Advanced CancerPhase 1NCT00940381
Sirolimus and Cetuximab in Advanced Malignancies
A Phase 1 study testing Sirolimus and Cetuximab in people with Advanced Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to find the highest tolerable dose of the combination of sirolimus and cetuximab that can be given to patients with advanced cancer. 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
- Advanced Cancer
- What is being tested?
- Sirolimus and Cetuximab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 165 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2009to May 2014
- 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
- Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months.
- Patients must be >/= 3 weeks beyond treatment with a cytotoxic chemotherapy regimen, or therapeutic radiation, or major surgery. Patients may have received palliative localized radiation immediately before or during treatment providing radiation is not delivered to the only site of disease being treated under this protocol. For biologic/targeted agents patients must be >/= 5 half-lives or >/= 3 weeks form the last dose (whichever comes first).
- Eastern Cooperative Oncology Group (ECOG) performance status </= 3.
- Patients must have normal organ and marrow function defined as: absolute neutrophil count >/= 1,000/mL; platelets >/=50,000/mL; creatinine </= 3 X upper limit of normal (ULN); total bilirubin </= 2.0; ALT(SGPT) </= 5 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; ALT(SGPT) </= 8 X ULN; cholesterol </= 350 mg/dL; triglycerides </= 400 mg/dL.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose.
- Patients with colorectal cancer with Kirsten rat sarcoma (kRAS) mutations (mutational status must be available prior to entering the study)
- Patients must be able to understand and be willing to sign a written informed consent document.
Who cannot join
- Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
- Pregnant or lactating women.
- History of hypersensitivity to cetuximab, murine products, or any component of the formulation.
- History of hypersensitivity to sirolimus.
- History of hypersensitivity to any component of the formulation.
- Patients with colorectal cancer with kRAS mutations. (mutational status must be available prior to entering the study)
- Patients unwilling or unable to sign informed consent document.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Trial of Sirolimus and Cetuximab in Patients With Advanced Malignancies
The goal of this clinical research study is to find the highest tolerable dose of the combination of sirolimus and cetuximab that can be given to patients with advanced cancer. The safety of this drug combination will also be studied.
Read the detailed description
The Study Drugs:
Cetuximab is designed to prevent or slow down the growth of cancer cells by blocking protein on the surface of the cancer cell, called the epidermal growth factor receptor (EGFR).
Sirolimus is designed to block a protein called mTOR inside the cancer cell. This may interfere with the growth or spread of cancer cells or possibly kill the cancer cells.
Study Drug Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of cetuximab and sirolimus based on when you joined this study. Up to 9 dose levels of cetuximab and sirolimus will be tested. Three (3) to 9 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the combination of cetuximab and sirolimus is found.
Once the highest tolerated dose of the combination of cetuximab and sirolimus is found, 2 groups of additional participants (Group 1 and Group 2, each of 14 participants) will be enrolled and receive the study drugs at that dose level. Another 14 participants with the non-small lung and head and neck cancer will receive the study drug at that dose level, as well.
Study Drug Administration:
Each study "cycle" is 28 days.
Everyday, you will take sirolimus by mouth 1 time a day. You should take it at about the same time each day with food and a cup of water.
On Days 1, 8, 15, and 22 of each cycle, you will receive cetuximab by vein over 2 hours. If the first dose is well tolerated, you will receive the next dose over 1 hour.
Study Visits:
At every study visit, you will be asked about any current health conditions you have, drugs you are taking, and if you have experienced any side effects.
Between Days 8 and 15 of Cycle 1, the following tests and procedures will be performed:
-If you are enrolled in a Group 2 of the highest drug combination dose, you will have a tumor biopsy and your blood (about 1-3 tablespoons) will be drawn for pharmacodynamic (PD) testing.
About Days 8 and 22 of Cycle 1, the following tests and procedures will be performed:
- You will have a physical exam.
- Blood (about 2 teaspoons) will be drawn for routine tests.
About Day 15 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests.
About Day 22 of Cycles 2 and then every 1-2 cycles, the following tests and procedures will be performed:
- You will have a physical exam.
- Blood (about 2 teaspoons) will be drawn for routine tests.
Every 4 weeks, you will have a blood (about 1 teaspoon) drawn or urine collected for pregnancy test if you are able to become pregnant.
Every 8 weeks, you will have an x-ray, CT scan, MRI, and/or PET/CT to check the status of the disease. The study doctor thinks it is needed, they will be performed more often.
Length of Study:
You may stay on study for as long as you are benefitting. You will be taken off study if you experience intolerable side effects, the study doctor thinks it is in your best interest, or the cancer gets worse.
End-of-Study Visit:
About 28 days after the last dose of study drugs, you will have an end-of-study visit. At this visit, the following tests or procedures may be performed:
- You will have a physical exam, including measurement of your vital signs.
- Your performance status will be recorded.
- Blood (about 2 teaspoons) will be drawn for routine tests.
- If the doctor thinks it is needed, you will have an x-ray, CT, MRI, and/or PET/CT to check the status of the disease.
This is an investigational study. Sirolimus is FDA approved and commercially available as an anti-rejection drug for kidney transplant recipients. Cetuximab is FDA approved and commercially available for the treatment of colorectal and head/neck cancers. The combination of these drugs is investigational.
Up to 137 patients will take part in this study. All will be enrolled at MD Anderson.
- Conditions
- Advanced Cancer
- Keywords
- Advanced Malignancies, Sirolimus, Rapamune, Cetuximab, C225, Erbitux, IMC-225
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamune
Beginning dose 3 mg by mouth on Day 1, and 1 mg on Days 2 - 28 for a 28 day cycle.
CetuximabDrug
Also called C225, Erbitux, IMC-225
Beginning dose 100 mg/m^2 by vein over two hours on Day 1, and 65 mg/m^2 on Days 8, 15 and 22 for a 28 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus + Cetuximab | Experimental | Sirolimus beginning dose 3 mg by mouth on Day 1, and 1 mg on Days 2 - 28 for a 28 day cycle. Cetuximab Beginning dose 100 mg/m^2 by vein over two hours on Day 1, and 65 mg/m^2 on Days 8, 15 and 22 for a 28 day cycle. Receives: Drug: Sirolimus; Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicities (DLT) of Combination Treatment with Sirolimus and Cetuximab
MTD defined by DLTs that occur in the first cycle (4 weeks). DLT defined as any clinically grade 3 or 4 non-hematologic toxicity as defined in the NCI CTC v3.0, expected and believed to be related to the study medications (except nausea and vomiting, electrolyte imbalances responsive to appropriate regimens or alopecia), any grade 4 hematologic toxicity lasting at least 3 weeks or longer (as defined by the NCI-CTC v3.0) or associated with bleeding and/or sepsis; any grade 4 nausea or vomiting > 5 days despite maximum anti-nausea regimens, and any other grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in the NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 that is attributable to therapy.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2009 (estimated)
- Study startJul 2009
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 165 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Filip Janku, MD,PHD, Principal investigator, UT MD Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00940381
- Sponsor's protocol ID
- 2009-0226
- Other IDs
- NCI-2012-01271
- Status last verified
- May 2014
- First submitted
- 14 Jul 2009
- Last updated
- 18 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Sirolimus and Cetuximab in Patients With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT00940381
- Acronym / sponsor ID
- 2009-0226
- Conditions
- Advanced Cancer
- Keywords
- Advanced Malignancies, Sirolimus, Rapamune, Cetuximab, C225, Erbitux, IMC-225
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 165 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Jul 2009
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 16 Jul 2009 (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 goal of this clinical research study is to find the highest tolerable dose of the combination of sirolimus and cetuximab that can be given to patients with advanced cancer. The safety of this drug combination will also be studied.
Detailed description
The Study Drugs:
Cetuximab is designed to prevent or slow down the growth of cancer cells by blocking protein on the surface of the cancer cell, called the epidermal growth factor receptor (EGFR).
Sirolimus is designed to block a protein called mTOR inside the cancer cell. This may interfere with the growth or spread of cancer cells or possibly kill the cancer cells.
Study Drug Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of cetuximab and sirolimus based on when you joined this study. Up to 9 dose levels of cetuximab and sirolimus will be tested. Three (3) to 9 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the combination of cetuximab and sirolimus is found.
Once the highest tolerated dose of the combination of cetuximab and sirolimus is found, 2 groups of additional participants (Group 1 and Group 2, each of 14 participants) will be enrolled and receive the study drugs at that dose level. Another 14 participants with the non-small lung and head and neck cancer will receive the study drug at that dose level, as well.
Study Drug Administration:
Each study "cycle" is 28 days.
Everyday, you will take sirolimus by mouth 1 time a day. You should take it at about the same time each day with food and a cup of water.
On Days 1, 8, 15, and 22 of each cycle, you will receive cetuximab by vein over 2 hours. If the first dose is well tolerated, you will receive the next dose over 1 hour.
Study Visits:
At every study visit, you will be asked about any current health conditions you have, drugs you are taking, and if you have experienced any side effects.
Between Days 8 and 15 of Cycle 1, the following tests and procedures will be performed:
-If you are enrolled in a Group 2 of the highest drug combination dose, you will have a tumor biopsy and your blood (about 1-3 tablespoons) will be drawn for pharmacodynamic (PD) testing.
About Days 8 and 22 of Cycle 1, the following tests and procedures will be performed:
- You will have a physical exam.
- Blood (about 2 teaspoons) will be drawn for routine tests.
About Day 15 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests.
About Day 22 of Cycles 2 and then every 1-2 cycles, the following tests and procedures will be performed:
- You will have a physical exam.
- Blood (about 2 teaspoons) will be drawn for routine tests.
Every 4 weeks, you will have a blood (about 1 teaspoon) drawn or urine collected for pregnancy test if you are able to become pregnant.
Every 8 weeks, you will have an x-ray, CT scan, MRI, and/or PET/CT to check the status of the disease. The study doctor thinks it is needed, they will be performed more often.
Length of Study:
You may stay on study for as long as you are benefitting. You will be taken off study if you experience intolerable side effects, the study doctor thinks it is in your best interest, or the cancer gets worse.
End-of-Study Visit:
About 28 days after the last dose of study drugs, you will have an end-of-study visit. At this visit, the following tests or procedures may be performed:
- You will have a physical exam, including measurement of your vital signs.
- Your performance status will be recorded.
- Blood (about 2 teaspoons) will be drawn for routine tests.
- If the doctor thinks it is needed, you will have an x-ray, CT, MRI, and/or PET/CT to check the status of the disease.
This is an investigational study. Sirolimus is FDA approved and commercially available as an anti-rejection drug for kidney transplant recipients. Cetuximab is FDA approved and commercially available for the treatment of colorectal and head/neck cancers. The combination of these drugs is investigational.
Up to 137 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 |
|---|---|---|
| Sirolimus + Cetuximab | Experimental | Drug: Sirolimus, Drug: CetuximabSirolimus beginning dose 3 mg by mouth on Day 1, and 1 mg on Days 2 - 28 for a 28 day cycle. Cetuximab Beginning dose 100 mg/m^2 by vein over two hours on Day 1, and 65 mg/m^2 on Days 8, 15 and 22 for a 28 day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months.
- Patients must be >/= 3 weeks beyond treatment with a cytotoxic chemotherapy regimen, or therapeutic radiation, or major surgery. Patients may have received palliative localized radiation immediately before or during treatment providing radiation is not delivered to the only site of disease being treated under this protocol. For biologic/targeted agents patients must be >/= 5 half-lives or >/= 3 weeks form the last dose (whichever comes first).
- Eastern Cooperative Oncology Group (ECOG) performance status </= 3.
- Patients must have normal organ and marrow function defined as: absolute neutrophil count >/= 1,000/mL; platelets >/=50,000/mL; creatinine </= 3 X upper limit of normal (ULN); total bilirubin </= 2.0; ALT(SGPT) </= 5 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; ALT(SGPT) </= 8 X ULN; cholesterol </= 350 mg/dL; triglycerides </= 400 mg/dL.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose.
Key exclusion criteria (7 listed)
- Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support.
- Pregnant or lactating women.
- History of hypersensitivity to cetuximab, murine products, or any component of the formulation.
- History of hypersensitivity to sirolimus.
- History of hypersensitivity to any component of the formulation.
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 |
|---|---|---|
| SirolimusAlso: RapamuneBeginning dose 3 mg by mouth on Day 1, and 1 mg on Days 2 - 28 for a 28 day cycle. | Drug | Sirolimus + Cetuximab |
| CetuximabAlso: C225, Erbitux, IMC-225Beginning dose 100 mg/m^2 by vein over two hours on Day 1, and 65 mg/m^2 on Days 8, 15 and 22 for a 28 day cycle. | Drug | Sirolimus + Cetuximab |
Primary outcome
Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicities (DLT) of Combination Treatment with Sirolimus and Cetuximab
Time frame: 4 weeks
MTD defined by DLTs that occur in the first cycle (4 weeks). DLT defined as any clinically grade 3 or 4 non-hematologic toxicity as defined in the NCI CTC v3.0, expected and believed to be related to the study medications (except nausea and vomiting, electrolyte imbalances responsive to appropriate regimens or alopecia), any grade 4 hematologic toxicity lasting at least 3 weeks or longer (as defined by the NCI-CTC v3.0) or associated with bleeding and/or sepsis; any grade 4 nausea or vomiting > 5 days despite maximum anti-nausea regimens, and any other grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in the NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0 that is attributable to therapy.
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 18 Nov 2015.
- University of Texas MD Anderson Cancer Center 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.
Filip Janku, MD,PHD 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 1 study testing Sirolimus and Cetuximab in people with Advanced Cancer, 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 7 inclusion and 7 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 18 Nov 2015. 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) and Dose-Limiting Toxicities (DLT) of Combination Treatment with Sirolimus and Cetuximab (time frame: 4 weeks). 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 18 Nov 2015.