Nilotinib With Radiation for High Risk Chordoma

Phase I Study of Nilotinib Given With Radiation For Patients With 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 Overview

• Status: Active, not recruiting
• Conditions: Chordoma
• Intervention / Treatment: Drug: Nilotinib; Radiation: 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.

• Study Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nilotinib/XRT; 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.	Drug: Nilotinib; Orally, daily 200 - 400 mg BID; Other Names: AMN 107; Tasigna; 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 Names: External beam radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the dose limiting toxicities (DLTs) for participants when treated above the maximum tolerated dose (MTD).	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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events	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.	2 years
Survival	To obtain preliminary data regarding local control, distant control, disease-free survival, and overall survival with this regimen	2 years
PDGFR signaling	To determine if nilotinib decreases PDGFR signaling in chordoma tumor samples in treated patients	2 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Edwin Choy, MD, PhD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): February 1, 2016
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 28, 2011
• First Submitted That Met QC Criteria: July 29, 2011
• First Posted (Estimated): August 2, 2011

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 10, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: High Risk Chordoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Germ Cell and Embryonal; Chordoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Nilotinib
• Other Study ID Numbers: 11-072

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO