A Phase I Dose-Escalation Study of Erlotinib in Combination With Pralatrexate in Subjects With Advanced Cancer
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose
level of erlotinib and pralatrexate based on when you join this study.
Dose Escalation:
Several dose levels of erlotinib and pralatrexate will be tested. Three (3) to 6
participants will start at the lowest planned doses of erlotinib and pralatrexate. Each new
group of 3-6 participants 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
erlotinib in combination with pralatrexate is found.
Dose Expansion:
Once the highest tolerable dose or most appropriate combination dose level is found, 10 more
participants will take the study drugs at this dose level.
Study Drug Administration:
Each study cycle is 28 days.
Up to 10 days before you start treatment , you will start taking folic acid to help lower
the risk of side effects. Although the study drug is designed to prevent the body from
making folic acid that could help cancer grow and spread, some folic acid is needed to
prevent side effects in non-cancerous tissue. You will take folic acid by mouth 1 time
every day during treatment and for at least 30 days after you received the last dose of
pralatrexate.
Up to 10 days before you start treatment, you will receive a vitamin B12 injection. You will
receive an injection of Vitamin B12 about every 3 months after that.
On Days 1, 8, and 15 of each cycle, you will receive pralatrexate by vein over 3-5 minutes.
You will take erlotinib hydrochloride by mouth 1 time a day every day. You should take
erlotinib hydrochloride on an empty stomach either 1 hour before eating or 2 hours after
eating.
You will take erlotinib at home except on the days when you have a study visit. You should
take it at about the same time each day with about a cup (8 ounces) of water.
Study Visits:
At every study visit, you will be asked about any current health conditions you have, any
other drugs you are taking, and if you have had any side effects.
If the screening tests were performed within 7 days before Cycle 1, tests and procedures may
not have to be repeated.
At any time during Cycle 1:
- You will have a physical exam, including measurement of your weight at least 1 time per
cycle.
- Your vital signs will be measured.
- Your performance status will be recorded.
- Blood (about 2 teaspoons) will be drawn for routine tests and to see how well your
blood clots.
- If you are taking part in the expansion phase, blood (about 2 teaspoons) will be drawn
for PD testing.
At any time during Cycle 2:
- You will have a physical exam, including measurement of your weight at least 1 time per
cycle.
- Your vital signs will be measured.
- Your performance status will be recorded.
- Blood (about 4 teaspoons) will be drawn for routine tests.
- If you are taking part in the expansion phase, blood (about 2 teaspoons) will be drawn
for PD testing.
About every 8 weeks, you will have an x-ray, CT scan, MRI scan, and/or PET/CT scan to check
the status of the disease. Blood (about 1 teaspoon) may be drawn for tumor marker testing
depending on the type of tumor. If the study doctor thinks it is needed, they will be
performed more or less often.
At any time during Cycle 3 and beyond:
- You will have a physical exam, including measurement of your weight at least 1 time per
cycle.
- Your vital signs will be measured.
- Your performance status will be recorded.
- Blood (about 2 teaspoons) will be drawn for routine tests.
Length of Dosing:
You may continue taking the study drugs for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the study drugs if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over once you have completed the end-of-treatment
and follow-up visits.
End of Dosing Visit:
After you are finished taking the study drugs:
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 2 teaspoons) and urine will be collected for routine tests.
This is an investigational study. Pralatrexate is FDA approved and commercially available
for the treatment of cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma
(PTCL). Erlotinib is FDA approved and commercially available for the treatment of pancreatic
cancer and non small cell lung cancer (NSCLC). The study drug combination is
investigational.
Up to 74 patients will take part in this study. All will be enrolled at MD Anderson.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD)
MTD defined by dose limiting toxicities (DLTs) that occur in the first cycle. DLT defined as any Grade 3 or 4 non-hematologic toxicity as defined in the NCI CTC v3.0. Grade 4 hematologic toxicity lasting 2 weeks or longer despite supportive care. 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 therapy.
8 weeks
Yes
Jennifer J. Wheler, MD
Principal Investigator
UT MD Anderson Cancer Center
United States: Food and Drug Administration
2011-0916
NCT01532011
March 2012
Name | Location |
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UT MD Anderson Cancer Center | Houston, Texas 77030 |