A Phase I Dose-Escalation Study of Erlotinib in Combination With Cetuximab in Subjects With Advanced Cancer. Companion Study to Umbrella Protocol 2007-0638.
18 Years
N/A
Both
Advanced Cancers
Trial Information
A Phase I Dose-Escalation Study of Erlotinib in Combination With Cetuximab in Subjects With Advanced Cancer. Companion Study to Umbrella Protocol 2007-0638.
The Study Drugs:
Erlotinib and cetuximab are both designed to block a certain protein, called EGFR, that is
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 cetuximab 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 cetuximab will be based in which group you in. Groups 1-3 will receive the same
dose and Group 4 will receive a 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 28-days, called a study
"cycle." You should take erlotinib hydrochloride on an empty stomach either 1 hour before
eating or 2 hours after eating.
Cetuximab will be given by vein 1 time every week. The first time you receive cetuximab, it
will be given over 2 hours. Every time you receive cetuximab after that, it will be given
over 1 hour.
Study Visits:
You will have a single study visit just before the start 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 the first 2 cycles and then every 2 to 3 cycles, 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 drugs. 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. Cetuximab and Erlotinib hydrochloride are both FDA
approved and commercially available. Cetuximab is FDA approved for the treatment of
colorectal cancer and cancer of the head and neck. 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 MD Anderson.
Inclusion Criteria:
1. 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.
2. Measurable or non-measurable disease.
3. Patients must be >/= 6 wks beyond treatment with a nitrosourea or mitomycin-C, >/= 4
wks beyond other chemotherapy or XRT, and must have recovered to 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).
4. (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.
5. ECOG performance status /= 60%)
6. Patients must have normal organ and marrow function defined as: absolute neutrophil
count >/=1,000/mL; platelets >/=50,000/mL; creatinine bilirubin
7. 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.
8. Ability to understand and the willingness to sign a written informed consent document
9. 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]).
Exclusion Criteria:
1. 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.
2. Uncontrolled systemic vascular hypertension (systolic blood pressure > 140 mm Hg,
diastolic blood pressure > 90 mm Hg on medication).
3. Patients with clinically significant cardiovascular disease: history of CVA within 6
months, myocardial infarction or unstable angina within 6 months, or unstable angina
pectoris.
4. Patients with colorectal carcinoma with tumors that demonstrate a KRAS mutation.
5. Pregnant or lactating women.
6. Patients with a history of bone marrow transplant within the previous two years.
7. Patients with a known hypersensitivity to any of the components of the drug products.
8. Patients unable to swallow oral medications or with pre-existing gastrointestinal
disorders that might interfere with proper absorption of oral drugs.
9. Patients with major surgery within 30 days prior to entering the study.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum Tolerated Dose (MTD)
Outcome Description:
Continuous assessment of safety throughout entire study period and determination of MTD by dose-limiting toxicities during and at the end of 28 day cycle.
Outcome Time Frame:
With each 28 day cycle
Safety Issue:
Yes
Principal Investigator
Jennifer J. Wheler, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
2008-0553
NCT ID:
NCT00895362
Start Date:
April 2009
Completion Date:
Related Keywords:
- Advanced Cancers
- Advanced Cancer
- EGFR mutation
- Erlotinib
- Erlotinib Hydrochloride
- Tarceva
- OSI-774
- Cetuximab
- C225
- Erbitux
- IMC-C225
- Neoplasms
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
