Clinical trial NCT01407198: Nilotinib With Radiation for High Risk Chordoma
Official title: Phase I Study of Nilotinib Given With Radiation For Patients With High Risk Chordoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Chordoma
Keywords: High Risk Chordoma
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2011-08-02
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed chordoma
* Considered to have high risk disease
* Measurable disease
* Life expectancy \> 3 months
* Adequate organ function
* Able to swallow oral capsules

Exclusion Criteria:

* Previous treatment with any other tyrosine kinase inhibitor
* Previous treatment with radiotherapy to the primary or recurrent chordomas
* Impaired cardiac function
* Currently receiving treatment with strong CYP3A4 inhibitors
* Requires anticoagulation with coumadin
* Impaired GI function or GI disease that may significantly alter the absorption of study drug
* Acute or chronic pancreatic disease
* Known cytopathologically confirmed CNS infiltration
* Another primary malignant disease which requires systemic treatment
* Acute or chronic liver disease or severe renal disease considered unrelated to the cancer
* History of significant congenital or acquired bleeding disorder unrelated to cancer
* Major surgery within 4 weeks prior to Day 1 of the study or who have not recovered from prior surgery
* Treatment with other investigational agents within 30 days of Day 1
* History of non-compliance to medical regimens
* Pregnant or breast-feeding

Primary outcomes:
measure: To determine the dose limiting toxicities (DLTs) for participants when treated above the maximum tolerated dose (MTD).
timeFrame: 2 years
Secondary outcomes:
measure: Number of Participants with Adverse Events
timeFrame: 2 years
measure: Survival
timeFrame: 2 years
measure: PDGFR signaling
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Edwin Choy, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: