Advanced CancerPhase 1NCT00543504
Bevacizumab in Multiple Phase I Combinations
A Phase 1 study testing Bevacizumab, Sorafenib and Erlotinib 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 Avastin™ that can be given in combination with 4 other study drug/drug combinations. It will be given with sunitinib, with sorafenib, with a combination of erlotinib and cetuximab, and with a combination of trastuzumab and lapatinib. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Advanced Cancer
- What is being tested?
- Bevacizumab, Sorafenib and Erlotinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 343 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Oct 2007to 29 Apr 2020
- 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 Any age
- All sexes
- No healthy volunteers
- Child, 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 have no standard therapy that induces a CR rate of at least 10% or improves survival by at least three months.
- Patients must be three weeks from prior cytotoxic therapy; if they have recovered their blood counts to eligibility levels sooner and have no mucositis or other acute toxicities, they may be treated earlier but no sooner than two weeks after their last chemotherapy. Patients must be two weeks or five half lives from biologic therapy, whichever is shorter.
- ECOG performance status </= 2 (Karnofsky >/= 60%).
- Patients must have normal organ and marrow function defined as: absolute neutrophil count >/= 1,000/mL; platelets >/=75,000/mL; creatinine </= 3 X ULN; total bilirubin </= 2.0; ALT(SGPT) </= 3 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; ALT(SGPT) </= 5 X ULN. Exception for the bevacizumab + erlotinib + cetuximab arm and the bevacizumab + trastuzumab + lapatinib arm: no minimum absolute neutrophil count or platelet count.
- The effects of bevacizumab on the developing human fetus are unknown. Angiogenesis is of critical importance to fetal development, and bevacizumab is likely to have adverse consequences in terms of fetal development. For this reason, 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.
- Ability to understand and the willingness to sign a written informed consent document.
- Life expectancy of at least 3 months.
- Patients with a prior DVT/PE are eligible for treatment if they are receiving or have finished receiving appropriate anticoagulation therapy.
Who cannot join
- Patients with hemoptysis within 28 days prior to entering the study.
- Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
- Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg on medication).
- Patients with clinically significant cardiovascular disease: history of CVA within 6 months, myocardial infarction or unstable angina within 6 months, or unstable angina pectoris.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 1.
- Pregnant or lactating women.
Show all 18Show fewer
- History of hypersensitivity to bevacizumab, murine products, or any component of the formulation.
- (For patients on the sunitinib treatment arm and the trastuzumab/lapatinib treatment arm only) Left ventricular ejection fraction of less than 50% unless the patient is receiving an angiotensin-converting enzyme (ACE) inhibitor / angiotensin receptor blocker (ARB) and a beta-blocker.
- (For sorafenib treatment arm only) Hypersensitivity to sorafenib or any component of the formulation.
- (For erlotinib and cetuximab treatment arm only) History of hypersensitivity to erlotinib or any component of the formulation.
- (For erlotinib and cetuximab treatment arm only) History of hypersensitivity to cetuximab, murine products, or any component of the formulation.
- (For trastuzumab and lapatinib treatment arm only) History of hypersensitivity to trastuzumab, Chinese hamster ovary cell proteins, or any component of the formulation.
- (For trastuzumab and lapatinib treatment arm only) History of hypersensitivity to lapatinib or any component of the formulation.
- Patients with clinically significant gastrointestinal bleeding within 28 days prior to entering the study.
- Patients with hemorrhagic brain metastases.
- Patients with prior abdominal surgery within 30 days prior to entering the study.
- (For patients on the sunitinib treatment arm and the trastuzumab/lapatinib treatment arm only) Left ventricular ejection fraction of less than 50%, unless the patient is receiving an angiotensin-converting enzyme (ACE) inhibitor / angiotensin receptor blocker (ARB) and a beta-blocker.
- (For patients on the sunitinib treatment arm and the trastuzumab/lapatinib treatment arm only) QTc prolongation, defined as greater than 440 milliseconds for males, and greater than 460 milliseconds for females.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Phase 1 Study of Bevacizumab in Combination With 1) Sunitinib, 2) Sorafenib, 3) Erlotinib and Cetuximab, 4) Trastuzumab and Lapatinib
The goal of this clinical research study is to find the highest tolerable dose of Avastin™ that can be given in combination with 4 other study drug/drug combinations. It will be given with sunitinib, with sorafenib, with a combination of erlotinib and cetuximab, and with a combination of trastuzumab and lapatinib. The safety and effectiveness of these drug combinations will also be studied.
Read the detailed description
The Study Drugs:
Bevacizumab (Avastin™) is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels
Sunitinib malate (SutentTM) is designed to block pathways that control important events such as the growth of blood vessels that are vital for the growth of cancer.
Sorafenib (NexavarTM) is designed to block the function of important proteins in cancer cells. These proteins, when active, are in part responsible for the abnormal growth and behavior of cancer cells.
Erlotinib hydrochloride (TarcevaTM) is designed to block the activity of a protein found on the surface of many tumor cells that may control tumor growth and survival. This may stop tumors from growing.
Cetuximab (ErbituxTM) is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell, called the epidermal growth factor receptor (EGFR).
Trastuzumab (HerceptinTM) is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell, called the Her2/neu receptor.
Lapatinib (TykerbTM) is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell, called the Her2/neu receptor and EGFR.
Study Drug Dose Level:
If you are found to be eligible to take part in this study, your doctor will decide which study drugs you will receive based on the disease type and on the drugs you have taken in the past.
Once it is decided which drugs you will receive, you will be enrolled into a group of about 3-6 participants that are receiving the same drug combination. The first group of participants will receive the lowest dose of the drug combination. The next group of participants will receive the next highest dose of the drug combination. The third group will receive an even higher dose than that. This process will continue until the study doctor finds the highest safe dose of the drug combination. The dose that you receive will depend on when you are enrolled in this study and the safety data that is available at that time. The dose that you receive may be lowered if you do not tolerate the study drug combination well.
Once the highest tolerated dose is found for each group, up to 10 more participants will be added to each group at that dose level.
The dose levels testing the study drug combination of bevacizumab with either sunitinib or sorafenib are now closed.
Study Drug Administration:
Avastin™ is given through a needle in your vein. The first infusion is over 90 minutes. The next infusion may be over 60 minutes if the first infusion was well tolerated. If you tolerate the second infusion well, the third infusion may be over 30 minutes. If you take trastuzumab and lapatinib with Avastin™, you will receive Avastin™ every 21 days. If you take cetuximab and erlotinib with Avastin™, you will receive Avastin™ every 14 days.
If you are assigned to take cetuximab and erlotinib, cetuximab will be given by vein once every week. The first time you receive cetuximab, it will be given over 2 hours. All other infusions will be given over 60 minutes. Erlotinib is taken by mouth every day during the 28-day study cycle. You should take erlotinib on an empty stomach either 1 hour before eating or 2 hours after eating.
If you are assigned to take trastuzumab and lapatinib, trastuzumab will be given by vein once every 21-day study cycle. The first infusion will be over 90 minutes. If you handle the infusion well, each additional infusion will be over 30 minutes Lapatinib will be taken by mouth every day for 21 days. You should take lapatinib on an empty stomach either 1 hour before eating or 2 hours after eating.
Study Visits:
Avastin, cetuximab, and erlotinib:
During Cycle 1, you will have a study visit during Weeks 1 and 2. During Cycles 2 and beyond, you will have a study visit during Week 1. At these visits, you will have a physical exam, and blood (about 1 tablespoon) will be drawn for routine tests. If the routine urine test done at screening had abnormal results, urine may be collected for additional routine tests during the study. After 2 cycles, you will have the physical exam every 1-2 months.
Every week, you will have blood drawn (about 2 teaspoons) for routine tests.
During Week 1 of all cycles, you will have urine collected for routine tests.
After every 2 cycles, you will have a CT or MRI scan to check the status of the disease. After 6 months (6 cycles) of study drug treatment, you will have the CT or MRI scan every 2-4 cycles.
Avastin, trastuzumab, and lapatinib:
During Cycle 1, you will have a study visit during Weeks 1 and 2. During Cycles 2 and beyond, you will have a study visit during Week 1. At these visits, you will have a physical exam, and blood (about 1 tablespoon) will be drawn for routine tests. If the routine urine test done at screening had abnormal results, urine may be collected for additional routine tests during the study. After 2 cycles, you will have the physical exam every 1-2 months.
During Week 1 of all cycles, you will have urine collected for routine tests.
After every 2 cycles, you will have a CT or MRI scan to check the status of the disease. After 6 months (8 cycles) of study drug treatment, you will have the CT or MRI scan every 2-4 cycles.
Length of Study:
You may remain on study for as long as you are benefitting. You will be taken off study if the disease gets worse or intolerable side effects occur.
This is an investigational study. Avastin™, erlotinib, cetuximab, trastuzumab, and lapatinib are all FDA approved and commercially available. Avastin™ is FDA approved for the treatment of colorectal cancer and lung cancer. Erlotinib is FDA approved for the treatment of lung cancer and pancreatic cancer. Cetuximab is FDA approved for the treatment of colorectal cancer and cancer of the head and neck. Trastuzumab is FDA approved for the treatment of breast cancer. Lapatinib is FDA approved for the treatment of breast cancer. The use of these drugs together is investigational and authorized for use in research only.
Up to 354 patients will take part in this study. All will be enrolled at M. D. Anderson.
- Conditions
- Advanced Cancer
- Being tested
- Bevacizumab, Sorafenib, Erlotinib, Trastuzumab, Lapatinib
- Keywords
- Advanced Cancer, Bevacizumab, Avastin, Sorafenib, BAY 43-9006, Erlotinib, OSI-774, Tarceva, Trastuzumab, Herceptin, Sunitinib, SU011248, Sutent, Cetuximab, Lapatinib, Tykerb, Anti-VEGF monoclonal antibody, rhuMAb-VEGF, Erlotinib hydrochloride, GW572016
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF
2.5 mg/kg By Vein Over 90 Minutes.
SorafenibDrug
Also called BAY 43-9006
200 mg By Mouth Daily for 28 Days
ErlotinibDrug
Also called Erlotinib hydrochloride, OSI-774, Tarceva
50 mg By Mouth Daily for 28 Days.
TrastuzumabDrug
Also called Herceptin
Loading 2 mg/kg by vein then Maintenance 1 mg/kg by vein on Day 1
LapatinibDrug
Also called GW572016, Tykerb
250 mg By Mouth Daily for 21 Days.
SunitinibDrug
Also called Sunitinib Malate, SU011248, Sutent
12.5 mg orally daily for 4 weeks, then 2 weeks off.
CetuximabDrug
Loading 100 mg/m² by vein and Maintenance 75 mg/m² by vein on Days 1, 8, 15, 22
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab + Sunitinib | Experimental | Arm 1: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Sunitinib 12.5 mg orally daily for 4 weeks, then 2 weeks off. Receives: Drug: Bevacizumab; Drug: Sunitinib |
| Bevacizumab + Sorafenib | Experimental | Arm 2: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Sorafenib 200 mg by mouth daily for 28 Days Receives: Drug: Bevacizumab; Drug: Sorafenib |
| Bevacizumab + Erlotinib + Cetuximab | Experimental | Arm 3: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Erlotinib 50 mg By Mouth Daily for 28 Days + Cetuximab loading dose 100 mg/m² IV and maintenance 75 mg/m² on Days 1, 8, 15, 22. Receives: Drug: Bevacizumab; Drug: Erlotinib; Drug: Cetuximab |
| Bevacizumab + Trastuzumab + Lapatinib | Experimental | Arm 4: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Trastuzumab loading dose 2 mg/kg IV then maintenance dose 1 mg/kg IV on Day 1 + Lapatinib 250 mg By Mouth Daily for 21 Days. Receives: Drug: Bevacizumab; Drug: Trastuzumab; Drug: Lapatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerable Dose (MTD) of Avastin in combination with 4 other study drug/drug combinations
MTD defined by Dose Limiting Toxicity in first 28 day cycle (induction phase)
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2007 (estimated)
- Study start10 Oct 2007
- Primary completion29 Apr 2020
- Study completion29 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 343 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Funda Meric-Bernstam, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00543504
- Sponsor's protocol ID
- 2006-0638
- Other IDs
- NCI-2012-01552
- Status last verified
- Jan 2020
- First submitted
- 11 Oct 2007
- Last updated
- 30 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Subbiah V, Dumbrava EI, Jiang Y, Thein KZ, Naing A, Hong DS, Fu S, Piha-Paul SA, Tsimberidou AM, Janku F, Meric-Bernstam F, Kurzrock R, Falchook G. Dual EGFR blockade with cetuximab and erlotinib combined with anti-VEGF antibody bevacizumab in advanced solid tumors: a phase 1 dose escalation triplet combination trial. Exp Hematol Oncol. 2020 Apr 20;9:7. doi: 10.1186/s40164-020-00159-1. eCollection 2020.
PubMed 32337094Falchook GS, Moulder SL, Wheler JJ, Jiang Y, Bastida CC, Kurzrock R. Dual HER2 inhibition in combination with anti-VEGF treatment is active in heavily pretreated HER2-positive breast cancer. Ann Oncol. 2013 Dec;24(12):3004-11. doi: 10.1093/annonc/mdt395. Epub 2013 Oct 24.
PubMed 24158411
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Bevacizumab in Combination With 1) Sunitinib, 2) Sorafenib, 3) Erlotinib and Cetuximab, 4) Trastuzumab and Lapatinib
- ClinicalTrials.gov ID
- NCT00543504
- Acronym / sponsor ID
- 2006-0638
- Conditions
- Advanced Cancer
- Keywords
- Advanced Cancer, Bevacizumab, Avastin, Sorafenib, BAY 43-9006, Erlotinib, OSI-774, Tarceva
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 343 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 10 Oct 2007 (actual)
- Primary completion
- 29 Apr 2020 (actual)
- Study completion
- 29 Apr 2020 (actual)
- First posted
- 15 Oct 2007 (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 Avastin™ that can be given in combination with 4 other study drug/drug combinations. It will be given with sunitinib, with sorafenib, with a combination of erlotinib and cetuximab, and with a combination of trastuzumab and lapatinib. The safety and effectiveness of these drug combinations will also be studied.
Detailed description
The Study Drugs:
Bevacizumab (Avastin™) is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels
Sunitinib malate (SutentTM) is designed to block pathways that control important events such as the growth of blood vessels that are vital for the growth of cancer.
Sorafenib (NexavarTM) is designed to block the function of important proteins in cancer cells. These proteins, when active, are in part responsible for the abnormal growth and behavior of cancer cells.
Erlotinib hydrochloride (TarcevaTM) is designed to block the activity of a protein found on the surface of many tumor cells that may control tumor growth and survival. This may stop tumors from growing.
Cetuximab (ErbituxTM) is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell, called the epidermal growth factor receptor (EGFR).
Trastuzumab (HerceptinTM) is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell, called the Her2/neu receptor.
Lapatinib (TykerbTM) is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell, called the Her2/neu receptor and EGFR.
Study Drug Dose Level:
If you are found to be eligible to take part in this study, your doctor will decide which study drugs you will receive based on the disease type and on the drugs you have taken in the past.
Once it is decided which drugs you will receive, you will be enrolled into a group of about 3-6 participants that are receiving the same drug combination. The first group of participants will receive the lowest dose of the drug combination. The next group of participants will receive the next highest dose of the drug combination. The third group will receive an even higher dose than that. This process will continue until the study doctor finds the highest safe dose of the drug combination. The dose that you receive will depend on when you are enrolled in this study and the safety data that is available at that time. The dose that you receive may be lowered if you do not tolerate the study drug combination well.
Once the highest tolerated dose is found for each group, up to 10 more participants will be added to each group at that dose level.
The dose levels testing the study drug combination of bevacizumab with either sunitinib or sorafenib are now closed.
Study Drug Administration:
Avastin™ is given through a needle in your vein. The first infusion is over 90 minutes. The next infusion may be over 60 minutes if the first infusion was well tolerated. If you tolerate the second infusion well, the third infusion may be over 30 minutes. If you take trastuzumab and lapatinib with Avastin™, you will receive Avastin™ every 21 days. If you take cetuximab and erlotinib with Avastin™, you will receive Avastin™ every 14 days.
If you are assigned to take cetuximab and erlotinib, cetuximab will be given by vein once every week. The first time you receive cetuximab, it will be given over 2 hours. All other infusions will be given over 60 minutes. Erlotinib is taken by mouth every day during the 28-day study cycle. You should take erlotinib on an empty stomach either 1 hour before eating or 2 hours after eating.
If you are assigned to take trastuzumab and lapatinib, trastuzumab will be given by vein once every 21-day study cycle. The first infusion will be over 90 minutes. If you handle the infusion well, each additional infusion will be over 30 minutes Lapatinib will be taken by mouth every day for 21 days. You should take lapatinib on an empty stomach either 1 hour before eating or 2 hours after eating.
Study Visits:
Avastin, cetuximab, and erlotinib:
During Cycle 1, you will have a study visit during Weeks 1 and 2. During Cycles 2 and beyond, you will have a study visit during Week 1. At these visits, you will have a physical exam, and blood (about 1 tablespoon) will be drawn for routine tests. If the routine urine test done at screening had abnormal results, urine may be collected for additional routine tests during the study. After 2 cycles, you will have the physical exam every 1-2 months.
Every week, you will have blood drawn (about 2 teaspoons) for routine tests.
During Week 1 of all cycles, you will have urine collected for routine tests.
After every 2 cycles, you will have a CT or MRI scan to check the status of the disease. After 6 months (6 cycles) of study drug treatment, you will have the CT or MRI scan every 2-4 cycles.
Avastin, trastuzumab, and lapatinib:
During Cycle 1, you will have a study visit during Weeks 1 and 2. During Cycles 2 and beyond, you will have a study visit during Week 1. At these visits, you will have a physical exam, and blood (about 1 tablespoon) will be drawn for routine tests. If the routine urine test done at screening had abnormal results, urine may be collected for additional routine tests during the study. After 2 cycles, you will have the physical exam every 1-2 months.
During Week 1 of all cycles, you will have urine collected for routine tests.
After every 2 cycles, you will have a CT or MRI scan to check the status of the disease. After 6 months (8 cycles) of study drug treatment, you will have the CT or MRI scan every 2-4 cycles.
Length of Study:
You may remain on study for as long as you are benefitting. You will be taken off study if the disease gets worse or intolerable side effects occur.
This is an investigational study. Avastin™, erlotinib, cetuximab, trastuzumab, and lapatinib are all FDA approved and commercially available. Avastin™ is FDA approved for the treatment of colorectal cancer and lung cancer. Erlotinib is FDA approved for the treatment of lung cancer and pancreatic cancer. Cetuximab is FDA approved for the treatment of colorectal cancer and cancer of the head and neck. Trastuzumab is FDA approved for the treatment of breast cancer. Lapatinib is FDA approved for the treatment of breast cancer. The use of these drugs together is investigational and authorized for use in research only.
Up to 354 patients will take part in this study. All will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab + Sunitinib | Experimental | Drug: Bevacizumab, Drug: SunitinibArm 1: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Sunitinib 12.5 mg orally daily for 4 weeks, then 2 weeks off. |
| Bevacizumab + Sorafenib | Experimental | Drug: Bevacizumab, Drug: SorafenibArm 2: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Sorafenib 200 mg by mouth daily for 28 Days |
| Bevacizumab + Erlotinib + Cetuximab | Experimental | Drug: Bevacizumab, Drug: Erlotinib, Drug: CetuximabArm 3: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Erlotinib 50 mg By Mouth Daily for 28 Days + Cetuximab loading dose 100 mg/m² IV and maintenance 75 mg/m² on Days 1, 8, 15, 22. |
| Bevacizumab + Trastuzumab + Lapatinib | Experimental | Drug: Bevacizumab, Drug: Trastuzumab, Drug: LapatinibArm 4: Bevacizumab starting dose 2.5 mg/kg intravenous (IV) over 90 minutes + Trastuzumab loading dose 2 mg/kg IV then maintenance dose 1 mg/kg IV on Day 1 + Lapatinib 250 mg By Mouth Daily for 21 Days. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or have no standard therapy that induces a CR rate of at least 10% or improves survival by at least three months.
- Patients must be three weeks from prior cytotoxic therapy; if they have recovered their blood counts to eligibility levels sooner and have no mucositis or other acute toxicities, they may be treated earlier but no sooner than two weeks after their last chemotherapy. Patients must be two weeks or five half lives from biologic therapy, whichever is shorter.
- ECOG performance status </= 2 (Karnofsky >/= 60%).
- Patients must have normal organ and marrow function defined as: absolute neutrophil count >/= 1,000/mL; platelets >/=75,000/mL; creatinine </= 3 X ULN; total bilirubin </= 2.0; ALT(SGPT) </= 3 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; ALT(SGPT) </= 5 X ULN. Exception for the bevacizumab + erlotinib + cetuximab arm and the bevacizumab + trastuzumab + lapatinib arm: no minimum absolute neutrophil count or platelet count.
- The effects of bevacizumab on the developing human fetus are unknown. Angiogenesis is of critical importance to fetal development, and bevacizumab is likely to have adverse consequences in terms of fetal development. For this reason, 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 (18 listed)
- Patients with hemoptysis within 28 days prior to entering the study.
- Patients with clinically significant unexplained bleeding within 28 days prior to entering the study.
- Uncontrolled systemic vascular hypertension (Systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg on medication).
- Patients with clinically significant cardiovascular disease: history of CVA within 6 months, myocardial infarction or unstable angina within 6 months, or unstable angina pectoris.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 1.
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 |
|---|---|---|
| BevacizumabAlso: Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF2.5 mg/kg By Vein Over 90 Minutes. | Drug | Bevacizumab + Erlotinib + Cetuximab, Bevacizumab + Sorafenib, Bevacizumab + Sunitinib, Bevacizumab + Trastuzumab + Lapatinib |
| SorafenibAlso: BAY 43-9006200 mg By Mouth Daily for 28 Days | Drug | Bevacizumab + Sorafenib |
| ErlotinibAlso: Erlotinib hydrochloride, OSI-774, Tarceva50 mg By Mouth Daily for 28 Days. | Drug | Bevacizumab + Erlotinib + Cetuximab |
| TrastuzumabAlso: HerceptinLoading 2 mg/kg by vein then Maintenance 1 mg/kg by vein on Day 1 | Drug | Bevacizumab + Trastuzumab + Lapatinib |
| LapatinibAlso: GW572016, Tykerb250 mg By Mouth Daily for 21 Days. | Drug | Bevacizumab + Trastuzumab + Lapatinib |
| SunitinibAlso: Sunitinib Malate, SU011248, Sutent12.5 mg orally daily for 4 weeks, then 2 weeks off. | Drug | Bevacizumab + Sunitinib |
| CetuximabLoading 100 mg/m² by vein and Maintenance 75 mg/m² by vein on Days 1, 8, 15, 22 | Drug | Bevacizumab + Erlotinib + Cetuximab |
Primary outcome
Maximum Tolerable Dose (MTD) of Avastin in combination with 4 other study drug/drug combinations
Time frame: 28 days
MTD defined by Dose Limiting Toxicity in first 28 day cycle (induction phase)
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 30 Jun 2020.
- Derived from this study: PubMed 32337094Subbiah V, Dumbrava EI, Jiang Y, Thein KZ, Naing A, Hong DS, Fu S, Piha-Paul SA, Tsimberidou AM, Janku F, Meric-Bernstam F, Kurzrock R, Falchook G. Dual EGFR blockade with cetuximab and erlotinib combined with anti-VEGF antibody bevacizumab in advanced solid tumors: a phase 1 dose escalation triplet combination trial. Exp Hematol Oncol. 2020 Apr 20;9:7. doi: 10.1186/s40164-020-00159-1. eCollection 2020.
- Derived from this study: PubMed 24158411Falchook GS, Moulder SL, Wheler JJ, Jiang Y, Bastida CC, Kurzrock R. Dual HER2 inhibition in combination with anti-VEGF treatment is active in heavily pretreated HER2-positive breast cancer. Ann Oncol. 2013 Dec;24(12):3004-11. doi: 10.1093/annonc/mdt395. Epub 2013 Oct 24.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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NAPOLI-2: Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Biliary Cancer
Advanced Biliary Tract Cancer
RecruitingPhase 3
Comparing Radiation Plus Cetuximab to Radiation Plus Chemotherapy in People With Advanced Head and Neck Cancer Who Cannot Receive Cisplatin
Locally Advanced Hypopharyngeal Squamous Cell Carcinoma, Locally Advanced Laryngeal Squamous Cell Carcinoma
Active, not recruitingPhase 1/2
A Study of Belzutifan (MK-6482) in Combination With Palbociclib Versus Belzutifan Monotherapy in Participants With Advanced Renal Cell Carcinoma (MK-6482-024/LITESPARK-024)
Renal Cell Carcinoma
Not yet recruitingPhase 2
Safety and Efficacy of Gemcitabine, Toripalimab and Dose- Modified Lenvatinib in Elderly Patients With Advanced Biliary Tract Cancer Intolerant to Conventional Chemotherapy
Advanced Biliary Tract Cancer
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.
Funda Meric-Bernstam, MD principal investigator
M.D. 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 Bevacizumab, Sorafenib and Erlotinib 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 8 inclusion and 18 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 30 Jun 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 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 Tolerable Dose (MTD) of Avastin in combination with 4 other study drug/drug combinations (time frame: 28 days). 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 NCT00543504, which also lists 2 linked publications.
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 30 Jun 2020.