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Nilotinib With Radiation for High Risk Chordoma

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ClinicalTrials.gov Identifier: NCT01407198
Recruitment Status : Active, not recruiting
First Posted : August 2, 2011
Last Update Posted : March 12, 2024
Sponsor:
Information provided by (Responsible Party):
Edwin Choy, MD, Massachusetts General Hospital

Study Description
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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.


Condition or disease Intervention/treatment Phase
Chordoma Drug: Nilotinib Radiation: Radiation therapy Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Nilotinib Given With Radiation For Patients With High Risk Chordoma
Study Start Date : August 2011
Actual Primary Completion Date : February 2016
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Chordoma
Drug Information available for: Nilotinib

Arms and Interventions
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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 Name: External beam radiation


Outcome Measures
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Primary Outcome Measures :
  1. To determine the dose limiting toxicities (DLTs) for participants when treated above the maximum tolerated dose (MTD). [ Time Frame: 2 years ]

    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.


Secondary Outcome Measures :
  1. Number of Participants with Adverse Events [ Time Frame: 2 years ]

    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. Survival [ Time Frame: 2 years ]
    To obtain preliminary data regarding local control, distant control, disease-free survival, and overall survival with this regimen

  3. PDGFR signaling [ Time Frame: 2 years ]
    To determine if nilotinib decreases PDGFR signaling in chordoma tumor samples in treated patients


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01407198


Locations
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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
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Principal Investigator: Edwin Choy, MD, PhD Massachusetts General Hospital
More Information
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Responsible Party: Edwin Choy, MD, Instructor, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01407198    
Other Study ID Numbers: 11-072
First Posted: August 2, 2011    Key Record Dates
Last Update Posted: March 12, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Edwin Choy, MD, Massachusetts General Hospital:
High Risk Chordoma
Additional relevant MeSH terms:
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Chordoma
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Nilotinib
 Tyrosine Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action