Colorectal CancerPhase 2NCT01367275
Irinotecan Plus Brivanib in Metastatic Colorectal Cancer (CRC) Enriched for Elevated Levels of Plasma FGF
A Phase 2 study testing Brivanib and Irinotecan in people with Colorectal Cancer and Colorectal Adenocarcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to learn if adding brivanib to irinotecan can help control the disease in patients with colorectal cancer that has spread. The safety of this drug combination will also be studied. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Colorectal Adenocarcinoma
- What is being tested?
- Brivanib and Irinotecan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2011to Nov 2013
- 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
- Signed written Informed Consent.
- Patient must have progressed on front-line chemotherapy treatment containing bevacizumab for histologically confirmed colorectal adenocarcinoma that is unresectable or metastatic. Progression is defined as either radiographic or clinical progression.
- Patient must have measurable lesions as defined by RECIST version 1.1 criteria.
- ECOG performance status 0-2.
- Known bFGF level performed by a CLIA-certified laboratory performed during or within 12 weeks of last bevacizumab treatment
- Enrollment in the "Assessment of Targeted Therapies Against Colorectal Cancer" (ATTACC) protocol 2009-0091.
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- LVEF > 50% measured by 2-D echocardiogram
- Bone marrow function defined as the following: An absolute neutrophil count (ANC) =/>1,500/mcl; Platelets =/>100,000/mcl; Hemoglobin =/> 8.5 g/dl.
- Renal function defined as the following: Serum creatinine less than or equal to 1.5 x institutional upper limit normal (ULN).
- Hepatic function defined as the following: Serum total bilirubin < 1.5 x ULN; AST (SGOT), ALT (SGPT) and alkaline phosphatase =/< 2.5 x ULN; Serum albumin =/> 2.5 g/dl; If liver involvement, AST, ALT, and alkaline phosphatase =/< 5.0 x ULN.
- International normalized ratio (INR) =/< 2.3 or Prothrombin Time (PT) =/< 6 seconds above control unless patient is currently receiving warfarin therapy for the treatment or prevention of venous thrombosis.
- Men and women, age =/> 18 years.
- A male subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study [and for up to 12 weeks after the last dose of study drug] to minimize the risk of pregnancy. If the partner is pregnant or breastfeeding, the subject must use a condom.
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of study drug to minimize the risk of pregnancy. WOCBP must have a negative serum or urine pregnancy test within 72 hours before the start of the investigational product.
Who cannot join
- Women who are pregnant or breastfeeding.
- Patients with brain metastases.
- Patients with resectable colorectal cancer or non-adenocarcinoma cancer of the colon or rectum.
- Patients who have had prior therapy with brivanib, anti-PDGFR (platelet-derived growth factor receptor) or anti-FGFR (fibroblast growth factor receptor) therapy.
- Recent (within 4 weeks of the first study drug administration), or planned participation in another experimental therapeutic drug study.
- Recent (within 4 weeks of the first study drug administration) infusion of bevacizumab therapy.
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- Prior irinotecan chemotherapy.
- Prior full field radiotherapy =/<4 weeks or limited field radiotherapy =/<2 weeks prior to first study drug administration.
- Recent use (within 4 weeks of first study drug administration) of St. John's Wort.
- Patients with a history of thrombotic or embolic events within the last six months such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism.
- Patients with gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE (version 4.0) Grade 4 within 30 days prior to first study drug administration
- Patients with uncontrolled or significant cardiovascular disease including: i) Active coronary artery disease, unstable or newly diagnosed angina or myocardial infarction < 12 months prior to first study drug administration. ii) Class III-IV New York Heart Association (NYHA) congestive heart failure. iii) Uncontrolled hypertension (Systolic blood pressure [BP] > 150 mmHg and diastolic BP > 90 mmHg for 24 hours) despite optimal medical management. Blood pressure must be below 140/90 mmHg at screening. Subjects with a history of hypertension who are receiving treatment with calcium channel blockers that are CYP3A4 substrates should be changed to an alternative antihypertensive medication prior to first study drug administration. iv) Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin. v) QTc (Fridericia) prolongation >450 msec. vi) Subjects with valvular heart disease =/> CTCAE (Ver. 4.0) Gr 2. vii) Left ventricular ejection fraction (LVEF) < 50%.
- Active infection, less than 7 days after completing systemic antibiotic therapy.
- History of non-healing wounds or ulcers, or bone fractures within 3 months prior to first study drug administration.
- Major surgical procedure, open biopsy, or significant traumatic injury less than 3 weeks or those who receive minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 1 week from first dose of first study drug administration.
- Inability to swallow tablets or untreated malabsorption syndrome.
- Pre-existing thyroid abnormality with thyroid function that can not be maintained in the normal range with medication.
- History of human immunodeficiency virus (HIV).
- Patients with centrally cavitating lung lesions.
- Known bleeding diathesis.
- Inability to comply with study and/or follow-up procedures.
- Patients with known glomerular nephritis.
- Patients with known polycythemia.
- Patients with known Gilbert's syndrome.
- Women with a positive pregnancy test.
- Patients with hyponatremia (sodium < 130 mmol/L).
- Baseline serum potassium < 3.5 mmol/L (potassium supplementation may be given to restore the serum potassium above this level prior to study entry).
- Baseline serum calcium < 8.4 mg/dL (calcium supplementation may be given to restore the serum calcium above this level prior to study entry).
- Baseline serum magnesium < 1.5 mg/dL (magnesium supplementation may be given to restore the serum magnesium above this level prior to study entry).
- Known or suspected history of allergy to brivanib or any agents given in association with this study.
- Prisoners or subjects who are involuntarily incarcerated. Patients who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study of Second-line Irinotecan Plus Brivanib, a Dual Tyrosine Inhibitor of VEGFR and FGFR, in Metastatic Colorectal Cancer Patients Enriched for Elevated Levels of Plasma FGF Following Progression on Bevacizumab-based Treatment
The goal of this clinical research study is to learn if adding brivanib to irinotecan can help control the disease in patients with colorectal cancer that has spread. The safety of this drug combination will also be studied.
Read the detailed description
Study Drugs:
Brivanib is designed to keep cancer cells from receiving the blood supply they need. This may slow down the growth of cancer cells.
Irinotecan is designed to interfere with the DNA (genetic material) of cancer cells. This may slow down the growth and spread of cancer cells.
Study Drug Administration:
If you are found to be eligible to take part in this study, you will take brivanib by mouth 1 time every day. The study drug should be taken at the same time each day with a glass (about 8 ounces) of water. You can take it with or without food.
You will be given irinotecan by vein over about 1½ hours on Day 1 of each 14-day cycle. You may be given other drugs to help prevent side effects. The study staff will tell you about these drugs, how they will be given, and the possible risks.
If you have a side effect, you should tell your doctor or study nurse right away. Your study doctor may prescribe drugs for your side effects, delay future treatments, lower the dose of the study drugs, or stop your treatment with the study drugs.
Study Visits:
On Day 7 of Cycle 1:
- Your vital signs will be measured.
- Blood (about 2 tablespoons) will be drawn for routine tests and to check your thyroid function. If the doctor thinks it is needed, part of the blood may be used to check your blood's ability to clot.
Before all cycles, starting with Cycle 2:
- You will have a physical exam, including measurement of your vital signs.
- Your performance status will be recorded.
- Blood (about 1-2 tablespoons) will be collected for routine tests. If the doctor thinks it is needed, part of the blood may be used to check your blood's ability to clot if needed.
- You will be asked about any drugs you may have taken and side effects you may have had.
- Before Cycles 2 and 3 only, blood (about 1 tablespoon) will be drawn to check your thyroid function.
Every 8 weeks:
- You will have a CT scan or MRI scan to check the status of the disease.
- Blood (about 2-3 tablespoons) will be drawn for thyroid, CEA, and cytokine testing.
- Urine will be collected for routine tests.
Every 12 weeks (Weeks 12, 24, 36, and so on), you will have an ECHO to check your heart function.
Length of Study:
You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse or intolerable side effects occur.
End-of-Treatment Visit:
Within 2 weeks after you stop taking the study drugs, the following tests and procedures will be performed if not done in the last 14 days:
- You will be asked about any side effects you may have had and any drugs you may be taking.
- You will have a physical exam, including measurement of your vital signs.
- Your performance status will be recorded.
- You will have a CT scan or MRI scan to check the status of the disease.
- Blood (about 1-2 tablespoons) and urine will be collected for routine tests.
- Blood (about 2-3 tablespoons) will be drawn for thyroid, CEA, and cytokine testing.
Long-Term Follow-Up:
After you stop taking the study drugs, you will be called every 3 months. You will be asked questions about your health. These calls should last about 15 minutes each time.
This is an investigational study. Brivanib is not FDA approved or commercially available. It is currently being used for research purposes only. Irinotecan is FDA approved and commercially available for the treatment of colorectal cancer. The combination of brivanib and irinotecan is considered investigational.
Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.
- Conditions
- Colorectal Cancer, Colorectal Adenocarcinoma
- Being tested
- Brivanib, Irinotecan
- Keywords
- colon, Colorectum, Colorectal Cancer, Plasma FGF, Colorectal adenocarcinoma, Bevacizumab, Brivanib, BMS-582664, Irinotecan, CPT-11, Camptosar, Fibroblast Growth Factor, bFGF, tyrosine kinase receptors, vascular endothelial growth factor receptors, VEGFR, fibroblast growth factor receptors, FGFR
- Medical subject headings
- Colorectal Neoplasms, Acrocephalosyndactylia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrivanibDrug
Also called BMS-582664
800 mg (4 x 200 mg tablets) self-administered orally at approximate same time each day on a continuous daily schedule Days 1-14 of 14 day cycle.
IrinotecanDrug
Also called CPT-11, Camptosar
180 mg/m^2 by vein on Day 1 of a 14 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Brivanib + Irinotecan | Experimental | Brivanib 800 mg orally daily Days 1-14, and Irinotecan intravenously 180 mg/m^2 on Day 1. Receives: Drug: Brivanib; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Median Progression-Free Survival (PFS)
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: Enrollment (baseline) to disease progression or death, followed each 14 day treatment then every 2 months,up to 100 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2011 (estimated)
- Study startAug 2011
- Primary completionNov 2013
- Study completionNov 2013
Why it stopped: Sponsor closed study
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.
- More trials run by M.D. Anderson Cancer CenterThe 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
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Michael Overman, MD, Principal investigator, UT MD Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01367275
- Sponsor's protocol ID
- 2010-0378
- Status last verified
- Sep 2020
- First submitted
- 3 Jun 2011
- Last updated
- 3 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Second-line Irinotecan Plus Brivanib, a Dual Tyrosine Inhibitor of VEGFR and FGFR, in Metastatic Colorectal Cancer Patients Enriched for Elevated Levels of Plasma FGF Following Progression on Bevacizumab-based Treatment
- ClinicalTrials.gov ID
- NCT01367275
- Acronym / sponsor ID
- 2010-0378
- Conditions
- Colorectal Cancer, Colorectal Adenocarcinoma
- Keywords
- colon, Colorectum, Colorectal Cancer, Plasma FGF, Colorectal adenocarcinoma, Bevacizumab, Brivanib, BMS-582664
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor closed study
- Enrolment
- 8 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Aug 2011
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 7 Jun 2011 (estimated)
- Results
- Posted 3 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to learn if adding brivanib to irinotecan can help control the disease in patients with colorectal cancer that has spread. The safety of this drug combination will also be studied.
Detailed description
Study Drugs:
Brivanib is designed to keep cancer cells from receiving the blood supply they need. This may slow down the growth of cancer cells.
Irinotecan is designed to interfere with the DNA (genetic material) of cancer cells. This may slow down the growth and spread of cancer cells.
Study Drug Administration:
If you are found to be eligible to take part in this study, you will take brivanib by mouth 1 time every day. The study drug should be taken at the same time each day with a glass (about 8 ounces) of water. You can take it with or without food.
You will be given irinotecan by vein over about 1½ hours on Day 1 of each 14-day cycle. You may be given other drugs to help prevent side effects. The study staff will tell you about these drugs, how they will be given, and the possible risks.
If you have a side effect, you should tell your doctor or study nurse right away. Your study doctor may prescribe drugs for your side effects, delay future treatments, lower the dose of the study drugs, or stop your treatment with the study drugs.
Study Visits:
On Day 7 of Cycle 1:
- Your vital signs will be measured.
- Blood (about 2 tablespoons) will be drawn for routine tests and to check your thyroid function. If the doctor thinks it is needed, part of the blood may be used to check your blood's ability to clot.
Before all cycles, starting with Cycle 2:
- You will have a physical exam, including measurement of your vital signs.
- Your performance status will be recorded.
- Blood (about 1-2 tablespoons) will be collected for routine tests. If the doctor thinks it is needed, part of the blood may be used to check your blood's ability to clot if needed.
- You will be asked about any drugs you may have taken and side effects you may have had.
- Before Cycles 2 and 3 only, blood (about 1 tablespoon) will be drawn to check your thyroid function.
Every 8 weeks:
- You will have a CT scan or MRI scan to check the status of the disease.
- Blood (about 2-3 tablespoons) will be drawn for thyroid, CEA, and cytokine testing.
- Urine will be collected for routine tests.
Every 12 weeks (Weeks 12, 24, 36, and so on), you will have an ECHO to check your heart function.
Length of Study:
You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse or intolerable side effects occur.
End-of-Treatment Visit:
Within 2 weeks after you stop taking the study drugs, the following tests and procedures will be performed if not done in the last 14 days:
- You will be asked about any side effects you may have had and any drugs you may be taking.
- You will have a physical exam, including measurement of your vital signs.
- Your performance status will be recorded.
- You will have a CT scan or MRI scan to check the status of the disease.
- Blood (about 1-2 tablespoons) and urine will be collected for routine tests.
- Blood (about 2-3 tablespoons) will be drawn for thyroid, CEA, and cytokine testing.
Long-Term Follow-Up:
After you stop taking the study drugs, you will be called every 3 months. You will be asked questions about your health. These calls should last about 15 minutes each time.
This is an investigational study. Brivanib is not FDA approved or commercially available. It is currently being used for research purposes only. Irinotecan is FDA approved and commercially available for the treatment of colorectal cancer. The combination of brivanib and irinotecan is considered investigational.
Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Brivanib + Irinotecan | Experimental | Drug: Brivanib, Drug: IrinotecanBrivanib 800 mg orally daily Days 1-14, and Irinotecan intravenously 180 mg/m^2 on Day 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Signed written Informed Consent.
- Patient must have progressed on front-line chemotherapy treatment containing bevacizumab for histologically confirmed colorectal adenocarcinoma that is unresectable or metastatic. Progression is defined as either radiographic or clinical progression.
- Patient must have measurable lesions as defined by RECIST version 1.1 criteria.
- ECOG performance status 0-2.
- Known bFGF level performed by a CLIA-certified laboratory performed during or within 12 weeks of last bevacizumab treatment
Key exclusion criteria (31 listed)
- Women who are pregnant or breastfeeding.
- Patients with brain metastases.
- Patients with resectable colorectal cancer or non-adenocarcinoma cancer of the colon or rectum.
- Patients who have had prior therapy with brivanib, anti-PDGFR (platelet-derived growth factor receptor) or anti-FGFR (fibroblast growth factor receptor) therapy.
- Recent (within 4 weeks of the first study drug administration), or planned participation in another experimental therapeutic drug study.
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 |
|---|---|---|
| BrivanibAlso: BMS-582664800 mg (4 x 200 mg tablets) self-administered orally at approximate same time each day on a continuous daily schedule Days 1-14 of 14 day cycle. | Drug | Brivanib + Irinotecan |
| IrinotecanAlso: CPT-11, Camptosar180 mg/m^2 by vein on Day 1 of a 14 day cycle. | Drug | Brivanib + Irinotecan |
Primary outcome
Number of Participants With Median Progression-Free Survival (PFS)
Time frame: Enrollment (baseline) to disease progression or death, followed each 14 day treatment then every 2 months,up to 100 week
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- UT MD Anderson WebsiteLink provided by the sponsor.
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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.
Michael Overman, MD principal investigator
UT MD Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Brivanib and Irinotecan in people with Colorectal Cancer and Colorectal Adenocarcinoma, run by M.D. Anderson Cancer Center 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 14 inclusion and 31 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 3 Sep 2020. 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 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 3 Sep 2020). 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?
Number of Participants With Median Progression-Free Survival (PFS) (time frame: Enrollment (baseline) to disease progression or death, followed each 14 day treatment then every 2 months,up to 100 week). 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 3 Sep 2020.