Nilotinib With Radiation for High Risk Chordoma
The study drug, Nilotinib, is believed to slow down tumor growth by regulating a gene involved in cellular growth of chordoma cells. During this research study, subjects will also receive radiation therapy which is considered a standard treatment for advanced chordomas. It is hoped by adding nilotinib, the benefits of radiation therapy can be enhanced without adding significant toxicities.
The purpose of this research study is to determine the safety of nilotinib when used in combination with radiation therapy, and the highest dose of nilotinib that can be given safely with radiation therapy.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Nilotinib Given With Radiation For Patients With High Risk Chordoma|
- To determine the dose limiting toxicities (DLTs) for participants when treated above the maximum tolerated dose (MTD). [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
A DLT will be defined as any of the following events occurring during days 1-56 of study according to CTCAE version 4.0. MTD is then determined by identifying a dose cohort demonstrating > or = 30% rate of DLTs, which are defined as:
- Any Grade ≥ 3 nonhematologic toxicity except alopecia, nausea, or vomiting not otherwise controlled by maximual supportive care.
- Grade 4 neutropenia (ANC < 500/µL) lasting > 5 days, Grade 3 thrombocytopenia lasting > 7 days, or Grade 4 thrombocytopenia
- Failure to resume treatment delays within a defined period of time.
- Number of Participants with Adverse Events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Adverse event profile, as determined by CTC AE version 4.0, will be determined for patients treated with nilotinib and radiation therapy.
Adverse events analyses will include:
- Detailed examination of adverse events
- Laboratory test results
- Vital signs or other physical findings
- Frequency and extent of dose modification
The assessment of adverse events will be based mainly on the frequency of adverse events, particularly adverse events leading to discontinuation of treatment and on the number of significant laboratory abnormalities.
- Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]To obtain preliminary data regarding local control, distant control, disease-free survival, and overall survival with this regimen
- PDGFR signaling [ Time Frame: 2 years ] [ Designated as safety issue: No ]To determine if nilotinib decreases PDGFR signaling in chordoma tumor samples in treated patients
|Study Start Date:||August 2011|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||July 2017 (Final data collection date for primary outcome measure)|
Nilotinib is administered 400mg PO BID for 2 weeks and then administered concurrently with daily XRT until completion of XRT. Participants can then undergo surgery if clinically possible. After either surgery or definitive radiation, participants have the option to continue on nilotinib therapy.
Orally, daily 200 - 400 mg BID
Other Names:Radiation: Radiation therapy
External beam radiation will be delivered at 1.8 Gy per day, 5 days per week (excluding holidays)for a total of 28 fractions over a 6 weeks period.
Other Name: External beam radiation
Nilotinib will be taken orally daily in two cycles of 28 days each. Two weeks after taking nilotinib, subjects will begin radiation therapy. Radiation therapy will continue every weekday until Day 56 of the study. If it is determined that the subject's tumor cannot be removed by surgery, an additional 3 weeks of radiation therapy will be applied after Day 56 of the study.
During study visits subjects will have physical exams, routine blood tests, urine and blood clotting tests, and EKGs. Subjects will also have tumor assessment by chest CT and MRI or CT of the tumor at screening, on approximately Day 56 of the study, then every 6 months for one year and then annually thereafter if ther is no disease progression.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01407198
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Edwin Choy, MD, PhD||Massachusetts General Hospital|