Advanced CancerPhase 1NCT00895687
Study of Erlotinib in Combination With Bortezomib
A Phase 1 study testing Erlotinib Hydrochloride and Bortezomib 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 Tarceva (erlotinib hydrochloride) that can safely be given in combination with Velcade (bortezomib). The safety of this drug combination will also be studied. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Advanced Cancer
- What is being tested?
- Erlotinib Hydrochloride and Bortezomib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2009to Jul 2015
- 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 pathologically confirmed advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have had no standard therapy that induces a CR rate of at least 10% or improves survival by at least three months.
- Measurable or non-measurable disease.
- Patients must be >/= 6 wks beyond treatment with a nitrosourea or mitomycin-C, >/= 4 wks beyond other chemotherapy or external beam radiation therapy (XRT), and must have recovered to </= Grade 1 toxicity for any treatment-limiting toxicity resulting from prior therapy. (Exception: patients may have received palliative low dose XRT one week before treatment provided it is not given to the only targeted lesions).
- (continued from above) Also, patients who have received non-chemotherapeutic biological agents will need to wait at least 5 half-lives or 4 wks, whichever is shorter, from the last day of treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status </= 2 (Karnofsky >/= 60%)
- Patients must have normal organ and marrow function defined as: absolute neutrophil count >/=1,000/mL; platelets >/=50,000/mL; creatinine </= 2 X upper limit of normal (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.
Show all 9Show fewer
- Women of childbearing 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
- For the MTD expansion cohort, patients will be eligible if they meet one of the following criteria: (I) Have an EGFR-sensitive mutation and have been previously treated with EGFR inhibitor therapy but have subsequently developed resistance, OR (II) Have an EGFR-resistant mutation, OR (III) Do not have an EGFR mutation, but have benefited from EGFR inhibitor therapy (including either >/=4 months of stable disease [SD] OR a >/= partial response [PR]).
Who cannot join
- Patients with uncontrolled concurrent illness, including but not limited to: ongoing or active infection; altered mental status or psychiatric illness/social situations that would limit compliance with study requirements and/or obscure study results.
- Uncontrolled systemic vascular hypertension (systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg on medication).
- Patients with clinically significant cardiovascular disease: history of cardiovascular accident (CVA) within 6 months, myocardial infarction or unstable angina within 6 months, or unstable angina pectoris.
- Patients with colorectal carcinoma with tumors that demonstrate a Kirsten rat sarcoma (KRAS) mutation.
- Pregnant or lactating women.
- Patients with a history of bone marrow transplant within the previous two years.
Show all 9Show fewer
- Patients with a known hypersensitivity to any of the components of the drug products.
- Patients unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with proper absorption of oral drugs.
- Patients with major surgery within 30 days prior to entering the study.
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 I Dose-Escalation Study of Erlotinib in Combination With Bortezomib in Subjects With Advanced Cancer. Companion Study to Umbrella Protocol 2007-0638.
The goal of this clinical research study is to find the highest tolerable dose of Tarceva (erlotinib hydrochloride) that can safely be given in combination with Velcade (bortezomib). The safety of this drug combination will also be studied.
Read the detailed description
The Study Drugs:
Erlotinib hydrochloride and bortezomib are both designed to block proteins that are thought to cause cancer cells to grow. These drugs may help slow the growth of tumors.
Study Drug Dose Level:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of erlotinib hydrochloride and bortezomib based on when you join the study. Up to 4 dose levels of this study drug combination will be tested. There will be 3-6 participants enrolled at each dose level of the study drug combination.
The first group of participants will receive the lowest dose level of erlotinib hydrochloride (Group 1). If all of Group 1 tolerate that dose level, the next group (Group 2) will receive a higher dose. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen (Groups 2-4). This will continue until the highest tolerable dose of the study drug combination is found. However, if Group 1 did not tolerate the first dose level, the next group will receive a lower dose (called Dose Level -1). If that dose level is still intolerable, the third group will receive an even lower dose (called Dose Level -2).
The dose of bortezomib will be based in which group you in. Groups 1 and 2 will receive the same dose, Group 3 will receive a higher dose, and Group 4 will receive an even higher dose.
After the highest tolerable dose is found, up to an additional 10 participants, called the "expansion group," will receive the study drug combination at that dose.
Study Drug Administration:
Erlotinib hydrochloride will be taken by mouth 1 time every day for 21-days, called a study "cycle." You should take erlotinib hydrochloride on an empty stomach either 1 hour before eating or 2 hours after eating.
Depending on which dose level you are assigned to, you will receive bortezomib by vein over about 1-5 minutes on Days 1 and 8, or on Days 1, 4, 8, and 11 of each 21-day cycle.
Study Visits:
You will have a single study visit just before each cycle. At these visits, the following tests and procedures will be performed:
- Your performance status will be recorded.
- You will be asked to list any drugs you may be taking, including over-the-counter drugs.
- You will be asked about any symptoms you may have.
- You will have a physical exam, including measurement of your vital signs.
- Blood (about 2 teaspoons) will be collected for routine tests.
- Blood (about 2 teaspoons) will be collected for pharmacodynamic (PD) testing. PD testing is used to look at how the level of study drug in your body may affect the disease.
After every 2 cycles (Cycles 2, 4, 6, and so on), you will have a CT or MRI scan to check the status of the disease.
Length of Study:
You may continue taking the study drugs for as long as you are benefitting. You will be taken off study if the disease gets worse or intolerable side effects occur.
Follow-up Visit:
About 30 days after the last dose of study drugs, you will have a follow-up visit. You will be asked to return any unused study drug. At this visit, the following tests and procedures will be performed:
- Your performance status will be recorded.
- You will be asked to list any drugs you may be taking, including over-the-counter drugs.
- You will be asked about any symptoms you may have.
- You will have a physical exam, including measurement of your vital signs.
- Blood (about 2 teaspoons) and urine will be collected for routine tests.
This is an investigational study. Bortezomib and erlotinib hydrochloride are both FDA approved and commercially available. Bortezomib is FDA approved for the treatment of multiple myeloma. Erlotinib hydrochloride is FDA approved for the treatment of lung cancer and pancreatic cancer. The use of these drugs together is investigational and authorized for use in research only.
Up to 48 participants will take part in this study. All will be enrolled at M. D. Anderson.
- Conditions
- Advanced Cancer
- Being tested
- Erlotinib Hydrochloride, Bortezomib
- Keywords
- Metastatic Cancer, Bortezomib, Velcade, Erlotinib, Erlotinib Hydrochloride, Tarceva, EGFR, EGFR mutations
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Erlotinib HydrochlorideDrug
Also called Erlotinib, Tarceva
Beginning dose of 150 mg taken by mouth daily for 21-day cycle.
BortezomibDrug
Also called Velcade, LDP-341, MLN341, PS-341
Beginning dose of 1. mg/m^2 by vein over about 1-5 minutes on Days 1, 4, 8, and 11 of each 21-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Erlotinib + Bortezomib | Experimental | Up to 4 dose levels of study drug combination tested with 3-6 participants enrolled at each dose level. Erlotinib beginning dose of 150 mg taken by mouth daily for 21-day cycle. Bortezomib beginning dose of 1. mg/m^2 by vein over about 1-5 minutes on Days 1, 4, 8, and 11 of each 21-day cycle. Receives: Drug: Erlotinib Hydrochloride; Drug: Bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Response
Tumor response defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, (3) decrease in tumor markers by more than or equal to 25% (for example, a >/= 25% decrease in cancer antigen 125 (CA125) for patients with ovarian cancer), or (4) a partial response according to the Choi criteria, i.e. decrease in size by 10% or more, or a decrease in the tumor density, as measured in Hounsfield units (HU), by more than or equal to 15%.
Measured: Evaluation of response after two 21-day cycles of treatment
Maximum Tolerated Dose (MTD)
MTD defined as highest dose studied in which incidence of dose limiting toxicity (DLT) was less than 33%. DLT defined as any Grade 3 or 4 non-hematologic toxicity defined in the NCI CTC v3.0, even if expected and believed related to study medications (except nausea and vomiting responsive to appropriate regimens or alopecia), any Grade 4 hematologic toxicity lasting 2 weeks or longer (as defined by the NCI-CTCAE), despite supportive care; 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-CTCAE that is attributable to the therapy.
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2009 (estimated)
- Study startApr 2009
- Primary completionJul 2015
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
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jennifer J. Wheler, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00895687
- Sponsor's protocol ID
- 2008-0554
- Other IDs
- NCI-2012-01631
- Status last verified
- Jul 2015
- First submitted
- 6 May 2009
- Last updated
- 13 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose-Escalation Study of Erlotinib in Combination With Bortezomib in Subjects With Advanced Cancer. Companion Study to Umbrella Protocol 2007-0638.
- ClinicalTrials.gov ID
- NCT00895687
- Acronym / sponsor ID
- 2008-0554
- Conditions
- Advanced Cancer
- Keywords
- Metastatic Cancer, Bortezomib, Velcade, Erlotinib, Erlotinib Hydrochloride, Tarceva, EGFR, EGFR mutations
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Apr 2009
- Primary completion
- Jul 2015 (actual)
- First posted
- 8 May 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 Tarceva (erlotinib hydrochloride) that can safely be given in combination with Velcade (bortezomib). The safety of this drug combination will also be studied.
Detailed description
The Study Drugs:
Erlotinib hydrochloride and bortezomib are both designed to block proteins that are thought to cause cancer cells to grow. These drugs may help slow the growth of tumors.
Study Drug Dose Level:
If you are found to be eligible to take part in this study, you will be assigned to a dose level of erlotinib hydrochloride and bortezomib based on when you join the study. Up to 4 dose levels of this study drug combination will be tested. There will be 3-6 participants enrolled at each dose level of the study drug combination.
The first group of participants will receive the lowest dose level of erlotinib hydrochloride (Group 1). If all of Group 1 tolerate that dose level, the next group (Group 2) will receive a higher dose. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen (Groups 2-4). This will continue until the highest tolerable dose of the study drug combination is found. However, if Group 1 did not tolerate the first dose level, the next group will receive a lower dose (called Dose Level -1). If that dose level is still intolerable, the third group will receive an even lower dose (called Dose Level -2).
The dose of bortezomib will be based in which group you in. Groups 1 and 2 will receive the same dose, Group 3 will receive a higher dose, and Group 4 will receive an even higher dose.
After the highest tolerable dose is found, up to an additional 10 participants, called the "expansion group," will receive the study drug combination at that dose.
Study Drug Administration:
Erlotinib hydrochloride will be taken by mouth 1 time every day for 21-days, called a study "cycle." You should take erlotinib hydrochloride on an empty stomach either 1 hour before eating or 2 hours after eating.
Depending on which dose level you are assigned to, you will receive bortezomib by vein over about 1-5 minutes on Days 1 and 8, or on Days 1, 4, 8, and 11 of each 21-day cycle.
Study Visits:
You will have a single study visit just before each cycle. At these visits, the following tests and procedures will be performed:
- Your performance status will be recorded.
- You will be asked to list any drugs you may be taking, including over-the-counter drugs.
- You will be asked about any symptoms you may have.
- You will have a physical exam, including measurement of your vital signs.
- Blood (about 2 teaspoons) will be collected for routine tests.
- Blood (about 2 teaspoons) will be collected for pharmacodynamic (PD) testing. PD testing is used to look at how the level of study drug in your body may affect the disease.
After every 2 cycles (Cycles 2, 4, 6, and so on), you will have a CT or MRI scan to check the status of the disease.
Length of Study:
You may continue taking the study drugs for as long as you are benefitting. You will be taken off study if the disease gets worse or intolerable side effects occur.
Follow-up Visit:
About 30 days after the last dose of study drugs, you will have a follow-up visit. You will be asked to return any unused study drug. At this visit, the following tests and procedures will be performed:
- Your performance status will be recorded.
- You will be asked to list any drugs you may be taking, including over-the-counter drugs.
- You will be asked about any symptoms you may have.
- You will have a physical exam, including measurement of your vital signs.
- Blood (about 2 teaspoons) and urine will be collected for routine tests.
This is an investigational study. Bortezomib and erlotinib hydrochloride are both FDA approved and commercially available. Bortezomib is FDA approved for the treatment of multiple myeloma. Erlotinib hydrochloride is FDA approved for the treatment of lung cancer and pancreatic cancer. The use of these drugs together is investigational and authorized for use in research only.
Up to 48 participants will take part in this study. All will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Erlotinib + Bortezomib | Experimental | Drug: Erlotinib Hydrochloride, Drug: BortezomibUp to 4 dose levels of study drug combination tested with 3-6 participants enrolled at each dose level. Erlotinib beginning dose of 150 mg taken by mouth daily for 21-day cycle. Bortezomib beginning dose of 1. mg/m^2 by vein over about 1-5 minutes on Days 1, 4, 8, and 11 of each 21-day cycle. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Patients with pathologically confirmed advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have had no standard therapy that induces a CR rate of at least 10% or improves survival by at least three months.
- Measurable or non-measurable disease.
- Patients must be >/= 6 wks beyond treatment with a nitrosourea or mitomycin-C, >/= 4 wks beyond other chemotherapy or external beam radiation therapy (XRT), and must have recovered to </= Grade 1 toxicity for any treatment-limiting toxicity resulting from prior therapy. (Exception: patients may have received palliative low dose XRT one week before treatment provided it is not given to the only targeted lesions).
- (continued from above) Also, patients who have received non-chemotherapeutic biological agents will need to wait at least 5 half-lives or 4 wks, whichever is shorter, from the last day of treatment.
- Eastern Cooperative Oncology Group (ECOG) performance status </= 2 (Karnofsky >/= 60%)
Key exclusion criteria (9 listed)
- Patients with uncontrolled concurrent illness, including but not limited to: ongoing or active infection; altered mental status or psychiatric illness/social situations that would limit compliance with study requirements and/or obscure study results.
- Uncontrolled systemic vascular hypertension (systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg on medication).
- Patients with clinically significant cardiovascular disease: history of cardiovascular accident (CVA) within 6 months, myocardial infarction or unstable angina within 6 months, or unstable angina pectoris.
- Patients with colorectal carcinoma with tumors that demonstrate a Kirsten rat sarcoma (KRAS) mutation.
- Pregnant or lactating women.
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 |
|---|---|---|
| Erlotinib HydrochlorideAlso: Erlotinib, TarcevaBeginning dose of 150 mg taken by mouth daily for 21-day cycle. | Drug | Erlotinib + Bortezomib |
| BortezomibAlso: Velcade, LDP-341, MLN341, PS-341Beginning dose of 1. mg/m^2 by vein over about 1-5 minutes on Days 1, 4, 8, and 11 of each 21-day cycle. | Drug | Erlotinib + Bortezomib |
Primary outcome
Tumor Response
Time frame: Evaluation of response after two 21-day cycles of treatment
Tumor response defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, (3) decrease in tumor markers by more than or equal to 25% (for example, a >/= 25% decrease in cancer antigen 125 (CA125) for patients with ovarian cancer), or (4) a partial response according to the Choi criteria, i.e. decrease in size by 10% or more, or a decrease in the tumor density, as measured in Hounsfield units (HU), by more than or equal to 15%.
Maximum Tolerated Dose (MTD)
Time frame: 21 days
MTD defined as highest dose studied in which incidence of dose limiting toxicity (DLT) was less than 33%. DLT defined as any Grade 3 or 4 non-hematologic toxicity defined in the NCI CTC v3.0, even if expected and believed related to study medications (except nausea and vomiting responsive to appropriate regimens or alopecia), any Grade 4 hematologic toxicity lasting 2 weeks or longer (as defined by the NCI-CTCAE), despite supportive care; 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-CTCAE that is attributable to the 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 13 Jul 2015.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
Related trials for Advanced Cancer
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
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.
Jennifer J. Wheler, 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 Erlotinib Hydrochloride and Bortezomib 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 9 inclusion and 9 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 13 Jul 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?
Tumor Response (time frame: Evaluation of response after two 21-day cycles of treatment). The study lists 2 primary outcomes in all. 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 13 Jul 2015.