phase 1 study testing Sorafenib, 5-Fluorouracil (5-FU) and Radiation in people with Rectal Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The main purpose of this study is to find the maximum tolerable dose of sorafenib when administered along with another drug called 5-Fluorouracil (5-FU) and to find out more about whether these drugs, along with radiation, can help people with rectal cancer when given before surgery. 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?
- Sorafenib, 5-Fluorouracil (5-FU) and Radiation
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2011to Mar 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 12 cm of the anal verge as determined by sigmoidoscopy and/or colonoscopy with no evidence of distant metastasis
- Locally advanced rectal cancer determined by any of the following features: Fixed or immobile tumor on physical exam and/or; T3 disease with invasion through the muscularis propria as defined by transrectal ultrasound, CT or MRI; T4 disease with invasion of adjacent structures such as pelvic sidewall, sacrum, pelvis, bladder and/or prostate as determined appropriate imaging modalities such as ultrasound, CT or MRI; Any T with + N on CT scan/MRI or transrectal ultrasound
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- Adequate bone marrow, liver and renal function as assessed by the following: Hemoglobin > 9.0 g/dl, Absolute neutrophil count (ANC) > 1,500/mm^3, Platelet count > 100,000/mm^3, Total bilirubin < 1.5 times upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 times the ULN ( < 5 x ULN for patients with liver involvement), Creatinine < 1.5 times ULN
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
- Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of sorafenib.
- Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
- Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin will be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until international normalized ratio (INR) is stable.
Who cannot join
- Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
- Pelvic irradiation therapy.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
- Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
- Active clinically serious infection > Common Terminology Criteria for Adverse Events (CTCAE) Grade 2.
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- Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic, attacks, deep vein thrombosis (DVT) within the past 6 months.
- No active malignancy except for nonmelanoma skin cancer or in situ cervical cancer or Treated non-pelvic cancer from which the patient has been continuously disease free more than five years.
- Needing medical attention for serious bleeding in past 4 weeks.
- Previous chemotherapy except for antiangiogenic agent or tyrosine kinase inhibitor (TKI) will be allowed as long as it is more than 5 years.
- Evidence or history of bleeding diathesis
- Use of St. John's Wort or rifampin
- Known or suspected allergy to sorafenib or any agent given in the course of this trial.
- Any condition that impairs patient's ability to swallow whole pills.
- Any malabsorption problem.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: Phase I Study of Pre-operative Continuous 5-FU, and Sorafenib With External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma
The main purpose of this study is to find the maximum tolerable dose of sorafenib when administered along with another drug called 5-Fluorouracil (5-FU) and to find out more about whether these drugs, along with radiation, can help people with rectal cancer when given before surgery. 5-FU and radiation are both approved by the US Food and Drug Administration (FDA) for use in people with rectal cancer.
The investigators will utilize a standard 3 + 3 phase I study design. In the phase I part of the study, the investigators will attempt dose escalation of sorafenib in combination with standard infusional 5-FU and external beam at standard doses. Clinical staging should be done by endorectal ultrasound (ERUS) and/or pelvic magnetic resonance imaging (MRI) for T and N stage; chest and abdomen computed tomography (CT) for staging of metastatic disease; undergo sigmoidoscopy and/or colonoscopy done by crude odds ratios (CORS); biopsy is taken for diagnosis and extra is sent for tissue bank. At the maximum tolerated dose (MTD) of sorafenib we will expand the cohort to 6 more patients to further evaluate toxicity profile and efficacy.
Read the detailed description
Participants' study regimen will include 5 ½ weeks of radiation. Radiation sessions will be daily, Monday through Friday, except for holidays. 5-FU will be delivered at a dose of 225 mg/m² daily through a catheter in a large vein continuously until the last day of radiation. In addition, sorafenib will be taken by mouth twice daily every day until the last day of radiation. The dose of sorafenib participants may receive will be one of the following: 200 mg every other day, 200 mg daily, 400 mg daily, or 800 mg daily. Following completion of this phase of the study, participants will receive no study drug or radiation for one month. At 4 to 5 weeks after stopping study drug and radiation, participants will have another CT scan or MRI to assess their cancer. About 6 to 8 weeks after the end of radiation, participants will undergo surgery and every effort will be made to remove the tumor. The surgery will occur just as it would if participants were not in the study, except that a portion of their tumor obtained during surgery will be used for research biomarker testing (as described in the consent form).
Approximately 6 -10 weeks after participants' surgery, when they have adequately healed, they may receive additional chemotherapy at their study doctor's discretion.
- Conditions
- Rectal Cancer
- Keywords
- External Radiation Therapy, Locally Advanced Rectal, Adenocarcinoma
- Medical subject headings
- Rectal Neoplasms, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SorafenibDrug
Also called BAY 43-9006, NSC 724772, Nexavar®
In addition to radiation and 5-FU, sorafenib will be taken by mouth daily every day until the last day of radiation. The dose of sorafenib will be one of the following: 200 mg every other day, 200 mg daily, 400 mg daily, or 800 mg daily
5-Fluorouracil (5-FU)Drug
Also called Adrucil®, Carac™, Efudex®, Fluoroplex®
5-FU will be delivered at a dose of 225 mg/m^2 daily through a catheter in a large vein continuously until the last day of radiation.
RadiationRadiation
Radiation sessions will be daily, Monday through Friday, except for holidays.
| Study group | Role | What they receive |
|---|---|---|
| Sorafenib Dose Escalation | Experimental | Pre-operative Continuous 5-FU, and Sorafenib with External Radiation Therapy. Dose level -1 will only be evaluated if dose level 1 exceeds MTD. The sorafenib and infusional 5-FU will only be given Day 1-5(Monday-Friday) with radiation only. Receives: Drug: Sorafenib; Drug: 5-Fluorouracil (5-FU); Radiation: Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
To determine maximally tolerated dose of sorafenib when delivered concurrently with 5-FU and external beam radiation in patients with locally advanced rectal adenocarcinoma
Measured: Start of treatment through end of follow up - average of 21 weeks
Secondary outcomes (2)
Number of Participants With Pathologic Response
To determine the pathologic response rate after pre-operative therapy and surgery
Measured: Start of treatment through end of follow up - average of 21 weeks
Number of Participants With Serious Adverse Events (SAEs)
To further define safety profile of the combination. During the 5 1/2 weeks of radiation, participants will be seen in the study clinic and will have blood tests weekly.
Measured: Start of treatment through end of follow up - average of 21 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2011 (estimated)
- Study startJun 2011
- Primary completionNov 2014
- Study completionMar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 H. Lee Moffitt Cancer Center and Research 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Richard Kim, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01376453
- Sponsor's protocol ID
- MCC-16475
- Other IDs
- IST 000575
- Status last verified
- Apr 2016
- First submitted
- 16 Jun 2011
- Last updated
- 12 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kim R, Prithviraj GK, Shridhar R, Hoffe SE, Jiang K, Zhao X, Chen DT, Almhanna K, Strosberg J, Campos T, Shibata D. Phase I study of pre-operative continuous 5-FU and sorafenib with external radiation therapy in locally advanced rectal adenocarcinoma. Radiother Oncol. 2016 Feb;118(2):382-6. doi: 10.1016/j.radonc.2016.01.018. Epub 2016 Feb 6.
PubMed 26861740
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Pre-operative Continuous 5-FU, and Sorafenib With External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma
- ClinicalTrials.gov ID
- NCT01376453
- Acronym / sponsor ID
- MCC-16475
- Conditions
- Rectal Cancer
- Keywords
- External Radiation Therapy, Locally Advanced Rectal, Adenocarcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Jun 2011
- Primary completion
- Nov 2014 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 20 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to find the maximum tolerable dose of sorafenib when administered along with another drug called 5-Fluorouracil (5-FU) and to find out more about whether these drugs, along with radiation, can help people with rectal cancer when given before surgery. 5-FU and radiation are both approved by the US Food and Drug Administration (FDA) for use in people with rectal cancer.
The investigators will utilize a standard 3 + 3 phase I study design. In the phase I part of the study, the investigators will attempt dose escalation of sorafenib in combination with standard infusional 5-FU and external beam at standard doses. Clinical staging should be done by endorectal ultrasound (ERUS) and/or pelvic magnetic resonance imaging (MRI) for T and N stage; chest and abdomen computed tomography (CT) for staging of metastatic disease; undergo sigmoidoscopy and/or colonoscopy done by crude odds ratios (CORS); biopsy is taken for diagnosis and extra is sent for tissue bank. At the maximum tolerated dose (MTD) of sorafenib we will expand the cohort to 6 more patients to further evaluate toxicity profile and efficacy.
Detailed description
Participants' study regimen will include 5 ½ weeks of radiation. Radiation sessions will be daily, Monday through Friday, except for holidays. 5-FU will be delivered at a dose of 225 mg/m² daily through a catheter in a large vein continuously until the last day of radiation. In addition, sorafenib will be taken by mouth twice daily every day until the last day of radiation. The dose of sorafenib participants may receive will be one of the following: 200 mg every other day, 200 mg daily, 400 mg daily, or 800 mg daily. Following completion of this phase of the study, participants will receive no study drug or radiation for one month. At 4 to 5 weeks after stopping study drug and radiation, participants will have another CT scan or MRI to assess their cancer. About 6 to 8 weeks after the end of radiation, participants will undergo surgery and every effort will be made to remove the tumor. The surgery will occur just as it would if participants were not in the study, except that a portion of their tumor obtained during surgery will be used for research biomarker testing (as described in the consent form).
Approximately 6 -10 weeks after participants' surgery, when they have adequately healed, they may receive additional chemotherapy at their study doctor's discretion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sorafenib Dose Escalation | Experimental | Drug: Sorafenib, Drug: 5-Fluorouracil (5-FU), Radiation: RadiationPre-operative Continuous 5-FU, and Sorafenib with External Radiation Therapy. Dose level -1 will only be evaluated if dose level 1 exceeds MTD. The sorafenib and infusional 5-FU will only be given Day 1-5(Monday-Friday) with radiation only. |
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 adenocarcinoma of the rectum that begins within 12 cm of the anal verge as determined by sigmoidoscopy and/or colonoscopy with no evidence of distant metastasis
- Locally advanced rectal cancer determined by any of the following features: Fixed or immobile tumor on physical exam and/or; T3 disease with invasion through the muscularis propria as defined by transrectal ultrasound, CT or MRI; T4 disease with invasion of adjacent structures such as pelvic sidewall, sacrum, pelvis, bladder and/or prostate as determined appropriate imaging modalities such as ultrasound, CT or MRI; Any T with + N on CT scan/MRI or transrectal ultrasound
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- Adequate bone marrow, liver and renal function as assessed by the following: Hemoglobin > 9.0 g/dl, Absolute neutrophil count (ANC) > 1,500/mm^3, Platelet count > 100,000/mm^3, Total bilirubin < 1.5 times upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 times the ULN ( < 5 x ULN for patients with liver involvement), Creatinine < 1.5 times ULN
- Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
Key exclusion criteria (15 listed)
- Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
- Pelvic irradiation therapy.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
- Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
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 |
|---|---|---|
| SorafenibAlso: BAY 43-9006, NSC 724772, Nexavar®In addition to radiation and 5-FU, sorafenib will be taken by mouth daily every day until the last day of radiation. The dose of sorafenib will be one of the following: 200 mg every other day, 200 mg daily, 400 mg daily, or 800 mg daily | Drug | Sorafenib Dose Escalation |
| 5-Fluorouracil (5-FU)Also: Adrucil®, Carac™, Efudex®, Fluoroplex®5-FU will be delivered at a dose of 225 mg/m^2 daily through a catheter in a large vein continuously until the last day of radiation. | Drug | Sorafenib Dose Escalation |
| RadiationRadiation sessions will be daily, Monday through Friday, except for holidays. | Radiation | Sorafenib Dose Escalation |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: Start of treatment through end of follow up - average of 21 weeks
To determine maximally tolerated dose of sorafenib when delivered concurrently with 5-FU and external beam radiation in patients with locally advanced rectal adenocarcinoma
2 secondary outcomes
Number of Participants With Pathologic Response
Time frame: Start of treatment through end of follow up - average of 21 weeks
Number of Participants With Serious Adverse Events (SAEs)
Time frame: Start of treatment through end of follow up - average of 21 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2016.
- Derived from this study: PubMed 26861740Kim R, Prithviraj GK, Shridhar R, Hoffe SE, Jiang K, Zhao X, Chen DT, Almhanna K, Strosberg J, Campos T, Shibata D. Phase I study of pre-operative continuous 5-FU and sorafenib with external radiation therapy in locally advanced rectal adenocarcinoma. Radiother Oncol. 2016 Feb;118(2):382-6. doi: 10.1016/j.radonc.2016.01.018. Epub 2016 Feb 6.
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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.
Richard Kim, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sorafenib, 5-Fluorouracil (5-FU) and Radiation in people with Rectal Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site 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 15 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 12 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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) (time frame: Start of treatment through end of follow up - average of 21 weeks). 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 NCT01376453, 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 12 Sep 2016.