Nilotinib With Radiation for High Risk Chordoma

Mass General Brigham

Status and phase: Completed; Phase 1

Conditions: Chordoma

Treatments: Radiation: Radiation therapy; Drug: Nilotinib

Study type: Interventional

Funder types: Other

Identifiers

NCT01407198

11-072

Details and patient eligibility

About

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.

Full 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.

Enrollment: 23 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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23 participants in 1 patient group

Nilotinib/XRT

Experimental group

Description:

Nilotinib is administered 400mg PO BID for 2 weeks and then administered concurrently with daily radiation therapy until completion of radiation therapy. Participants can then undergo surgery if clinically possible. After either surgery or definitive radiation, participants have the option to continue on nilotinib therapy.

Treatment:

Drug: Nilotinib

Radiation: Radiation therapy